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| Eur J Surg, 1998 Nov, 164(11), 825 - 9 Predictors of recurrence of fulminant bacterial peritonitis after discontinuation of antibiotics in open management of the abdomen; Visser MR et al.; OBJECTIVE: To assess a scoring system for predicting recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial treatment in patients being treated by open management of the abdomen for persistent bacterial peritonitis after perforation of the digestive tract, anastomotic disruption, or necrotising pancreatitis . DESIGN: Retrospective study . SETTING: University Hospital, The Netherlands . SUBJECTS: 58 consecutive patients . MAIN OUTCOME MEASUREMENTS: Recurrence of fulminant bacterial peritonitis and survival . RESULTS: 13 of the 58 patients (22%) died during the initial course of antimicrobial drugs . 14 of the remaining 45 patients had a recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial drugs, 4 of whom died . Predictive criteria included raised white cell count (WCC) (p = 0.02), duration of initial antibiotic treatment (p = 0.05), and deterioration in Simplified Acute Physiology Score (p = 0.05) . Using the WCC and the duration of initial antimicrobial treatment together with other variables that showed a predictive trend (body temperature, percentage band cells, underlying disease, and use of inotropic agents), in a new scoring system (0-12), fulminant bacterial peritonitis did not recur when the score was 0-3, but in 9 of 11 patients with a score of 6 or more it did (p < 0.001) . CONCLUSION: Patients at increased risk of recurrence of fulminant bacterial peritonitis during open management of the abdomen can be identified at the time of discontinuation of antimicrobial treatment by a new scoring system; antimicrobial treatment should not be discontinued in patients with a score of 6 or more. Int J Radiat Oncol Biol Phys, 1998 Nov 1, 42(4), 755 - 62 Bioreductive therapies: an overview of drugs and their mechanisms of action; Rauth AM et al.; PURPOSE: Bioreductively activated drugs have been used as antimicrobials, chemotherapeutic agents, and radiation sensitizers . The present paper is an overview of their mechanism of action and application in the treatment of cancer . MATERIALS AND METHODS: Drugs such as nitroimidazoles, mitomycins, and benzotriazine di-N-oxides were a focus of this research . Studies have ranged from the chemistry of the reductive process of activation to in vitro and in vivo studies in rodent and human cells, through to clinical testing . The variety of techniques and test systems brought to bear on these compounds is a strength of this field of research . RESULTS: A detailed chemical understanding of the mechanism of action of a variety of bioreductives is now available . The enzymatic processes by which these drugs are activated and the cofactors involved in this activation are becoming well understood . Recent advances have been made in the design and use of dual-function bioreductives, bioreductive triggers of drug activation, and DNA-targeted bioreductives . Significant success has been demonstrated clinically with bioreductive drugs, used in combination with radiation and front-line chemotherapeutic agents . The areas of antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) are identified as new directions for bioreductive therapy . CONCLUSION: The use of bioreductively-activated drugs for the treatment of cancer has made steady progress . The success obtained clinically and the new molecular approaches currently being implemented promise significant advances in the future. Intensive Care Med, 1998 Oct, 24(10), 1106 - 9 Sweet's syndrome associated with systemic inflammatory response syndrome; Matthews PC et al.; Septic shock is characterised by infection causing a systemic inflammatory response, end-organ failure and acute circulatory collapse . Treatment consists of antimicrobial therapy and the supportive management of multi-organ failure . We report a case of what we believed to be septic shock due to pyelonephritis in a patient whose condition continued to deteriorate despite conventional treatment until the diagnosis of Sweet's syndrome was made . Once she was started on high dose steroids, her condition improved and she made a full recovery . We believe this to be the first case of a severe systemic inflammatory response syndrome associated with Sweet's syndrome. J Gastroenterol, 1998, 33 Suppl 10, 57 - 61 Eradication therapy of Helicobacter pylori . A review . Report from a workshop organized by the Swedish and Norwegian Medical Products Agencies, September 1995; Unge P; An expert meeting was organized by the Swedish and Norwegian Medical Products Agencies in September 1995 in order to review the current literature and opinions on detection and treatment of Helicobacter pylori . Ten people from these Agencies and 23 experts participated in the workshop and all were involved in the final manuscript, summarizing the background data and the conclusions (Info Lakemedelsverket 1:96) . This report is limited to the therapeutic issues . Therapeutic effect on H . pylori is shown for tetracyclines, nitroimidazoles, clarithromycin, and amoxicillin . Acid inhibitory drugs or bismuth salts increase the antibacterial activity . In vitro resistance to metronidazole is reported in cultures of 10%-40% of H . pylori-infected patients in Scandinavia . Primary resistance to clarithromycin and tetracyclines is rare and no resistance to amoxicillin is confirmed . The clinical significance of resistance is unclear when effective triple combinations are used in previously untreated patients, but should be considered in treatment failures . Recommended therapeutic regimens should achieve a more than 90% cure rate . Important factors when choosing therapy are efficacy, side-effects, ecological factors, duration of therapy, and cost-benefit . Four triple regimens are effective and relatively well documented: omeprazole/amoxicillin/metronidazole for 1 week, omeprazole/clarithromycin/metronidazole for 1 week, omeprazole/clarithromycin/amoxicillin for 1 week, or bismuth subnitrate or bismuth citrate/tetracycline/metronidazole for 10 days . Side-effects are less pronounced in the combinations without bismuth . Dual therapy is not recommended . Eradication therapy should be considered for patients with peptic ulcer disease, MALT-lymphoma and Menetriere's disease . Triple combinations, including two antimicrobials and a potent acid inhibitory drug or bismuth, are recommended. J Immunol Methods, 1998 Nov 1, 220(1-2), 123 - 8 A method to assess invasion and intracellular replication of Trypanosoma cruzi based on differential uracil incorporation; Yan W et al.; Screening of candidate trypanocidal compounds or factors affecting invasion of mammalian cells by the infective stages of Trypanosoma cruzi in tissue culture models has primarily involved labor-intensive microscopic counting of the parasites . A very efficient method for quantitating the inhibitory effect of antimicrobial agents or signaling pathways inhibitors on T . cruzi grown in L6E9 myoblasts was devised . This assay takes advantage of the selective incorporation of {3H}uracil into nucleic acids by replicating T . cruzi amastigotes . L6E9 rat myoblasts are submitted to gamma irradiation to inhibit their replication . Uracil uptake by uninfected cells is considerably decreased by this method . Nifurtimox, benznidazole, fexinidazole, MK-436, and megazol are drugs known to have activity against T . cruzi and were used in growth inhibition assays . The results demonstrated that {3H}uracil incorporation in the presence of different concentrations of nifurtimox and benznidazole closely correlated with the number of amastigotes per 100 myoblasts in Giemsa-stained monolayers under the conditions used . This method also has the advantage to differentiate between the effects of the compounds on the invasion and the replication steps of the infection with T . cruzi, as shown by the inhibitory effect of genistein when added in invasion assays. J Clin Periodontol, 1998 Nov, 25(11 Pt 2), 959 - 63; discussion 978-9 The use of locally delivered metronidazole in the treatment of periodontitis . Clinical results; Magnusson I; Local delivery of antimicrobials has been investigated as a possible method for controlling and treating periodontal disease . A number of antimicrobial agents have been studied both as adjunctive therapies with scaling and root planing and as stand-alone chemotherapies . More recent investigations have focussed on the delivery of antimicrobials in sustained-release formulations designed to maintain effective concentrations of drug within the periodontal pocket . This article provides an overview of the development of the use of locally-delivered metronidazole in periodontal therapy and the current state-of-the-art of the technique . It is concluded that treatment with local delivery of metronidazole seems to be as effective as scaling and root planing in untreated as well as in recall subjects . However, there are reasons to suggest that local delivery of metronidazole should not be used as a substitute for conventional treatment of periodontal disease, since side-effects of long-term use and repeated use are not known . The antibiotic regimen should preferably be used as an adjunct to surgical and non-surgical therapy. J Clin Periodontol, 1998 Nov, 25(11 Pt 2), 943 - 6; discussion 978-9 Local delivery of chemotherapeutic agents in periodontal therapy: has its time arrived? Finkelman RD, Williams RC. The concept of locally delivering chemotherapeutic agents to the periodontal pocket as a method to treat periodontal disease has been studied for over 20 years . A number of locally delivered chemotherapeutic agents in periodontal therapy are either currently available or under investigation . Clinical efficacy derives from sustained-release technology to maintain an effective concentration of drug within the periodontal pocket for a clinically relevant length of time . Studied drugs have mainly been antimicrobials, both antibiotics and antiseptics . Most agents have been tested as adjuncts to scaling and root planing; a few have been studied as stand-alone monotherapies . Collectively, the data indicate that the use of locally delivered antimicrobials as adjuncts results in a significant increase in the reduction of probing depth compared with scaling and root planing alone . In other trials, results in reducing probing depth following the use of stand-alone locally delivered antimicrobials have been equivalent to those of scaling and root planing over a specified time . This Symposium was organized to present the current state-of-the-art with regard to the use of locally delivered antimicrobials in the treatment of periodontal disease . 5 experts in the field who have had considerable experience in studying locally delivered antimicrobials presented data . These speakers reviewed the clinical findings regarding efficacy of 5 different antimicrobial agents . An ensuing panel discussion was to consider treatment recommendations for locally delivered antimicrobials. Int J Epidemiol, 1998 Oct, 27(5), 904 - 8 Topical antimicrobials applied to the umbilical cord stump: a new intervention against neonatal tetanus; Parashar UD et al.; BACKGROUND: Previous case-control studies of neonatal tetanus (NNT), a leading cause of infant mortality in developing countries, have suggested that antimicrobials applied after delivery to the umbilical cord stump may protect against this disease . However, assessment of their protective effect has been limited by the low prevalence of antimicrobial use in developing countries . METHODS: We conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh . We studied 359 cases (infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT), each matched to three living controls for gender, residence, and date of birth . RESULTS: In univariate analyses, the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants were protective against NNT . The application of antibiotics at delivery (odds ratio {OR} = 0.21, P = 0.019), hand washing by the delivery attendant (OR = 0.64, P = 0.005), and prior maternal immunization with tetanus toxoid (OR = 0.50, P < 0.001) remained protective in conditional logistic-regression analyses . Application of animal dung to the umbilical stump (OR = 2.31, P = 0.047) was hazardous . CONCLUSIONS: Effective and inexpensive topical antimicrobials provide a new prevention opportunity that could be used by traditional birth attendants and mothers to provide additional benefits to NNT control programmes based on maternal immunization with tetanus toxoid . Promotion of hygienic delivery and cord-care practices and increasing tetanus toxoid coverage remain cornerstones for the prevention of NNT deathsPIP: Neonatal tetanus (NNT) is a leading cause of infant mortality in developing countries . Findings from previous case-control studies of NNT have suggested that antimicrobials applied following delivery to the umbilical cord stump may protect against the disease . However, assessment of their protective effect has been hampered by the low prevalence of antimicrobial use in developing countries . The authors conducted a population-based, matched, case-control study to assess the use of antimicrobials and other factors potentially related to NNT in rural parts of Bangladesh . 359 cases were studied, infants who were normal at birth but who died between the 3rd and 30th day of life after an illness characterized by signs of NNT . Each case was matched to 3 living controls for gender, residence, and date of birth . Univariate analyses found the application of either antibiotics or disinfectants at delivery, and the continuous or any application of disinfectants to protect against NNT . The application of antibiotics at delivery, hand washing by the delivery attendant, and prior maternal immunization with tetanus toxoid remained protective in conditional logistic-regression analyses . The application of animal dung to the umbilical stump was hazardous . Farmaco, 1998 Jul 30, 53(7), 462 - 7 Synthesis, structure elucidation and antimicrobial activity of some 3-hydroxy-2-naphthoic acid hydrazide derivatives; Dogan HN et al.; In this study, some 1,4-disubstituted thiosemicarbazide, 1,2,4-triazole and 1,3,4-thiadiazole type novel compounds derived from 3-hydroxy-2-naphthoic acid hydrazide were synthesized to screen for their antimicrobial activity . The structures of these substances were elucidated using elemental analysis and UV, 1H NMR, and mass spectral methods . All of these compounds were tested in vitro for their antibacterial and antifungal activity. Farmaco, 1998 Jul 30, 53(7), 455 - 61 Synthesis of substituted 2-ethoxycarbonyl- and 2-carboxyquinoxalin-3-ones for evaluation of antimicrobial and anticancer activity; Sanna P et al.; A series of variously substituted quinoxalin-3-ones bearing an ethoxycarbonyl or carboxy group in the C-2 position has been prepared and their structures proved by 1H NMR spectroscopy . The obtained compounds were investigated in vitro for antimicrobial and anticancer activities . Preliminary results showed a moderate activity against a few strains of bacteria but no significant anticancer and anti-HIV activity. Rev Port Cardiol, 1998 Oct, 17 Suppl 2, II41 - 6 Molecular mechanisms of arrhythmias; Janse MJ et al.; Most arrhythmias occur in patients with structural heart disease, where anatomical factors play an important role . Patients without structural heart disease may also suffer from arrhythmias, and recently the genetic basis for such so-called idiopathic arrhythmias has been elucidated . In the congenital long QT syndrome, characterized by a prolonged QT interval, torsade de pointes and sudden death, three aberrant ionic currents have been identified, resulting in a prolongation of the ventricular action potential, which in its turn may cause early afterdepolarization and torsade de pointes . In LQTS1, mutations in the KvLQT1 gene reduce the slow component of the delayed rectifier Iks; in LQTS, mutations in the Human Ether a-go-go Related Gene (HERG) reduce the rapid component of the delayed rectifier Iks . Both potassium currents are important determinants of repolarization: a reduction in outward currents carried by K+ ions prolongs the action potential . In LQTS3, there are mutation in the NA+ channel gene (SCN5A) which causes the channel to inactivate incompletely; the persistent inward current carried by Na+ ions also prolongs the action potential . In the Brugada syndrome, characterized by right bundle branch block, ST elevation in V1-V3 and sudden death, mutations have been observed in the Na+ channel gene, but it is as yet unclear which functional changes in the NA+ channel are responsible for the typical ECG changes and the arrhythmias . Various cardiac disorders may lead to changes in gene expression that modify channel function . In hypertrophy, the ventricular action potential is prolonged by a decrease in the inward rectifier and the transient outward current . After prolonged episodes of rapid electrical activity, the atrial action potential is shortened, because of a reduction in the Iks type calcium current . Finally, many carriers of mutated genes display no abnormalities on the ECG . It is conceivable that such individuals may show excessive QT prolongation when taking cardiac or noncardiac drugs (such as neuroleptics, antidepressants, antihistamines, antimicrobials, antimalarials) that block potassium currents. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3245 - 50 Induction of resistance to azole drugs in Trypanosoma cruzi; Buckner FS et al.; Trypanosoma cruzi is the protozoan parasite that causes Chagas' disease, a frequently fatal illness affecting the heart and gastrointestinal systems . An estimated 16 million to 18 million people in Latin America and 50,000 to 100,000 people in the United States are infected with this pathogen . Treatment options for T . cruzi infections are suboptimal due to the toxicities and limited effectiveness of the available drugs . Azole antimicrobial agents have been discovered to have antitrypanosomal activity by inhibition of ergosterol synthesis . The triazole itraconazole was recently shown to produce a parasitologic cure rate of 53% in chronically infected patients (W . Apt et al., Am . J . Trop . Med . Hyg . 59:133-138, 1998), a result which may lead to more use of this family of drugs for the treatment of T . cruzi infections . In the experiments reported on here, resistance to azoles was induced in vitro by serial passage of mammalian-stage parasites in the presence of fluconazole for 4 months . These parasites were cross resistant to the other azoles, ketoconazole, miconazole, and itraconazole . They remained susceptible to benznidazole and amphotericin B . The azole-resistant phenotype was stable for more than 2 months of in vitro serial passage without fluconazole . In addition, the parasites resisted treatment in mice receiving ketoconazole . The rapid development of azole resistance in T . cruzi in vitro suggests that resistance to azole drugs has the potential to occur in patients and may pose an impediment to the progress being made in the treatment of T . cruzi infection. Boll Chim Farm, 1998 Sep, 137(8), 321 - 4 Synthesis and antimicrobial activity of N-Mannich bases of 3-{N'-sulphadoximino} isatin and its methyl derivative; Surendra et al.; Schiff's bases of isatin and 5-methyl isatin with sulphadoxine and then its N-Mannich bases were synthesised and evaluated for their anti-microbial activity . The piperidonemethyl group improved the activity and most of the compounds were more potent than the pure drugs. J Nat Prod, 1998 Nov, 61(11), 1337 - 9 New macrodiolide antibiotics, 11-O-monomethyl- and 11, 11'-O-dimethylelaiophylins, from Streptomyces sp . HKI-0113 and HKI-0114; Ritzau M et al.; Elaiophylin (1) and two new methyl derivatives, 11-O-monomethylelaiophylin (2) and 11,11'-O-dimethylelaiophylin (3), were isolated from the mycelium cake of Streptomyces strains HKI-0113 and HKI-0114 . The structures of 2 and 3 were determined by mass spectrometric and NMR investigations . Compounds 2 and 3 display antimicrobial and moderate cytotoxic activities. Ann Emerg Med, 1998 Dec, 32(6), 703 - 11 EMERGEncy ID NET: an emergency department-based emerging infections sentinel network . The EMERGEncy ID NET Study Group; Talan DA et al.; Acute infectious disease presentations among many at-risk patient groups (eg, uninsured, homeless, and recent immigrants) are frequently seen in emergency departments . Therefore EDs may be useful sentinel sites for infectious disease surveillance . This article describes the background, development, and implementation of EMERGE ncy ID NET, an interdisciplinary, multicenter, ED-based network for research of emerging infectious diseases . EMERGE ncy ID NET was established in cooperation with the National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC) as part of the CDC's strategy to expand and complement existing disease detection and control activities . The network is based at 11 university-affiliated, urban hospital EDs with a combined annual patient visit census of more than 900,000 . Data are collected during ED evaluation of patients with specific clinical syndromes, and are electronically stored, transferred, and analyzed at a central receiving site . Current projects include investigation of bloody diarrhea and the prevalence of Shiga toxin-producing Escherichia coli, animal exposures and rabies postexposure prophylaxis practices, seizures and prevalence of neurocysticercosis, nosocomial ED Mycobacterium tuberculosis transmission, and hospital isolation bed use for adults admitted for pneumonia or suspected tuberculosis . EMERGE ncy ID NET also was developed to be a mechanism for rapidly responding to new diseases or epidemics . Future plans include study of antimicrobial use, meningitis, and encephalitis, and consideration of other public health concerns such as injury and national and international network expansion. Int J Antimicrob Agents, 1998 Aug, 10(3), 191 - 205 Ventilator-associated pneumonia; Visnegarwala F et al.; Mechanically ventilated patients are at a substantially higher risk for developing nosocomial pneumonia . Overall, there is a relatively constant 1&!TN!150;3% risk per day of developing pneumonia while receiving mechanical ventilation . The sensitivity and specificity of clinical criteria alone for diagnosis of ventilator-associated pneumonias (VAP) is low . Several techniques have been developed to sample and quantitate the lower respiratory tract to improve the diagnostic yield . Gram-negative bacillary pneumonias account for the majority of the VAP . Strategies for prevention of VAP such as use of sucralfate for stress ulcer prophylaxis and selective decontamination of the digestive tract have been the focus of many clinical studies . Cost-effective preventive measures are needed to combat the increasing antimicrobial resistance, growing population of immunocompromised patients and increasing number of mechanically ventilated patients. Eur J Clin Microbiol Infect Dis, 1998 Sep, 17(9), 615 - 21 Clinical and radiological features of pulmonary disease caused by rapidly growing mycobacteria in cancer patients; Jacobson K et al.; The role of rapidly growing mycobacteria in the pathogenesis of pulmonary disease is being increasingly recognized; however, the clinical significance of these mycobacteria in patients with underlying malignancy has not been well studied . Over a 6-year period, 37 cancer patients with rapidly growing mycobacteria isolated from respiratory specimens were identified at our center . Mycobacterium chelonae group was isolated in 24 cases and Mycobacterium fortuitum in 13 cases . Of the 24 cases with cultures yielding Mycobacterium chelonae group, eight met the study criteria for infection and were determined to be clinically significant, whereas only one of the Mycobacterium fortuitum isolates was determined to represent infection . An average of two antimicrobial agents were used for treatment, most commonly clarithromycin, ciprofloxacin, and trimethoprim/sulfamethoxazole . Although the isolation of rapidly growing mycobacteria represents colonization in most cases, these bacteria, especially the Mycobacterium chelonae group, may cause pulmonary disease in cancer patients . The clinical and radiological findings are usually non-specific in this population, and patients with respiratory cultures yielding rapidly growing mycobacteria should be assessed carefully to distinguish infection from colonization . Effective therapy can be provided with oral regimens that include at least two antibiotics to which the organism is susceptible. Gene, 1998 Nov 19, 222(2), 297 - 304 Sequence and expression of Drosophila Antigen 5-related 2, a new member of the CAP gene family; Megraw T et al.; A cDNA synthesized and cloned from Drosophila melanogaster mRNA was shown to encode a protein with significant identity to the protein encoded by the Drosophila Antigen 5-related (Agr) gene . Because of its similarity to Agr, this novel cDNA was termed Antigen 5-related 2 (Agr2) . The proteins encoded by Agr and Agr2 both belong to the CAP family of proteins, which include the mammalian Cysteine-rich secretory proteins, wasp venom Antigen 5 proteins, and plant group 1 Pathogenesis-related proteins . CAP family proteins share a common core sequence, and most appear to function extracellularly . Agr2 encodes a protein that is 254 amino acids in length . The cDNA contains a short 5' untranslated region (UTR) 36bp in length, and a 3' UTR of 46bp . The protein encoded by Agr2 has 48% identity and 61% similarity to that encoded by Agr . The Agr2 gene was localized to region 12F of the X chromosome and probably lies near the Agr gene . Agr2 RNA was approx . 950nt in length and was most abundant during the larval period, although transcripts could also be detected at other developmental stages . Transcription of Agr2 is initiated in the embryo within the midgut epithelium near the site where the third midgut constriction will form . As embryogenesis proceeds, Agr2 expression expands to form a domain located just posterior to the third midgut constriction . This domain corresponds to a single loop of the midgut in late-stage embryos . Based on its expression pattern and its similarity to other CAP family proteins, the Agr2 protein is hypothesized to function either as a novel type of protease inhibitor or as an antimicrobial protein. J Nephrol, 1998 Sep-Oct, 11(5), 261 - 5 Sepsis-induced acute renal failure: unusual clinical presentation; Feriozzi S et al.; We report 4 cases of sepsis-induced acute renal failure (ARF) with peculiar clinical presentation in which the renal biopsy was the only clue to a correct diagnosis . We observed 66 cases of ARF in a 4-year experience . Seven (11%) were associated with sepsis; in 3 of these (4.5%) a shock was present . Clinical picture of the remaining 4 cases (6%) was characterized by ARF with oligoanuria and proteinuria (> 2 g/L), fever, resistant to antimicrobial therapy, negative hemocultures and severe systemic symptoms . Such a presentation could suggest a non-infectious systemic disease; renal biopsies were carried out . Histological findings consisted of microabscesses of variable size in the interstitium and within the tubular lumina . A full-dose, broad-spectrum, i.v . antimicrobial therapy was started, with favourable outcome and recovery of renal function . Our clinical experience points out that the clinical picture of ARF in course of sepsis may be variable and that its relationship with septicaemia could not be readily discernible. Am J Med, 1998 Nov, 105(5), 424 - 30 Helicobacter pylori: rational management options; Peura D; In the treatment of Helicobacter pylori-associated peptic ulcer disease, the complexity (ie, frequency and duration) of drug administration, the presence or development of bacterial antibiotic resistance, and the occurrence of side effects influence patient compliance and eradication rates, which consequently affect the costs of treatment regimens . The National Institutes of Health Consensus Conference and 1997 Digestive Health Initiative Update Conference have recommended that all patients with gastric or duodenal ulcer and H . pylori infection, whether on first presentation or recurrence, be treated with antimicrobials . However, H . pylori resistance to antimicrobials, specifically to nitroimidazole compounds, has resulted in varied and decreasing success rates of treatment regimens . Comparing the efficacy, safety, and costs of current treatment strategies for the eradication of H . pylori, a combination triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is recommended as an effective alternative to standard bismuth-based triple therapy . When compared with other therapies, these offer more rapid symptomatic relief, improved tolerability, increased compliance and efficacy, and moderate costs. Liver, 1998 Oct, 18(5), 320 - 5 Fungal colonisation and fluconazole therapy in acute liver disease; Fisher NC et al.; BACKGROUND/AIMS: Fungal infection, particularly with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure . Fungal colonisation of superficial mucosal sites usually precedes invasive infection . We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole-resistant C . albicans or other species . METHODS: During a 6-month study period, we studied all patients referred to our unit with acute liver disease by twice-weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate . Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol . RESULTS: Twenty-two patients with acute liver disease were studied, eight of whom underwent transplantation . Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy . Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death . There were no other invasive fungal infections identified during the study period, and no fluconazole-resistant C . albicans were identified . CONCLUSIONS: Resistance to fluconazole is unlikely to develop in C . albicans during short-term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp . during fluconazole therapy . However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp. J Hosp Infect, 1998 Nov, 40(3), 193 - 201 Prevention of central venous catheter-related infection; Elliott TS et al.; Infections associated with central venous catheters continue to be a major source of sepsis, particularly in hospitalized patients . In developing a strategy for the prevention of these infections, the source and route of invasion of the causative micro-organisms need to be considered . The main source of micro-organisms is the patient's skin . They can gain access to a catheter at the time of insertion, as well as via the external or internal catheter surfaces . Attempts to reduce the incidence of infections range from the type of skin preparation selected, to care of the insertion site post-catheterization . Improvements in catheter design have also reduced the likelihood of infection and include the development of non-leachable smooth catheters with anti-adhesive coatings . More recently, catheters containing antimicrobial agents have become available and preliminary studies have demonstrated a reduction in microbial colonization and associated sepsis . Future preventative strategies may include the application of low voltage electric current in combination with antimicrobials. Aust Vet J, 1998 Oct, 76(10), 664 - 6 Surgical management of an abdominal abscess in a Malayan tapir; Lambeth RR et al.; A captive Malayan tapir was observed to have inappetence, weight loss, signs of depression, mild dehydration and diarrhoea . Haematological and serum biochemical tests showed anaemia, hypoproteinaemia, hyperfibrinogenaemia and neutrophilia with a left shift . Ultrasonic examination of the abdomen under anaesthesia revealed a well-encapsulated abscess . The abscess was marsupialised to the ventral body wall . Culture of the pus produced a mixed bacterial growth . Antimicrobial therapy was based on bacterial sensitivity results . Follow-up ultrasonic examinations showed resolution of the abscess . Ninety-one days after surgery the tapir began regurgitating food and water . An abscess originating from the stomach and occluding the lumen of the duodenum was identified at surgery . The abscess ruptured during surgical manipulations and the tapir was euthanased. Strahlenther Onkol, 1998 Nov, 174 Suppl 3, 90 - 2 Management of radiation injuries of vulva and vagina; Fraunholz IB et al.; BACKGROUND: Acute and late injuries of vulva and vagina are frequent and potentially serious complications in radiotherapy of gynecologic tumors . They still are reported poorly in literature . METHODS: Based on a literature search a survey will be given of the modalities, which are used or recommended for prophylaxis or treatment of these radiation injuries . The principles of the different measures will be discussed with available study results . RESULTS: Hygiene measures and the topical application of antimicrobial or granulation stimulating substances, which is mostly based on long standing clinical experience, are the principles of the treatment of acute reactions of vulva and vagina . The topical use of estrogen, which promotes proliferation of epithelium, is generally described in connection with treatment and prophylaxis of late radiation injuries . As a prophylaxis for the late reaction of vaginal stenosis, vaginal dilatation is recommended in literature . CONCLUSIONS: With the exception of a few reports on estrogen, there are no data about the effectiveness of the currently used medical substances . The local application of estrogen as prophylaxis of the acute reactions will therefore be examined in a prospective study. Strahlenther Onkol, 1998 Nov, 174 Suppl 3, 66 - 8 The treatment of late radiation effects with hyperbaric oxygenation (HBO); Plafki C et al.; BACKGROUND: Late radiation injuries may impose a negative influence on the quality of life in the affected patients . In several entities, standardized treatment protocols are lacking . Hyperbaric oxygenation (HBO) has been shown to have beneficial effects in the treatment of late radiation sequelae . MATERIAL AND METHODS: The basic principles of HBO are reviewed as well as clinical issues . Current study protocols are presented . RESULTS: During HBO-therapy the patient breathes pure oxygen at pressures above 100 kPa . The oxygen solubility within the fluid phase of the blood is largely increased . Biological effects include an increased oxygen diffusibility, improved collagen synthesis and neoangiogenesis as well as an enhancement of antimicrobial defenses . By decreasing the capillary filtration pressure a reduction of edema becomes possible . HBO has been shown to prevent complications following surgery in irradiated tissues . Its efficacy as an adjunct in the treatment of osteonecroses in radiation patients could be demonstrated . In addition, the loss of osseointegrated implants in the maxillofacial bones of these patients could be significantly reduced . Further indications include soft tissue necroses, hemorrhagic cystitis and proctitis in tumor patients that have been treated by radiotherapy as part of a multimodality approach . CONCLUSIONS: HBO in the treatment of late radiation effects is still subject of investigation, but remarkable results have been reported . Optimized treatment protocols need to be determined in various entities . The rate of side effects is acceptable low. J Indian Med Assoc, 1998 Jul, 96(7), 202 - 4 Comparative evaluation of antimicrobial activity of polyvinylpyrrolidone (PVP)-iodine versus topical antibiotics in cataract surgery; Chaudhary U et al.; Comparative evaluation of polyvinylpyrrolidone (PVP)-iodine versus topical broad-spectrum antibiotics for disinfecting the eye and surrounding area to prevent postoperative complications was carried out on 100 patients . PVP-iodine proved superior antiseptic for pre-operative preparation of eyes before cataract surgery . It was cheaper, caused minimal side-effects, reduced bacterial counts to a great extent and eliminated fungi completely. J Clin Pathol, 1998 Aug, 51(8), 568 - 75 A review of immunofluorescent patterns associated with antineutrophil cytoplasmic antibodies (ANCA) and their differentiation from other antibodies; Savige JA et al.; AIM: To describe the neutrophil fluorescent patterns produced by antineutrophil cytoplasmic antibodies (ANCA) with different antigen specificities, and by other auto- and alloantibodies . BACKGROUND: Most sera from patients with active generalised Wegener's granulomatosis result in diffusely granular cytoplasmic neutrophil fluorescence with internuclear accentuation (cANCA) and proteinase 3 (PR3) specificity . About 80% of the sera from patients with microscopic polyangiitis result in perinuclear neutrophil fluorescence with nuclear extension (pANCA) and myeloperoxidase (MPO) specificity, or a cANCA pattern with PR3 specificity . However, many different neutrophil fluorescence patterns are noted on testing for ANCA in routine immunodiagnostic laboratories . METHODS: Sera sent for ANCA testing, or containing a variety of auto- and alloantibodies, were studied . They were examined by indirect immunofluorescence according to the recommendations of the first international ANCA workshop, and for PR3 and MPO specificity in commercial and in-house enzyme linked immunosorbent assays (ELISA) . RESULTS: Sera with typical cANCA accounted for only half of all neutrophil cytoplasmic fluorescence . Other sera had "flatter" fluorescence without internuclear accentuation, and the corresponding antigens included MPO and bactericidal/permeability increasing protein (BPI), but were usually unknown . Peripheral nuclear fluorescence without nuclear extension occurred typically when the antigens were BPI, lactoferrin, lysozyme, elastase, or cathepsin G . Most types of ANA were evident on ethanol fixed neutrophil nuclei . AntidsDNA, antiRo, and antilamin antibodies resembled pANCA . Antimicrobial and antiribosomal antibodies produced cytoplasmic fluorescence, and antiGolgi antibodies, a pANCA . Sera from patients with anti-smooth muscle antibodies were associated with cytoplasmic fluorescence . There was no neutrophil fluorescence with anti-skeletal muscle and anti-heart muscle antibodies, anti-liver/kidney microsomal, antithyroid microsomal, or antiadrenal antibodies . Alloantibodies such as antiNB1 typically resulted in cytoplasmic fluorescence of only a subpopulation of the neutrophils . CONCLUSIONS: The ability to distinguish between different neutrophil fluorescence patterns, and the patterns seen with other auto- and alloantibodies is helpful diagnostically . However, the demonstration of MPO or PR3 specificity by ELISA will indicate that the neutrophil fluorescence is probably clinically significant, and that the diagnosis is likely to be Wegener's granulomatosis or microscopic polyangiitis. Br J Ophthalmol, 1998 Aug, 82(8), 919 - 25 Randomised trial of 0.2% chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in Bangladesh; Rahman MR et al.; AIM: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries . The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis . METHODS: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy . They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5% . The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals . The outcome measures were healing at 21 days and presence or absence of toxicity . If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial . RESULTS: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin . One allocated to natamycin grew bacteria and therefore was excluded from the analysis . None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days . Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04) . If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers . Equal numbers of Aspergillus (22) and Fusarium (22) were grown . The Aspergillus were the most resistant to either primary treatment . CONCLUSIONS: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available. Exp Cell Res, 1998 Nov 25, 245(1), 214 - 20 Induction of lactoferrin expression in murine ES cells by retinoic acid and estrogen; Geng K et al.; Lactoferrin is an iron-binding glycoprotein present in high concentrations in milk and exocrine fluids such as bile and tears . Many functions have been attributed to lactoferrin, including antimicrobial and antiviral activities, immunomodulation, and cell growth regulation . Lactoferrin expression is controlled by different regulators, including retinoic acid and estrogen . However, the expression pattern of lactoferrin in mammalian early development has not yet been reported . Murine embryonic stem cells are pluripotent cells that can contribute to all tissues and were used for this study . We show here that while no lactoferrin protein or mRNA was detected in untreated murine embryonic stem cells, retinoic acid and estrogen can induce high levels lactoferrin expression in these cells . Expression, demonstrated by reverse transcription-polymerase chain reaction, Western blot, immunofluorescence, and ELISA assay, was dose and time dependent . Our study provides an in vitro model for examining lactoferrin expression in early development and differentiation . Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 1998 Jul, 120(1), 121 - 6 Antimicrobial activity of the diterpenes flexibilide and sinulariolide derived from Sinularia flexibilis Quoy and Gaimard 1833 (Coelenterata: Alcyonacea, Octocorallia); Aceret TL et al.; The soft coral Sinularia flexibilis is rarely overgrown by bacteria and algae . Various studies have shown that it contains diterpenes that protect it from competitors and predators . However, of the many diterpenoids isolated from S . flexibilis, only sinulariolide has been studied for antibiotic properties . Samples of soft corals were collected from Orpheus Island and freeze-dried for chemical extraction and isolation of pure diterpenes . Antimicrobial activity of the diterpenes was determined using the disc assay method with antibiotics as controls and the minimum inhibitory concentrations of the diterpenes were determined using the Tube Dilution Technique . Two out of the five diterpenes tested (sinulariolide and flexibilide), showed marked antimicrobial activity and inhibited growth of Gram-positive bacteria . Flexibilide was effective even at concentrations as low as 5 ppm, whereas sinulariolide was effective at concentrations of 10 ppm . These compounds show potential as antibiotics. Proc Natl Acad Sci U S A, 1998 Nov 24, 95(24), 14337 - 42 Analysis of the Drosophila host defense in domino mutant larvae, which are devoid of hemocytes; Braun A et al.; We have analyzed the Drosophila immune response in domino mutant larvae, which are devoid of blood cells . The domino mutants have a good larval viability, but they die as prepupae . We show that, on immune challenge, induction of the genes encoding antimicrobial peptides in the fat body is not affected significantly in the mutant larvae, indicating that hemocytes are not essential in this process . The hemocoele of domino larvae contains numerous live microorganisms, the presence of which induces a weak antimicrobial response in the fat body . A full response is observed only after septic injury . We propose that the fat body cells are activated both by the presence of microorganisms and by injury and that injury potentiates the effect of microorganisms . Survival experiments after an immune challenge showed that domino mutants devoid of blood cells maintain a wild-type resistance to septic injury . This resistance was also observed in mutant larvae in which the synthesis of antibacterial peptides is impaired (immune deficiency larvae) and in mutants that are deficient for humoral melanization (Black cells larvae) . However, if domino was combined with either the immune deficiency or the Black cell mutation, the resistance to septic injury was reduced severely . These results establish the relevance of the three immune reactions: phagocytosis, synthesis of antibacterial peptides, and melanization . By working in synergy, they provide Drosophila a highly effective defense against injury and/or infection. Proc Natl Acad Sci U S A, 1998 Nov 24, 95(24), 14100 - 5 Nitrosative stress: metabolic pathway involving the flavohemoglobin; Hausladen A et al.; Nitric oxide (NO) biology has focused on the tightly regulated enzymatic mechanism that transforms L-arginine into a family of molecules, which serve both signaling and defense functions . However, very little is known of the pathways that metabolize these molecules or turn off the signals . The paradigm is well exemplified in bacteria where S-nitrosothiols (SNO)-compounds identified with antimicrobial activities of NO synthase-elicit responses that mediate bacterial resistance by unknown mechanisms . Here we show that Escherichia coli possess both constitutive and inducible elements for SNO metabolism . Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed flavohemoglobin of poorly understood function, is central to the inducible response . Remarkably, the protein has evolved a novel heme-detoxification mechanism for NO . Specifically, the heme serves a dioxygenase function that produces mainly nitrate . These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reactions that were thought to occur only by chemical means . Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolutionary conserved, but have been adapted for cell-specific function. Infect Immun, 1998 Dec, 66(12), 5948 - 54 Detection of anionic antimicrobial peptides in ovine bronchoalveolar lavage fluid and respiratory epithelium; Brogden KA et al.; Three small antimicrobial anionic peptides (AP) were originally isolated from an ovine pulmonary surfactant . However, their presence in bronchoalveolar lavage (BAL) fluid and tissues of the respiratory tract is unknown . In this study, we made affinity-purified rabbit polyclonal and mouse monoclonal antibodies to synthetic H-DDDDDDD-OH . Antibody specificity was assessed by a competitive enzyme-linked immunosorbent assay (ELISA), and the exact epitope binding sites were determined with analog peptides synthesized on derivatized cellulose . These antibodies were used to detect AP in BAL fluid by ELISA and in respiratory tissues by Western blot analysis and immunocytochemistry . BAL fluid from 25 sheep contained 0.83 +/- 0.33 mM AP (mean +/- standard deviation; range, 0.10 to 1.59 mM) and was antimicrobial . The presence of AP in BAL fluid was confirmed by reverse-phase high-pressure liquid chromatography fractionation followed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry on those fractions which were positive by competitive ELISA and demonstrated antimicrobial activity . In Western blots, polyclonal antibody PAB96-1 and monoclonal antibody 1G9-1C2 (5.0 micrograms/ml) detected four bands in solubilized turbinate and tracheal epithelial cells (53.7, 31.2, 28.0, and 25.7 kDa) and five bands in lung homogenates (53.5, 37.1, 31.2, 28.0, and 25.7 kDa) . Only a single band was seen in solubilized liver and small-intestine homogenates, and no bands were seen in blots containing BAL fluid, albumin, or kidney or spleen homogenates . In pulmonary-tissue sections, both antibodies PAB96-1 and 1G9-1C2 identified accumulated protein in the apical cytoplasm of the bronchial and bronchiolar epithelia, in the cytoplasm of pulmonary endothelial cells, and in an occasional alveolar macrophage . As a first step in identifying a candidate AP precursor gene(s), degenerate oligonucleotides representing all possible coding combinations for H-GADDDDD-OH and H-DDDDDDD-OH were synthesized and used to probe Southern blots of sheep genomic DNA . Following low-stringency washes and a 2-day exposure, strongly hybridizing bands could be identified . One degenerate oligonucleotide, SH87, was used as a hybridization probe to screen a sheep phage genomic library . Two independent phage contained the H-GADDDDD-OH coding sequence as part of a larger predicted protein . AP may originate as part of an intracellular precursor protein, with multistep processing leading to the release of the heptapeptide into mucosal secretions . There it may interact with other innate pulmonary defenses to prevent microbial infection. Infect Immun, 1998 Dec, 66(12), 5607 - 12 The lipopolysaccharide of Bordetella bronchiseptica acts as a protective shield against antimicrobial peptides; Banemann A et al.; Resistance profiles of the two Bordetella species B . bronchiseptica and B . pertussis against various antimicrobial peptides were determined in liquid survival and agar diffusion assays . B . bronchiseptica exhibited significantly higher resistance against all tested peptides than B . pertussis . The most powerful agents acting on B . bronchiseptica were, in the order of their killing efficiencies, cecropin P > cecropin B > magainin-II-amide > protamine > melittin . Interestingly, for B . bronchiseptica, the resistance level was significantly affected by phase variation, as a bvgS deletion derivative showed an increased sensitivity to these peptides . Tn5-induced protamine-sensitive B . bronchiseptica mutants, which were found to be very susceptible to most of the cationic peptides, were isolated . In two of these mutants, the genetic loci inactivated by transposon insertion were identified as containing genes highly homologous to the wlbA and wlbL genes of B . pertussis that are involved in the biosynthesis of lipopolysaccharide (LPS) . In agreement with this finding, the two peptide-sensitive mutants revealed structural changes in the LPS, resulting in the loss of the O-specific side chains and the prevalence of the LPS core structure . This demonstrates that LPS plays a major role in the resistance of B . bronchiseptica against the action of antimicrobial peptides and suggests that B . pertussis is much more susceptible to these peptides due to the lack of the highly charged O-specific sugar side chains. Khirurgiia (Mosk), 1998, (10), 54 - 7 {Treatment of pyogenic complications after reconstructive surgery on blood vessels with use of synthetic prosthesis}; Mikhailov IP et al.; Factors influencing result of surgical treatment of patients with festered postoperative wounds have been studied . Algorythm of determination of tactics for examination and treatment of this category of patients was established . The results obtained are based on the analysis of personal surgical treatment autcomes in 1526 patients with decompensated ischemia of extremities and 57 patients with clinical symptoms of deep suppuration . Division of purulent complications into primary and secondary is suggested . Effectiveness of various modes of prophylaxis was studied--systemic and indirect endolymphatic route for introduction antibiotics, intraoperative application of pellicle ESBA, usage of antimicrobial vascular prosthesis "SISAN" . The best results were obtained in the two latter methods . Various methods of surgical treatment in infected vascular prosthesis are reviewed. Crit Rev Oral Biol Med, 1998, 9(4), 399 - 414 Epithelial antimicrobial peptides: review and significance for oral applications; Weinberg A et al.; Epithelial tissues provide the first line of defense between an organism and the environment . Disruption of this barrier leads to bacterial invasion and subsequent inflammation . This is precisely the situation existing in the human oral cavity, where tissues are constantly exposed to a variety of microbial challenges that can lead to bacterially induced periodontal diseases, and to infections of the oral mucosa by bacteria, fungi, and viruses . With the recent discoveries of host-derived peptide antibiotics in mammalian mucosal epithelium, a new line of investigation is emerging to test the hypothesis that one class of these peptides, called "beta-defensins", functions to protect the host against microbial pathogenesis at these critical, confrontational sites . In that light, impairment of beta-defensin activity has recently been implicated in chronic bacterial infections in cystic fibrosis patients . The first direct evidence of expression of defensin peptides in the oral mucosa was the identification of a novel epithelial beta-defensin in mammalian tongue . It was shown to be upregulated in inflammation, suggesting that it participates in host defense . It is theorized that epithelial cell-derived antimicrobial peptides function to keep the natural flora of micro-organisms in a steady state in different niches such as the skin, the intestines, the airway, the endocervix, and the mouth . There is now evidence indicating that normal gingival epithelial cells and tissues express two beta-defensins, hBD-1 and the newly described hBD-2 . In addition, a cathelin-class antimicrobial peptide, designated LL-37 and found in human neutrophils, is also expressed in skin and gingiva . It is highly likely that these and/or other epithelial antimicrobial peptides play an important role in determining the outcome of the host-pathogen interaction at the oral mucosal barrier, and that they may have important future applications in antibiotic treatment. Clin Pediatr (Phila), 1998 Nov, 37(11), 665 - 71 Current attitudes regarding use of antimicrobial agents: results from physician's and parents' focus group discussions; Barden LS et al.; Antibiotics are widely prescribed for children with nonspecific upper respiratory tract infections, contributing to the recent emergence of resistant pneumococci . To understand the reasons for the overprescription of antibiotics, we conducted focus groups with parents and with pediatricians and family physicians to assess their attitudes regarding the use of antibiotics . Physicians asserted that their own antibiotic prescribing could be safely reduced . Parental expectation to receive antibiotics was a major factor influencing their overuse of antibiotics . Parents indicated that they would be satisfied with the medical visit even if antibiotics were not prescribed, provided the physician explained the reasons for the decision . This study highlights differences in physician and parent perceptions about antibiotic overuse and suggests that educational efforts to narrow this communication gap will be important for improving antibiotic use. Arzneimittelforschung, 1998 Oct, 48(10), 1019 - 23 Synthesis, antifungal activity and antibacterial evaluation of some 3-piperazinylmethyl-5-aryl-1H-1,2,4-triazoles; Papakonstantinou-Garoufalias SS et al.; Some new 3-piperazinylmethyl-5-aryl-1H-1,2,4-triazoles have been prepared and tested for their antifungal and antimicrobial activity . Among them, compounds 3g and 3h exhibited higher antifungal activity than ketoconazole against Cladosporium cladosporoides and Aspergillus niger respectively. Ann Pharmacother, 1998 Nov, 32(11), 1234 - 8 Information contents of drug advertisements: an Indian experience; Lal A; OBJECTIVE: To critically analyze the drug information contained in Indian pharmaceutical advertisements . DESIGN: Analysis of pharmaceutical advertisements supplied by drug representatives (DRs) to prescribers from July 1, 1995, to June 30, 1996 . SETTING: A university-affiliated urban teaching hospital in India . PARTICIPANTS: 585 pharmaceutical ad pamphlets . MAIN OUTCOME MEASURES: The ads supplied by DRs to physicians in different clinical departments of the hospital were collected . These were distributed to different systems/categories and a special reference to fixed-dose drug combinations was given . The drug information contained in these ads was evaluated by using a checklist, framed by incorporating the World Health Organization ethical guidelines for medicinal drug promotion and some relevant items from other studies . RESULTS: The most frequently occurring ads were for antimicrobial agents . The ads on fixed-dose drug combinations constituted 37.9% of the total . More than 85% of the ads mentioned the generic name, brand name, contents, and pharmaceutical dosage forms, as well as the name and address of the company . The information concerning adverse effects, precautions, contraindications, warnings, major interactions, ingredients known to cause problems, pharmacology, drug overdose, references, drug storage, and cost was present in less than 40% of these ads . CONCLUSIONS: There has been inadequate information in pharmaceutical ads supplied by DRs to the physicians in India . The current scenario could be improved by formulating some definite legislative guidelines for the minimum level of information to be included in pharmaceutical ads and adhering to that legislation. J Clin Pharmacol, 1998 Nov, 38(11), 1063 - 71 Pharmacodynamic interactions of ciprofloxacin, piperacillin, and piperacillin/tazobactam in healthy volunteers; Strenkoski-Nix LC et al.; Mathematical modeling methods were used to study pharmacokinetic and pharmacodynamic interactions of the antimicrobial combinations piperacillin plus ciprofloxacin and piperacillin plus tazobactam . Twelve healthy volunteers received the following treatments: piperacillin (4 g), ciprofloxacin (400 mg), piperacillin (4 g) plus ciprofloxacin (400 mg), and piperacillin (4 g) plus tazobactam (0.5 g), via intravenous infusion in a four-period crossover design . Serum drug concentrations were analyzed by means of high-performance liquid chromatography (HPLC), and inhibitory titers were performed against eight organisms . The pharmacodynamic response (growth or no growth) was modeled for each of the monotherapy courses using a Hill-type model where Emax was 1 (100% probability of no growth {P(NG)}), and EC50 was the concentration associated with a 50% P(NG) . For piperacillin plus ciprofloxacin, P(NG) was a function of 1) plasma concentrations for both drugs; 2) EC50 values from the monotherapy courses; and 3) theta, an interaction term that accommodates synergy, additivity, or antagonism . For piperacillin/tazobactam, the serum ultrafiltrate area under the inhibitory curve was compared with that of piperacillin alone to determine the benefit of tazobactam . The interaction between piperacillin and ciprofloxacin was additive . The addition of tazobactam to piperacillin was beneficial against certain organisms . The model developed can be used to evaluate the activity of combination regimens against representative pathogens. FEBS Lett, 1998 Oct 23, 437(3), 258 - 62 Parasin I, an antimicrobial peptide derived from histone H2A in the catfish, Parasilurus asotus; Park IY et al.; In response to epidermal injury, Parasilurus asotus, a catfish, secreted a strong antimicrobial peptide into the epithelial mucosal layer . The molecular mass of the antimicrobial peptide, named parasin I, was 2000.4 Da, as determined by matrix-associated laser desorption ionization mass spectrometry . The complete amino acid sequence of parasin I, which was determined by automated Edman degradation, was Lys-Gly-Arg-Gly-Lys-Gln-Gly-Gly-Lys-Val-Arg-Ala-Lys-Ala-Lys-Thr-Arg-Ser- Ser . Eighteen of the 19 residues in parasin I were identical to the N-terminal of buforin I, a 39-residue antimicrobial peptide derived from the N-terminal of toad histone H2A {Kim et al . (1996) Biochem . Biophys . Res . Commun . 229, 381-387}, which implies that parasin I was cleaved off from the N-terminal of catfish histone H2A . Parasin I showed strong antimicrobial activity, about 12-100 times more potent than magainin 2, against a wide spectrum of microorganisms, without any hemolytic activity . Circular dichroism spectra of parasin I indicated a structural content of 11% alpha-helix, 33% beta-sheet, and 56% random coils . The beta-sheet axial projection diagram of parasin I showed an amphipathic structure . Our results indicate that the catfish may produce parasin I from its histone H2A by a specific protease upon injury to protect against invasion by microorganisms. J Chromatogr B Biomed Sci Appl, 1998 Sep 25, 716(1-2), 325 - 34 Capillary electrophoresis with laser-induced fluorescence: a routine method to determine moxifloxacin in human body fluids in very small sample volumes; Moller JG et al.; The feasibility of capillary electrophoresis with HeCd laser-induced fluorescence detection as a validated routine method for bioanalytical analysis is reported . Method evaluation, validation and results of the determination of moxifloxacin (BAY 12-8039), a new antimicrobially active 8-methoxy-quinolone, in plasma and microdialysate are described . After a one step sample preparation the samples can be injected directly into the capillary . The volume of microdialysate and plasma, respectively, needed for more than 50 injections is only 10 microl and 20 microl . Total run time is less than 7 min using a 27 cm capillary on commercial instrumentation . An analysis time of less than 1 min was shown to be possible, however it could not be used routinely since appropriate instrumentation was not available . Evaluation is based on the relative corrected peak area (analyte/I.S.) . The method's dynamic range comprises three orders of magnitude (plasma: 2.5-5000 microg/l; microdialysate: 5-5000 microg/l) . Validation according to international guidelines yielded data on accuracy and precision of the method throughout the entire working range of inter-day precision: plasma <6%, microdialysate <5% and inter-day accuracy: plasma <2%, microdialysate <4% . The crossvalidation with an existing HPLC method utilizing clinical study samples shows linear correlation . In view of its adequate sensitivity and high selectivity capillary electrophoresis with laser-induced fluorescence is a very versatile tool in pharmacokinetic studies of quinolones, especially in situations with limited sample volumes: e . g . pediatrics, patients at risk, animal-, microdialysis- and tissue-kinetic studies . Validation parameters and other features, like high sample throughput and robustness, are comparable to or even better than HPLC . Further necessary improvements of the capillary electrophoresis with laser-induced fluorescence instrumentation (autosampler, vials, parallel capillaries) and its use in bioanalytical routine analysis are discussed. Chest, 1998 Nov, 114(5), 1264 - 8 Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction; O'Donnell WJ et al.; STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP . DESIGN: Prospective cohort evaluation . SETTING: University medical center . PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP . MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year . RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis . A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34) . Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse . CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP . Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis . A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk. J Leukoc Biol, 1998 Nov, 64(5), 595 - 9 Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide; Mitsuhashi H et al.; Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways . Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin . A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response . We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils . Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense . A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats . Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs. Diagn Microbiol Infect Dis, 1998 Oct, 32(2), 131 - 5 Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY Antimicrobial Surveillance Program (1998); DiPersio JR et al.; Fluoroquinolone resistance in Moraxella catarrhalis isolates has been quite rare . This report presents a case history of a 22-year-old man with compromised immune status and severe pneumonia caused by M . catarrhalis . The organism was markedly resistant (MICs, 1.5- > 32 micrograms/mL) to several marketed fluoroquinolones including the agent (levofloxacin) used for concurrent and prior therapy . The emergence of this problematic strain seems related to chronic exposure of the patient to compounds in the class and poor patient compliance to prescribed medications . The strain was not clonally related to other M . catarrhalis strains isolated in the same hospital during early 1998 . This second documented case of a fluoroquinolone-resistant M . catarrhalis clinical isolate presents a warning that resistances can emerge in at-risk patients, and that surveillance systems (SENTRY) will be necessary to monitor for unusual organisms and spread of resistance phenotypes among commonly isolated respiratory tract pathogens. J Biol Chem, 1998 Nov 27, 273(48), 31985 - 91 Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants; Koga J et al.; When plants interact with certain pathogens, they protect themselves by generating various chemical and physical barriers called the hypersensitive response . These barriers are induced by molecules called elicitors that are produced by pathogens . In the present study, the most active elicitors of the hypersensitive response in rice were isolated from the rice pathogenic fungus Magnaporthe grisea, and their structures were identified as cerebrosides A and C, sphingolipids that were previously isolated as inducers of cell differentiation in the fungus Schizophyllum commune . Treatment of rice leaves with cerebroside A induced the accumulation of antimicrobial compounds (phytoalexins), cell death, and increased resistance to subsequent infection by compatible pathogens . The degradation products of cerebroside A (fatty acid methyl ester, sphingoid base, and glucosyl sphingoid base) showed no elicitor activity . Hydrogenation of the 8E-double bond in the sphingoid base moiety or the 3E-double bond in the fatty acid moiety of cerebroside A did not alter the elicitor activity, whereas hydrogenation of the 4E-double bond in the sphingoid base moiety led to a 12-fold decrease in elicitor activity . Furthermore, glucocerebrosides from Gaucher's spleen consisting of (E)-4-sphingenine and cerebrosides from rice bran mainly consisting of (4E,8E)-4,8-sphingadienine and (4E,8Z)-4,8-sphingadienine showed no elicitor activity . These results indicate that the methyl group at C-9 and the 4E-double bond in the sphingoid base moiety of cerebrosides A and C are the key elements determining the elicitor activity of these compounds . This study is the first to show that sphingolipids have elicitor activity in plants. J Antibiot (Tokyo), 1998 Sep, 51(9), 857 - 71 Preparation and antimicrobial assessment of 2-thioether-linked quinolonyl-carbapenems; Hershberger PM et al.; This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems . Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones . Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase . Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump. Clin Exp Immunol, 1998 Nov, 114(2), 258 - 63 Adhesion molecules in common variable immunodeficiency (CVID)--a decrease in L-selectin-positive T lymphocytes; Nordoy I et al.; CVID is immunologically characterized by defective antibody production . Various additional immunological abnormalities have been reported, but little is known of the role of adhesion molecules in CVID . In 31 CVID patients serum levels of L-selectin (CD62L), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54) were significantly elevated compared with controls . In 15 CVID patients investigated, the number of L-selectin-positive cells was significantly reduced in both CD4+ and CD8+ lymphocytes compared with controls, and these changes were observed in both CD45RA+ and CD45RO+ subsets . In CD19+ lymphocytes the percentage of ICAM-1+ cells was significantly increased compared with controls . Fifty percent of the patients had splenomegaly . These patients demonstrated even higher serum levels of adhesion molecules, a lower percentage of L-selectin-positive and a higher percentage of CD38+ cells in many T lymphocyte subsets compared with both other CVID patients and controls . Finally, in this patient group the percentage of L-selectin-positive CD19+ lymphocytes was significantly reduced compared with both other patients and controls . These findings indicate a state of ongoing T lymphocyte activation in CVID, especially in the subgroup of patients with splenomegaly, which may contribute to the impaired antimicrobial defence observed in these patients. Toxicol Lett, 1998 Aug, 96-97, 47 - 51 Formation of nitric oxide by rat and hamster alveolar macrophages: an interstrain and interspecies comparison; Jesch NK et al.; Nitric oxide (NO) plays an important role in non-specific host defense, which can be recognized by its antimicrobial and cytotoxic activity against pathogens . However, there appear to exist interspecies differences in the ability of macrophages to generate NO . The object of this study was to determine whether there exist intraspecies differences in the production of NO . We compared NO formation by alveolar macrophages (AM) from five different rat strains (Sprague Dawley, Wistar, Lewis, Fisher, and Brown Norway), two different stocks of Syrian Golden hamsters, and one stock of Chinese hamsters . The AM were harvested by bronchoalveolar lavage and stimulated in vitro with various concentrations of LPS and/or IFN-gamma . The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction . Upon stimulation with LPS and/or IFN-gamma, AM from all five rat strains were able to release NO, but the amount of NO produced differed significantly among the rat strains . However, none of the stimuli was able to induce AM from the two stocks of Syrian Golden hamsters as well as AM from the stock of Chinese hamsters to release measurable amounts of NO . These findings point to distinct regulatory mechanisms of the NO pathway in AM from different species and to variations of this mechanism in the AM from the investigated rat strains. J Immunol, 1998 Nov 15, 161(10), 5217 - 25 CD40 engagement triggers switching to IgA1 and IgA2 in human B cells through induction of endogenous TGF-beta: evidence for TGF-beta but not IL-10-dependent direct S mu-->S alpha and sequential S mu-->S gamma, S gamma-->S alpha DNA recombination; Zan H et al.; IgA are major effectors of antimicrobial defense in the respiratory and digestive tracts . We have analyzed the requirements for and the modalities of switching to IgA using our recently identified monoclonal model of human germinal center differentiation, CL-01 B cells . CL-01 cells bear surface IgM (sIgM) and sIgD and switch to all seven downstream isotypes in response to physiologic stimuli . In these cells, CD40 engagement by CD40 ligand induces production of endogenous TGF-beta and IL-10, expression of germline Ialpha1-Calpha1 and Ialpha2-Calpha2 transcripts, mature VHDJH-Calpha1 and VHDJH-Calpha2 transcripts, and IgA secretion . These events are associated with not only direct Smu-->Salpha, but also sequential Smu-->Sgamma, Sgamma-->Salpha DNA recombination, and are ablated by neutralizing anti-TGF-beta but not IL-10 Ab, and indicating that TGF-beta, not IL-10, is a crucial mediator of the transcriptional activation and recombination of human Calpha1 and Calpha2 genes . Our findings in CL-01 cells were reproduced in freshly isolated naive sIgM+ sIgD+ B lymphocytes . Thus, engagement of CD40, in the absence of other (known) stimuli, is sufficient to effectively induce switching to IgA in human B cells . This is effected by direct and sequential DNA recombination events, which are both dependent upon endogenous TGF-beta secreted by the CD40L-induced B cells. Lijec Vjesn, 1998 Jun, 120(6), 160 - 2 {Our initial experience with video-assisted thoracoscopic surgery (VATS)}; Ilic N et al.; Diagnostic and therapeutic potentials and our first two-year experience with video-assisted thoracic surgery (VATS) are reported . From May 1995 to April 1997, at the Department of Surgery, University Hospital Split, VATS approach was planned in 55 cases (recurrent pneumothorax in 23, tension pneumothorax in 1, traumatic effusion in 5, malignant metastatic lung tumor in 1, benignant lung tumor in 11, traumatic effusion in 5, suspected mediastinal lymph nodes in 4, long lasting unconfirmed pleural effusion in 9, foreign body in 1, mediastanal cyst in 1) . Of these, 48 procedures (87.2%) were performed using VATS (diagnostic thoracoscopy in 12, wedge resection with or without pleural abrasion in 21, partial pleurectomy in 1, decortications in 3, mediastinal lymph nodes biopsy in 4, lung biopsy in 7) . Seven patients (12.7%) underwent conventional posterolateral thoracotomy . Complications included persistent air leak in three patients, prolonged bleeding in one patient and supraventricular tachycardia in one patient . The mean duration of chest tube drainage after the procedure was 3.7 days (range 2 to 19 days), and mean hospital stay was 5.1 days (range 3 to 15 days) . All patients received routine antimicrobial chemoprophylaxis with single-dose ceftriaxone 2 g intravenously immediately prior to the surgery, and average postoperative patient-controlled analgesia with buprenorphine 0.15 mg . We conclude that VATS is a very useful alternative to conventional thoracotomy in managing cases of exploration, recurrent spontaneous pneumothorax, benign pulmonary lesions, solitary pulmonary nodes, early decortications and different intrathoracic biopsies. J Infect, 1998 Jul, 37 Suppl 1, 45 - 50 Cost issues in sequential therapy; Cooke J; Pharmacoeconomics is starting to be employed in strategic therapeutic decision making . Costs associated with antimicrobials included: (i) acquisition costs; (ii) preparation, administration and consumables costs; (iii) monitoring costs; (iv) costs of unwanted drug effects; (v) costs of resistance and therapeutic failures and (vi) costs of duration of stay . Most hospitals have a Drug and Therapeutics Committee but acquisition costs are still the most important economic criterion for acceptance for use, even though medicines only consume between 3 and 5% of total revenue costs, of which antibiotics account for around 15% . In any sequential programme acquisition costs and consumables are immediately realizable . Staff time and monitoring tests are less realizable but require changes in the way budgets are handled . Microbial resistance and risk management are difficult to quantify but are increasingly becoming important in strategic decision-making . The educational needs of health care decision makers in economic need addressing and mechanisms need to be put in place to enable the putative savings reported in the pharmacoeconomic literature to be realized. J Infect, 1998 Jul, 37 Suppl 1, 37 - 44 Sequential antibiotic therapy: the right patient, the right time and the right outcome; Davey P et al.; The aim of sequential therapy should be to provide better quality of care at lower cost . In comparison with i.v . therapy, oral administration is safer, more acceptable to the patient, facilitates early discharge from hospital and reduces the cost of consumables . However, if given to the wrong patient, oral antimicrobial therapy could both increase the cost and reduce the quality of care, either because of ineffective treatment, or unnecessary prolongation of treatment . Hospitals must develop policies for sequential therapy which define standards against which clinical care can be audited . The standards will need to be revised as new data become available from local audit and from research . Further research on sequential therapy is undoubtedly required, with particular emphasis on the reliability of absorption of oral drugs by hospitalized patients. J Infect, 1998 Jul, 37 Suppl 1, 30 - 6 Sequential antimicrobial therapy: pharmacokinetic and pharmacodynamic considerations in sequential therapy; MacGowan AP et al.; The pharmacodynamic factors important in sequential therapy are largely unknown . This is because most pharmacodynamic investigations concentrate on how bacterial populations respond to first antimicrobial exposures . However, it is likely that for B lactams T>MIC and for quinolones the antimicrobial AUC/MIC ratio will be important . Factors which reduce antimicrobial absorption will impact on these parameters and require further study. J Infect, 1998 Jul, 37 Suppl 1, 18 - 23 Sequential antimicrobial therapy: comparison of the views of microbiologists and pharmacists; Smyth ET et al.; Sequential antimicrobial therapy (SAT) is arousing keen interest in microbiologists and pharmacists . In an attempt to obtain information from these groups regarding the use of SAT in hospitals, an anonymized postal survey was carried out . A SAT questionnaire was circulated to consultant medical microbiologists, clinical microbiologists, and heads of pharmacy departments within the British Isles . Four hundred and forty-seven microbiologists and pharmacists returned completed questionnaires, giving a response rate of 29% . Just over half of medical microbiologists (MM) and pharmacists (PH) indicated that SAT was used in their institution in respiratory medicine, geriatrics, surgery and, significantly, to a lesser degree in paediatrics . The most common infections treated were pneumonia, bronchitis and wound infection . However, there were significant differences between MM and PH, with MM favouring greater use of SAT in peritonitis (P=0.03), septicaemia (P<0.01), bone infection (P<0.01), pyelonephritis (UTI) (P<0.01), and PH favouring use in bronchitis (P<0.01) . The ability to take oral fluids or a recognition of no potential absorption problems were key criteria in the decision process leading to the institution of SAT by MM and PH . Significantly more MM favoured employing criteria such as temperature <38 degrees C (P<0.01), no requirement for high tissue concentrations (P=0.02) and evidence of response to i.v . antimicrobial therapy (P<0.01) than PH . The most frequently "switched" antimicrobials were metronidazole, ciprofloxacin and co-amoxiclav . There were more than five times as many MM reporting the use of clindamycin than PH (P<0.01), whereas nearly twice as many PH cited use of cefuroxime (P<0.01) . Of those hospitals not employing SAT, most MM and PH concurred that the commonest reason to institute SAT was financial, followed by convenience to patients and staff . However, more PH than MM indicated that protocols (P<0.01) and a reduction in i.v . complications (P<0.01) were important to them . In promoting SAT, MM and PH felt they had the major role . Significantly, each profession felt that the other had a lesser role to play; MM as judged by the PH (P<0.01) and PH as judged by MM (P<0.01) . When promoting SAT, both MM and PH felt that "education for clinicians" followed by regular audit was the best way to ensure implementation . However, significant differences arose with PH regarding nurse education (P<0.01), SAT posters (P=0.02), regular review of patients (P=0.04) and patient's notes SAT stickers (P<0.01) as more important to them than MM . Significantly, less MM than PH (P<0.01) insisted that either the i.v . and PO antimicrobials were identical or were from the same group or class when "switching" . This survey highlights interesting comparisons between the approaches of MM and PH towards SAT and may indicate ways in which both groups may work together to bring about change. J Infect, 1998 Jul, 37 Suppl 1, 10 - 7 Strategies to rationalize sepsis management--a review of 4 years' experience in Dundee; Nathwani D et al.; Hospitals worldwide are facing an unprecedented crisis of rising cost of antibacterials due to the increasing rapid emergence and dissemination of antibiotic-resistant organisms, improper use of antibiotics and the use of broad spectrum parenteral agents . The last 25 years has seen the introduction of many measures to improve the quality of sepsis management, and specifically antimicrobial use . The present paper reviews the development, implementation and evaluation of some of the key strategies employed within the Dundee Teaching Hospitals NHS Trust (DTHT) to enhance recognition and assessment of sepsis and to rationalize the early and often empiric antibiotic treatment of patients in hospital with infection . Particular emphasis is given to optimizing the use of expensive parenteral agents in conjunction with promotion of oral switch therapy where appropriate. J Infect, 1998 Jul, 37 Suppl 1, 3 - 9 Programs promoting timely sequential antimicrobial therapy: an American perspective; Drew RH; Interventional programs promoting the timely conversion of intravenous to oral antimicrobial therapy have been reported from several hospitals in the U.S.A . and elsewhere . Factors influencing the initiation and conduct of these programs include technological advances, changes in health care delivery or reimbursement, publication of supportive clinical data and growth of clinical pharmacy services . Successful programs employ comprehensive, multidisciplinary strategies to contain antimicrobial-related expenditures using interventions based on structured criteria . Future emphasis on cost-effective drug therapy, advances in computer-based information technology and development of care maps can have favourable influences on the growth of these programs in the U.S.A. J Infect, 1998 Jul, 37(1), 68 - 70 Anaerobiospirillum succiniciproducens septicaemia: important aspects of diagnosis and management; Goddard WW et al.; Anaerobiospirillum succiniciproducens is a rare cause of septicaemia . A 63-year-old woman with liver cirrhosis and a history of melaena developed A . succiniciprodocens septicaemia . She owned two pet dogs and a cat . Despite supportive management and antibiotic treatment supported by in vivo testing, the patient died . The characteristics identification and antimicrobial susceptibility of A . succiniciproducens are discussed and previous reported underlying disease reviewed. J Infect, 1998 Jan, 36(1), 35 - 42 Prospective randomized study to compare imipenem 1.5 grams per day vs . 3.0 grams per day in infections of granulocytopenic patients; Bohme A et al.; The objective of this presented prospective randomized study was to compare the efficacy of empirical antimicrobial monotherapy with imipenem 3 x 0.5 g per day to 3 x 1.0 g per day for treatment of infections in neutropenic patients . A total of 192/220 febrile episodes were evaluable for clinical efficacy . The overall response rate was 53/93 (57%) vs . 57/99 (58%) . Of the different infection types, fever of unknown origin (FUO) showed the best response, with defervescence in 29/41 (71%) and 36/42 (86%) cases, respectively (not significant) . Unfavourable results were found in pneumonias {5/20 (25%) vs . 4/23 (17%)} . The median time until persistent defervescence was equal in both groups (2 days), likewise the median duration of imipenem therapy in responders (7 days) . The most frequent micro-organisms were Gram-negative, documented in 22% of the febrile episodes in the lower dosage group vs . 17% of all episodes in the patients with imipenem 3.0 g per day (Gram-positives 17% vs . 14%, fungal 5% vs . 8%) . In the lower dosage group, fever with abdominal symptoms occurred less frequently (8% vs . 15%), and significantly more patients tolerated imipenem without any side-effects (95.8% vs . 79.4%), especially regarding severe nausea/vomiting (2.1% vs . 11.8%) . Of the initial non-responders, 35/40 (88%) vs . 41/42 (98%) were cured after therapy modification . There was no significant difference in the use of further antibiotics such as aminoglycosides, glycopeptides, ceftazidime or amphotericin B, except a marginally higher use of metronidazole in patients with imipenem 3.0 g per day (3% vs . 10%) . Overall, we found no significant differences in efficacy between the two study groups, but more frequent side-effects with imipenem 3.0 g per day. Biochemistry, 1998 Nov 17, 37(46), 16033 - 40 Pore formation by nisin involves translocation of its C-terminal part across the membrane; van Kraaij C et al.; Nisin is an amphiphilic peptide with a strong antimicrobial activity against various Gram-positive bacteria . Its activity results from permeabilization of bacterial membranes, causing efflux of cytoplasmic compounds . To get information on the molecular mechanism of membrane permeabilization, a mutant of nisin Z containing the C-terminal extension Asp-(His)6 was produced . The biological and anionic lipid-dependent membrane activity of this peptide was very similar to that of nisin Z . Analysis of the pH dependence of model membrane interactions with the elongated peptide indicated the importance of electrostatic interactions of the C-terminus with the target membrane for membrane permeabilization . Most importantly, the membrane topology of the C-terminus of the molecule could be determined by trypsin digestion experiments, in which trypsin was encapsulated in the lumen of large unilamellar vesicles . The results show that the C-terminal part of the peptide translocates across model membranes . The pH and anionic lipid dependence of translocation closely paralleled the results of membrane permeabilization studies . Binding of nickel ions to the histidines blocked translocation of the C-terminus and concomitantly resulted in a 4-fold reduced capacity to induce K+ leakage . The results demonstrate for the first time that pore formation of nisin involves translocation of the C-terminal region of the molecule across the membrane. J Rheumatol, 1998 Nov, 25(11), 2249 - 53 Outcomes of children treated for Lyme disease; Wang TJ et al.; OBJECTIVE: To study the outcome of Lyme disease (LD) in children identified in a total population survey of an endemic island . METHODS: We conducted a population-based retrospective cohort study off the coast of Massachusetts . Twenty-five children who met the Centers for Disease Control case definition for prior LD were compared with 26 children without LD from the same community . All children with LD received antibiotics during the acute phase of their disease . All 51 children were invited for a clinical evaluation, including 12-lead electrocardiogram (EKG), and measurement of antibodies to Borrelia burgdorferi by antibody-capture ELISA and Western blot . RESULTS: At a mean of 3.2 years from the initial manifestation of LD, children with prior LD did not have a higher prevalence of musculoskeletal or neurological symptoms, examination abnormalities, abnormal EKG, or behavioral difficulties, compared to children with no history of LD . CONCLUSION: Children who receive appropriate antimicrobial therapy for LD appear to have no demonstrable longterm morbidity. Mayo Clin Proc, 1998 Nov, 73(11), 1114 - 22 Review of pharmacokinetics and pharmacodynamics of antimicrobial agents; Estes L; Pharmacokinetics is a science that has long been used in ascertaining the appropriate antimicrobial dose . It refers to the disposition of drugs in the body and includes absorption, bioavailability, distribution, protein binding, metabolism, and elimination . Pharmacodynamics is a newer science that relates to the interaction between the drug concentration at the site of action over time and the desired antimicrobial effect . This article reviews the principles of pharmacokinetics and pharmacodynamics as well as the clinical application of these two sciences to design antimicrobial dosing regimens for optimal results in individual patients. J Clin Microbiol, 1998 Dec, 36(12), 3713 - 7 Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation; Iwen PC et al.; The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described . The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation . She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl . Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge . Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present . The ANC at the time of readmission was 3,500 . Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus . The patient was placed on ganciclovir . A biopsy specimen from a leg lesion also noted on day 67 p.t . revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus . Confirmation detection of A . ustus was made by demonstration of characteristic reproductive structures with the presence of Hulle cells . On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated . The patient's condition worsened, and she died 79 days p.t . At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A . ustus . In vitro susceptibility testing indicated probable resistance to AMB but not to ITR . This case supports the need for the development of rapid methods to determine antifungal susceptibility. Rinsho Byori, 1998 Oct, 46(10), 978 - 86 {Consultation service for efficacious usage of laboratory tests based on logical reasoning and evidence}; Ishida H et al.; To effectively respond to the desire for consultation in clinical practice, we must prepare logical reasoning and evidence which rationally supports laboratory test selection, the interpretation of test results and recommendation of certain tests to physicians . Standard of medical decision making can be used for logic issues such as posttest probability, test characteristics and receiver operating characteristics (ROC) curves and establishing appropriate cut-off points . Although we usually obtain evidence by consulting authorities or the literature, good evidence can also be obtained from meta-analysis . In addition, we can demonstrate the relationship of laboratory tests among several frequently occurring diseases and epidemiological tendencies such as frequency of causative organisms at several infection sites and bacterial sensitivities to antimicrobial agents, because we have access to a large-scale laboratory database . To construct a well-organized knowledge base with explicit evidence, cooperation among many facilities is necessary to develop system, which allows the free exchange of data. J Travel Med, 1997 Dec 1, 4(4), 161 - 166 Prognostic Factors Related to Recovery from Diarrhea among U.S . Students with Diarrhea in Mexico; Mosavi A et al.; Background: Medical charts of subjects treated with placebo from five double-blinded placebo-controlled clinical trials were reviewed to determine pre-enrollment prognostic factors related to later recovery from diarrhea . Method: Recovery or time from initiation of a placebo until passage of the last unformed stool after being declared well was calculated for each subject . Results: A longer duration of diarrhea was associated with presence of fever (rate ratio = 0.34; 95% CI = 0.2-0.9), presence of an invasive pathogen in the stool (rate ratio = 0.35; 95% CI = 0.2-0.7) or a noninvasive pathogen in stool (rate ratio = 0.7; 95% CI = 0.6-1.0), severe abdominal pain or cramps (rate ratio = 0.5; 95% CI = 0.3-0.9), passage of more than five watery stools per 24 hours (rate ratio = 0.58; 95% CI = 0.4-0.8) . Severe vomiting predicted a shorter duration of post-enrollment diarrhea (rate ratio = 2.43; 95% CI = 1.1-5.6) . Conclusion: A number of clinical and microbiologic factors found in travelers with diarrhea in the present study predicted duration of untreated diarrhea . The authors suggest the use of antimicrobial therapy in travelers with predictors of a long duration of diarrhea . Data developed in the present study may be used to create a historical control for clinical trials of antidiarrheal compounds using the same study criteria. J Travel Med, 1997 Mar 1, 4(1), 3 - 7 Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea; Ericsson CD et al.; Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature . The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea . Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994 . Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days . The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool . Results: Ofloxacin and loperamide were well tolerated . Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001) . Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001) . Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours . Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone. Digestion, 1998 Nov-Dec, 59(6), 708 - 14 Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' diarrhea; DuPont HL et al.; BACKGROUND/AIMS: Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs . Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea . METHODS: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico . Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days . Results were compared with data from 2 placebo-treated historical control populations . RESULTS: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t . i.d (NS) . Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS) . Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS) . Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by</=50 microgram/ml of rifaximin . Rifaximin reduced the number of unformed stools passed during the first 24 h of treatment when compared with 2 control placebo groups (3.3 versus 5.1; p = 0.008 and 0.0001) and led to a reduced duration of post-enrollment diarrhea (mean values of 43.1 versus 68.1 and 81.9 h; p = 0.001) . CONCLUSIONS: Rifaximin shortened the duration of travelers' diarrhea compared with TMP/SMX and 2 earlier studied placebo-treated groups . A poorly absorbed drug if effective in treating bacterial diarrhea has pharmacologic and safety advantages over the existing drugs. Arq Gastroenterol, 1998 Apr-Jun, 35(2), 138 - 42 {Primary gastritis associated with Helicobacter pylori in children}; Kawakami E et al.; The aim of this paper was to investigate whether a correlation between dyspeptic symptoms and infection due to Helicobacter pylori could be established . We conducted a prospective study with 27 children who had Helicobacter pylori associated antral gastritis with endoscopic and histologic alterations, without any other peptic lesions . Helicobacter pylori was detected by rapid urease test and histology with hematoxylin and eosin and Giemsa stain . Endoscopy revealed antral nodularities in 20/27 (74%) and enantema in six cases (23%) . During histological examination active chronic superficial gastritis was confirmed in 26 cases (96%) . Twenty seven children were treated with antimicrobial therapy, eight of which presented infection eradication, six presented nodularities regression and symptoms remission in four . Of the 19 non-eradicated patients, eight (42%) became asymptomatic and 11 maintained symptoms . Statistical analysis to compare symptoms remission was not significant . Taking into account the results presented herewith, we concluded that antral nodularity was the most common endoscopic finding, and there was no sufficient evidence of a correlation between Helicobacter pylori infection and dyspeptic symptoms. Rev Prat, 1998 Sep 15, 48(14), 1541 - 6 {Control of multiple-resistant bacteria}; Lucet JC; The number of multiply-resistant bacteria, especially methicillin-resistant Staphyloccoccus aureus, has reached an alarming level in France . This number reflects the inadequacy of efforts against nosocomial infections, and non-respect of hygiene rules by hospital staff . Two mechanisms lead to multiple resistance: the selection of multiply-resistant bacteria by antimicrobials; and, once resistance is acquired, bacterial dissemination by hand-mediated cross transmission . Controlling the spread of multiple resistance thus requires both judicious use of antimicrobials, and compliance with basic rules of hygiene, particularly handwashing . Although the hospital setting favors the emergence and spread of bacterial resistance, this is also increasing, albeit to a lesser extent, in the non-hospital environment . The same measures of careful antimicrobial use and good hygiene should be applied. Pharmazie, 1998 Oct, 53(10), 686 - 90 Synthesis and antimicrobial activities of some new pyrrolylthieno{2,3-b}-quinoline derivatives; Geies AA et al.; 2-Acetyl-4-(p-chlorophenyl)-3-(1-pyrrolyl)-5,6,7,8- tetrahydrothieno{2,3-b}quinoline (4a) and its corresponding 2-carbohydrazide derivative 5 were prepared and used as key intermediates in the synthesis of the title compounds . Some of the synthesized compounds were screened for their antibacterial and antifungal activities. Pharmazie, 1998 Oct, 53(10), 680 - 4 Synthesis, spectral and antimicrobial properties of 5-chloroarylidene aromatic derivatives of imidazoline-4-one; Kiec-Kononowicz K et al.; The synthesis of new chloro-benzylidene substituted derivatives of hydantoin and their antimicrobial activity is reported . The structure-activity relationships showed that the antibacterial effect of investigated compounds depends on the distance of the phenyl ring from the amine residue and the kind of substitutes on the phenyl ring . In the investigated group of derivatives, 5-(2-chlorobenzylidene)-2-(4-fluorobenzylamine)-imidazoline-4-one and 5-(2-chlorobenzylidene)-2-(2-phenylethylamine)-imidazoline-4-one showed the best antibacterial activity against Moraxella catarrhalis. Infect Dis Obstet Gynecol, 1998, 6(4), 186 - 90 Chronic plasma cell endometritis in hysterectomy specimens of HIV-infected women: a retrospective analysis; Kerr-Layton JA et al.; OBJECTIVE: Abnormal uterine bleeding is a common and troublesome problem in human immunodeficiency virus (HIV)-infected women . We sought to evaluate endometrial pathology among HIV-infected women requiring hysterectomy to explore if endometritis may be common among these patients . METHODS: We performed a retrospective analysis of uterine pathology specimens obtained from HIV-infected and control patients requiring hysterectomy in two urban hospitals between 1988 and 1997 matched for age, surgical indication, and history of gonadotropin-releasing hormone (GnRH) use . Cases were evaluated for the presence of plasma cells and assigned a grade between 0 and 3 . RESULTS: Indications included cervical dysplasia (4), carcinoma in situ (2), abnormal uterine bleeding (3), and adnexal mass (3) . Some degree of abnormal uterine bleeding occurred in all cases . Plasma cell endometritis was twice as common in HIV-infected women compared to HIV-negative specimens (11/11 versus 11/22) (P < 0.05) . Plasma cell endometritis was also of a higher grade in specimens from HIV-infected women than in controls (P = 0.001) . CONCLUSION: Chronic endometritis was common and of a higher grade among HIV-infected women requiring hysterectomy in our series . Diagnosis and treatment of endometritis should be considered in HIV-infected women with uterine bleeding and/or tenderness . We speculate that antiretroviral and/or antimicrobial treatment for endometritis may effectively treat endometritis and eliminate the need for surgery in some HIV-infected women . We suggest that consideration and treatment of endometritis in HIV-1 infected women being evaluated for possible hysterectomy has the potential to reduce costs and morbidity for patients and providers who may be exposed during surgical procedures. Infect Dis Obstet Gynecol, 1998, 6(4), 155 - 9 The use of once-daily dosing of gentamicin in obstetrics and gynecology; Wiesenfeld HC et al.; Gentamicin is a widely-used antimicrobial agent for obstetric and gynecologic infections . Renewed excitement in this antibiotic has arisen from recent information supporting less frequent dosing . In this symposium, we will describe the pharmacokinetics of gentamicin and review new information advocating the use of once-daily administration of gentamicin. Coron Artery Dis, 1998, 9(6), 339 - 43 Chlamydia pneumoniae, antimicrobial therapy and coronary heart disease: a critical overview; Gupta S et al.; Traditional cardiovascular risk factors, such as smoking, hypercholesterolaemia and hypertension probably only explain about 50% of the prevalence and severity of coronary heart disease (CHD) . The recent interest in the association between Chlamydia pneumoniae and the pathogenesis and progression of atherosclerotic diseases is based on several lines of evidence-seroepidemiological studies, pathological specimen examinations, laboratory-based experiments, animal models and more recently, pilot intervention trials with anti-chlamydial antibiotics (Table 1) . Whether C . pneumoniae has a direct causal role in atherosclerosis (and its clinical sequelae), and whether antibiotics have a protective role in the secondary prevention of CHD remains unclear . The results from large scale, prospective antibiotic trials in CHD, currently in progress, should help to clarify these important issues. Zentralbl Bakteriol, 1995 Nov, 283(1), 49 - 60 In vitro antimicrobial susceptibility testing of Borrelia burgdorferi: influence of test conditions on minimal inhibitory concentration (MIC) values; Boerner J et al.; A broth microdilution assay was performed to determine the minimal inhibitory concentrations (MICs) of 25 antimicrobial agents for two strains of Borrelia (B.) burgdorferi sensu lato and one strain of B . hermsii . The method comprised BSK II medium lacking gelatin and an incubation period of 72 hours . To investigate the influence of reading mode and density of inoculum on MIC values, microscopical as well as macroscopical MIC reading was performed using standardized final inocula of 10(6) and 10(7) borreliae/ml . Data were processed by two-way analysis of variance . In the microdilution assay, MIC values were significantly influenced either by the inoculum density or reading mode . However, using clearly defined criteria for macroscopical endpoint determination, MICs from macroscopical and microscopical reading were found to be in close agreement . B . burgdorferi sensu lato strains tested were highly susceptible to azithromycin, erythromycin, mezlocillin, piperacillin as well as ceftriaxone, with MICs ranging from < or = 0.016 to 0.125 microgram/ml . B . hermsii was highly susceptible to azithromycin and erythromycin . In comparison to B . hermsii, the beta-lactam antibiotics revealed a significantly higher activity and gentamicin, ofloxacin, and rifampin revealed a significantly lower activity against B . burgdorferi sensu lato strains . To further investigate interactions between BSK II medium, incubation time, and antibiotic efficacy, an agar diffusion bioassay was performed . Out of seven antibiotics tested, the activities of mezlocillin, penicillin G, and piperacillin were significantly influenced by BSK II medium and incubation period and showed a marked decrease of on average 84.0% within 72 hours of incubation. Presse Med, 1998 Oct 10, 27(30), 1536 - 44 {Pharmacokinetics of anti-infective agents in continuous hemofiltration}; Jaumain H et al.; NEW ASSIST TECHNIQUES: Continuous hemofiltration and hemodiafiltration are two new renal replacement techniques offering continuous electrolyte regulation and hemodynamic stability in patients with multiple organ failure . These continuous techniques are being used more and more in intensive care, especially as renal replacement in case of septic shock, and probably have the additional benefit of removing toxins . EFFECT ON ANTIMICROBIALS: Little is known about the removal of drugs and in particular antimicrobials during continuous hemofiltration although both the specific pharmacokinetics of each drug and the patient's particular clinical situation plays an important role . DRUG DOSING: In the intensive care unit, knowledge of the effect of continuous hemofiltration on drug removal and pharmacokinetic profile is crucial for practical management due to the importance of avoiding infratherapeutic serum levels, or inversely toxic levels, in these seriously ill patients . Titration equations provided in most of the recent articles are helpful but usually based on a large number of parameters not always easily available in clinical practice . An approximation of the dose can be estimated from dosing guides for continuous dialysis which can be useful in avoiding poorly adapted dosage. J Interferon Cytokine Res, 1998 Oct, 18(10), 817 - 21 Bacterial extract OM85-BV induces interleukin-12-dependent IFN-gamma production by human CD4+ T cells; Byl B et al.; To obtain insight into the possible mode of action of bacterial extracts used as immunostimulants in Europe, we used the ELISPOT technique to investigate the effects of one of them (OM85-BV, Broncho-Vaxom) on interferon-y (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) . We found that (1) OM85-BV stimulates IFN-gamma secretion by PBMC from normal individuals and human immunodeficiency virus (HIV)-infected patients, (2) CD4+ cells represent the major source of IFN-gamma produced in response to OM85-BV, and (3) this effect of OM85-BV involves the induction of interleukin-12 (IL-12) secretion by accessory cells . We conclude that bacterial extracts might enhance antimicrobial defenses by eliciting IL-12-dependent IFN-gamma synthesis by CD4+ T cells. Rev Rhum Engl Ed, 1998 Oct, 65(10), 567 - 70 Rheumatic manifestations related to acrodermatitis chronica atrophicans . A review of four cases; Gerster JC et al.; BACKGROUND: Acrodermatitis chronica atrophicans is a delayed manifestation of Lyme disease caused by a Borrelia burgdorferi subspecies, B . afzelii . Although rheumatic manifestations are rare, they can result in deformities of the fingers and toes if they are not treated promptly . METHODS: We report four cases of acrodermatitis chronica atrophicans seen over a 15-year period . RESULTS: Two patients had a noninflammatory unilateral knee effusion and one had swelling of the dorsum of one hand . Antimicrobial therapy was followed by a full recovery in the three patients who received an early diagnosis . The remaining patient, a 63-year-old woman, had swelling and dysesthesia in the fingers of both hands . She developed finger deformities over a period of two years . Although the swelling resolved under antimicrobial therapy, she had persistent reducible deformities of the fingers consistent with Jaccoud's arthropathy . CONCLUSION: The diagnosis of acrodermatitis chronica atrophicans rests on a history of a tick bite, a suggestive skin biopsy histology and a positive Western blot for B . afzelii . A positive response to antimicrobial therapy is also required . Acrodermatitis chronica atrophicans, a common condition in central and northern Europe, can cause joint manifestations and persistent finger deformities in the absence of early treatment. Enferm Infecc Microbiol Clin, 1998 Aug-Sep, 16(7), 302 - 6 {Bacterial meningitis in emergency medicine . Factors associated with delay of antimicrobial therapy}; Gutierrez A et al.; BACKGROUND: Bacterial meningitis is a severe infection . Outcome might be improved if diagnosis and therapy are achieved promptly . We studied the time elapsed until antimicrobial therapy and analyzed factors associated to delay . METHODS: We performed a retrospective study of bacterial meningitis diagnosed in a hospital emergency medicine department in two consecutive years . Dependent variable was time since admission to antimicrobial therapy; delay was defined as time to administration longer than 2 h . The relationship between clinical variables and delay was studied with bivariate analysis . Significative variables were included in a multivariate analysis using multiple logistic regression . RESULTS: We studied 40 cases of bacterial meningitis (67.5% female, mean age 25.2 years) . The mean time to antibiotic therapy was 127 min; in 16 patients (40%; 95% confidence interval: 25-56%) delay was 2 h or more . In bivariate analysis differences were observed for age (15.5 +/- 24.2 vs 39.7 +/- 28.7 years; p < 0.01), temperature (38.7 +/- 1 vs 38 +/- 1.1 degrees C; p < 0.05), mean blood pressure (77 +/- 14 vs 91 +/- 20 mmHg; p < 0.05), headache (29% vs 75%; p < 0.01), meningeal signs (63% vs 19%; p < 0.01), skin lesions (60% vs 13%; p < 0.01), "sick" presentation (67% vs 19%; p < 0.01), performance of CT scan (8% vs 38%; p < 0.05) and appropriateness of management (96% vs 44%; p < 0.001) . In multivariate analysis only absence of skin lesions and inappropriate management remained significative . Mortality was higher when there was a delay of more than 2 h in antimicrobial therapy (25% vs 0%; p < 0.05) . CONCLUSIONS: Factors associated with delay of antimicrobial therapy were the absence of skin lesions and inappropriate management. Blood, 1998 Nov 15, 92(10), 3898 - 903 Inhibition of activation of the classical pathway of complement by human neutrophil defensins; van den Berg RH et al.; Defensins are small, cationic antimicrobial peptides that are present in the azurophilic granules of neutrophils . Earlier studies have shown that defensins may influence complement activation by specific interaction with activated C1, C1q, and C1-inhibitor . In the present study, we show that the defensin human neutrophil peptide-1 (HNP-1) is able to inhibit activation of the classical complement pathway by inhibition of C1q hemolytic activity . The binding site for HNP-1 on C1q is most likely located on the collagen-like stalks, as a clear, dose-dependent binding of HNP-1 to either intact C1q or to the collagen-like stalks of C1q was demonstrated using enzyme-linked immunosorbent assay (ELISA) . Besides binding of HNP-1 to C1q, also a limited binding to C1 and to a mixture of C1r and C1s was observed, whereas no binding to C1-inhibitor was found . Because binding of HNP-1 to C1-inhibitor has been suggested in earlier studies, we also assessed the binding of HNP-1 to mixtures of C1-inhibitor with either C1r/ C1s or C1 . No binding was found . Using a competition ELISA, it was found that HNP-1, but not protamine, inhibited binding of biotin-labeled HNP-1 to C1q in a dose-dependent fashion . In the fluid phase, preincubation of HNP-1 with C1q resulted in complex formation of HNP-1 and C1q and generation of stable complexes . In conclusion, HNP-1 is able to bind to C1q in the fluid phase and inhibits the classical complement pathway . This mechanism may be involved in the control of an inflammatory response in vivo. Scand J Rheumatol, 1998, 27(5), 323 - 8 Therapeutic aspects of spondyloarthropathies -- a review; Leirisalo-Repo M; In the pathogenesis of spondyloarthropathies, infection and gut inflammation are the most important external triggering factors . Early antimicrobial therapy to treat urethritis caused by Chlamydia trachomatis is effective in preventing a recurrent reactive arthritis . When the arthritis appear, a short term conventional antimicrobial therapy is unable to modify its course . In acute chlamydia arthritis, patients benefit from a prolonged (3-month) treatment with tetracycline, while such a treatment has not proved to be effective in enteroarthritis or in chronic forms of reactive arthritis . The role of sulfasalazine in the treatment of patients with spondyloarthropathies is controversial . It might modify the disease course during acute and chronic reactive arthritis, and is working for patients with ankylosing spondylitis, especially patients with peripheral arthritis . Data showing an effect of sulfasalazine in the prevention of chronic spondyloarthropathy or in modification of the long-term prognosis of ankylosing spondylitis are, however, lacking. Physiol Chem Phys Med NMR, 1998, 30(1), 1 - 13 Superoxide dismutase-like activity of metal substituted lactoferrin derivatives; Ishisaka R et al.; Lactoferrin (LF) is an iron-binding glycoprotein present in various secretions including milk and the specific granules of neutrophils . The main biological properties of this protein are thought to concern the regulation of iron absorption, antimicrobial activity and modulation of neutrophil activity . Copper bound LF (Cu-LF) inhibited the stimulation-dependent reduction of cytochrome c (Cyt . c) in guinea pig peritoneal neutrophils (GPMN) but were without effect on NADPH oxidase activity of the respiratory burst . However, Cu-LF stimulated the stimulation-dependent production of hydrogen peroxide as seen with superoxide dismutase (SOD) . Similar but weaker inhibition of Cyt . c reduction than that shown by Cu-LF was observed with manganese-LF (Mn-LF) but not with ferrous-LF (Fe-LF) or apo-LF (Apo-LF) . The inhibitory activity was concentration-dependent and the ID50s of Cu-LF and of Mn-LF were 0.1 and 5 microM, respectively . Reactive oxygen species (ROS) detected by luminol chemiluminescence (LCL) of stimulated-GPMN were partially inhibited by Cu-LF . Changes in LCL of stimulated GPMN induced by Cu-LF were similar to those of superoxide dismutase (SOD) . Thus, it is concluded that low concentrations of Cu-LF had SOD-like activity and high concentrations of Cu-LF inhibited the stimulation-dependent generation of ROS. Am J Respir Cell Mol Biol, 1998 Nov, 19(5), 721 - 7 Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response; Redecke V et al.; The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease . The alveolar macrophage (AM) is a potential target cell for the pathogen and may contribute to respiratory immunopathology . We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C . pneumoniae and AM from 12 healthy volunteers . Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR) . C . pneumoniae readily induced productive infection in the AM . Inclusions containing replicating pathogens could be maintained for up to 120 h . Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C . pneumoniae pneumonia . AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8 . ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated . Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C . pneumoniae pneumonia. Biochim Biophys Acta, 1998 Nov 10, 1376(3), 391 - 400 Magainins as paradigm for the mode of action of pore forming polypeptides; Matsuzaki K; Magainins are a class of antimicrobial peptides discovered in the skin of Xenopus laevis . The peptides kill bacteria by permeabilizing the cell membranes without exhibiting significant toxicity against mammalian cells, and are a promising candidate for a new antibiotic of therapeutic value . The main target of the peptides are considered to be the lipid matrix of the membranes . This review summarizes studies on magainin-lipid interactions in comparison with other pore forming peptides . The selective toxicity can be at least partly explained by preferential interactions of magainins with anionic phospholipids abundant in bacterial membranes . A novel mode of action is discussed in detail, i.e., the formation of a dynamic peptide-lipid supramolecular pore, which allows the mutually coupled transbilayer transport of ions, lipids, and peptides per se. J Biol Chem, 1998 Nov 13, 273(46), 30316 - 20 Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis; Heath RJ et al.; The broad spectrum antibacterial properties of 2-hydroxydiphenyl ethers have been appreciated for decades, and their use in consumer products is rapidly increasing . We identify the enoyl-acyl carrier protein reductase (fabI) component of the type II fatty acid synthase system as the specific cellular target for these antibacterials . Biologically active 2-hydroxydiphenyl ethers effectively inhibit fatty acid synthesis in vivo and FabI activity in vitro . Resistant mechanisms include up-regulation of fabI expression and spontaneously arising missense mutations in the fabI gene . These results contradict the view that these compounds directly disrupt membranes and suggest that their widespread use will select for resistant bacterial populations. J Invest Dermatol, 1998 Nov, 111(5), 739 - 43 Antimicrobial peptides: an emerging concept in cutaneous biology; Gallo RL et al.; Antimicrobial peptides are part of the host defense systems of plants, insects, fish, amphibia, birds, and mammals . These small proteins were previously thought of as an evolutionarily ancient system of immune protection with little relevance to the normal function of human skin . Recent developments have found that mammalian skin expresses these gene-encoded peptide antibiotics during inflammatory events such as wound repair, contact dermatitis, and psoriasis . The presence of these peptides in the skin forms a barrier for innate host protection against microbial pathogenesis . Furthermore, antimicrobial peptides also act on animal cells by stimulating them to change behaviors such as syndecan expression, chemotaxis, and chloride secretion . The combination of effects on host cells with antimicrobial action in a single molecule represents an efficient defense and response system against injury . Understanding the action of antimicrobial peptides in skin may yield further insight into the mechanism of innate cutaneous disease control and provide new approaches to therapy of wounds and inflammatory dermatitis. Int J Pediatr Otorhinolaryngol, 1998 Sep 15, 45(1), 41 - 6 Interobserver agreement in assessing plain radiographs of maxillary sinus; Fonseca MT et al.; Interrater agreement of six observers in interpreting maxillary sinus plain X-ray films was assessed . Patients aged 1-15 years old were enrolled and X-rays in the Caldwell and Waters's views were requested to confirm diagnosis of sinusitis or after antimicrobial therapy for a pre-existing sinusitis . One-hundred and one pairs of maxillary sinus radiographs from 101 patients were submitted to an independent and blind interpretation by three radiologists and three pediatricians . Each maxillary sinus was separately analyzed . Kappa statistic was used to measure interobserver agreement . A fair degree of agreement among the six raters was found on analyzing these films: 0.39 (95% CI, 0.36-0.41) for the right maxillary sinus and 0.37 (95% CI, 0.34-0.39) for the left one . These results stress literature data on the limits of plain radiographs for diagnosing maxillary sinusitis . The necessity of knowing the clinical findings while interpreting the exams also was depicted. Int J Dermatol, 1998 Oct, 37(10), 747 - 51 Drug eruptions in Bangkok: a 1-year study at Ramathibodi Hospital; Puavilai S et al.; BACKGROUND: As new drugs are introduced onto the market, it is important to determine those that can cause cutaneous reactions and with what frequency . In addition, drugs that have been used for a long period of time may cause new types of eruption that have not been observed previously . The purpose of this study was to evaluate the types of drug eruption and the causative agents in a hospital-based population for a period of 1 year . METHODS: All in- and outpatients consulting for drug eruptions at the Dermatology Clinic, Ramathibodi Hospital from June 1995 to May 1996 were included in the study . The history and physical examination were performed by one of the authors . In suspected cases, a skin biopsy was carried out to confirm the diagnosis . Rechallenge tests with suspected drugs were performed with informed consent . RESULTS: One hundred and thirty-two patients were enrolled in the study . The most common types of drug eruption were maculopapular eruption, fixed drug eruption, and urticaria . Antimicrobial agents were found to be the most common causative drugs, followed by antipyretic/anti-inflammatory agents and drugs acting on the central nervous system . CONCLUSIONS: Although the most common type of drug eruption and the most common causative agents were not different from those found in previous studies, the new generation of antibiotics and antifungal agents were found to be a frequent cause of drug eruptions . New types of drug eruption, such as generalized exanthematous pustulosis and acral erythema, were observed in this study. Microbiol Immunol, 1998, 42(9), 617 - 25 Immune control of Chlamydial growth in the human epithelial cell line RT4 involves multiple mechanisms that include nitric oxide induction, tryptophan catabolism and iron deprivation; Igietseme JU et al.; The antimicrobial activity of T cell-derived cytokines, especially interferon (IFN)-gamma, against intracellular pathogens, such as Chlamydia trachomatis, involves the induction of 3 major biochemical processes: tryptophan catabolism, nitric oxide (NO) induction and intracellular iron (Fe) deprivation . Since the epithelial cell is the natural target of chlamydial infection, the presence of these antimicrobial systems in the cell would suggest that they may be involved in T cell control of intracellular multiplication of Chlamydia . However, the controversy over whether these 3 antimicrobial processes are present in both mice and humans has precluded the assessment of the relative contribution of each of the 3 mechanisms to chlamydial inhibition in the same epithelial cell from either mice or humans . In the present study, we identified a Chlamydia-susceptible human epithelial cell line, RT4, that possesses the 3 antimicrobial systems, and we examined the role of nitric oxide (NO) induction, and deprivation of tryptophan or Fe in cytokine-induced inhibition of chlamydiae . It was found that the 3 antimicrobial systems contributed to cytokine-mediated inhibition of the intracellular growth of Chlamydia . NO induction accounted for approximately 20% of the growth inhibition; tryptophan catabolism contributed approximately 30%; iron deprivation was least effective; but the combination of the 3 systems accounted for greater than 60% of the inhibition observed . These results indicate that immune control of chlamydial growth in human epithelial cells may involve multiple mechanisms that include NO induction, tryptophan catabolism and Fe deprivation. Bioorg Med Chem, 1998 Sep, 6(9), 1597 - 604 Syntheses, biochemical and biological evaluation of staurosporine analogues from the microbial metabolite rebeccamycin; Anizon F et al.; The indolocarbazole antibiotics staurosporine and rebeccamycin (1) are potent antitumor drugs targeting protein kinase C and topoisomerase I, respectively . To obtain staurosporine analogues from rebeccamycin, different structural modifications were performed: coupling of the sugar moiety to the second indole nitrogen, dechlorination and then reduction of the imide function to amide . The newly synthesized compounds (3-6) were tested for their abilities to bind to DNA and to inhibit topoisomerase I and protein kinase C . Their antiproliferative effects in vitro against B16 melanoma and P388 leukemia (including the related P388CPT cell line resistant to camptothecin) as well as their anti-HIV-1 and antimicrobial activities against various strains of microorganisms were determined . The cytotoxicity of the dechlorinated imide analogue 5 correlates well with its DNA binding and anti-topoisomerase I activities . These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazoles equipped with a carbohydrate attached to the two indole nitrogens. Lancet, 1998 Jul 4, 352(9121), 58 - 61 Disease surveillance at district level: a model for developing countries; John TJ et al.; For over a decade we have maintained within a district of 5 million people, a system of prompt reporting of cases of childhood vaccine-preventable diseases, encephalitis, meningitis, hepatitis, and rabies; together with a sentinel laboratory surveillance of cholera, typhoid fever, malaria, HIV infection and antimicrobial-resistance patterns of selected pathogens . The system combined government and private sectors, with every hospital enrolled and participating . Reports were scanned daily on a computer for any clustering of cases . Interventions included investigations, immunisation, antimicrobial treatment, health education, and physical rehabilitation of children with paralysis . All vaccine-preventable diseases have declined markedly, whilst malaria and HIV infections have increased steadily . Annual expense was less than one US cent per head . The reasons for the success and sustainability of this model include simplicity or reporting procedure, low budget, private-sector participation, personal rapport with people in the network, regular feedback of information through a monthly bulletin, and the visible interventions consequent upon reporting . This district-level disease surveillance model is replicable in developing countries for evaluating polio eradication efforts, monitoring immunisation programmes, detecting outbreaks of old or new diseases, and for evaluating control measures. J Otolaryngol, 1998, 27 Suppl 2, 43 - 8 No therapy: use, abuse, efficacy, and morbidity--the European versus the Third-World experience; Rutka J et al.; OBJECTIVE: Historical controls documented a marked reduction in complications from acute otitis media (AOM) and chronic suppurative otitis media (CSOM) with the introduction of antibiotic therapy in the period 1930 to 1950s amongst other changes that occurred in North American and Western European society . Today, the natural history of spontaneous remission in AOM in over 80% of children within 24 hours of presentation questions the raison d'etre for the routine prescription of antibiotics for what may essentially be a self-limiting condition . Metaanalyses of numerous antibiotic versus placebo trials in the treatment of AOM have demonstrated little difference in clinical outcome, as have treatment stratagems where antibiotics have been initially withheld . More judicious use of antibiotic therapy in AOM appears to have been associated with a decline in antimicrobial resistance in countries such as the Netherlands and Iceland . It is difficult to know, however, whether the direct savings from decreased antibiotic use will ultimately lead to an actual decrease in the other direct and indirect costs associated with AOM . Unfortunately, children in the third world have not experienced a corresponding decline in ear disease . Significant loss of disability-adjusted life years (DALYs) continues to occur from otitis media . Withholding antibiotic therapy in the treatment of AOM would more than likely impose greater morbidity and mortality on an already disadvantaged population . Nevertheless, the experience of the Thai Rural Ear Nose and Throat Foundation has been seminal in documenting and affecting change in both the morbidity and mortality patterns of AOM and CSOM during Thailand's transition toward developed nation status . This article analyzes these issues and provides a review of the literature available. J Otolaryngol, 1998, 27 Suppl 2, 2 - 8 Acute otitis media: the evolution of surgical management; Friedberg J et al.; OBJECTIVE: Acute suppurative otitis media has been a common disease since time immemorial and, until the late nineteenth century, was followed by a high complication rate, major morbidity, and frequent mortality . Since then, the overall incidence of the disease has changed little; however, in less than a century, progressively more sophisticated surgery and the introduction of antimicrobials have reduced the mortality, at least in developed countries, to a rarity . Complications such as chronic perforation of the tympanic membrane or cholesteatoma, although much less frequent than in the past, are not uncommon . The evolution of mastoid surgery into the antibiotic era is reviewed . CONCLUSION: There is concern that with the increasing frequency of bacterial resistance to antibiotics and the decreasing familiarity of family practitioners with the clinical presentation of complicated otitis media that we may be faced with a resurgence of mastoid disease. Aust Fam Physician, 1998 Oct, 27(10), 890 - 4 Are new antibiotics on the horizon? Christiansen K. BACKGROUND: The development of new antimicrobials is driven by the emergence of resistant bacteria, a change in disease pattern such as that caused by opportunistic and nosocomial infections and a need for improved pharmacokinetics or reduced adverse reactions . OBJECTIVE: This article looks at the emerging resistances of significance in the 1990s and then at the new antibiotics that are either to be released or are under development . DISCUSSION: Although some of these antibiotics show great promise, their long term value will ultimately be determined by how appropriately they are used by the medical community. Clin Infect Dis, 1998 Oct, 27(4), 865 - 83 Novelties in the field of anti-infectives in 1997; Bryskier A; In 1997, more than 40 new medicinal chemical entities in the field of anti-infectives were presented during the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, held in Toronto . Among these novelties, three compounds could or will be candidates for clinical development: HMR 3647, a ketolide derivative; T-3811, a new quinolone; and GM 237,354, a new antifungal compound . Other molecules are potential lead compounds. Clin Infect Dis, 1998 Oct, 27(4), 711 - 3 Prolonged suppressive antibiotic therapy for infected orthopedic prostheses; Segreti J et al.; Prolonged suppressive antibiotic therapy may be an alternative to removal of infected orthopedic prostheses in some patients . However, the efficacy of prolonged suppressive antibiotics is not well established . We retrospectively reviewed 18 patients with infected orthopedic prostheses who had been treated with prolonged antimicrobial suppression during the last 10 years . Eighteen episodes of infection were identified in these 18 patients . There were nine men and nine women, and the mean age was 66 years (range, 31-83 years) . All patients had a functional prosthesis and were treated with surgical debridement, retention of the prosthesis, and administration of intravenous antibiotics for 6-8 weeks, followed by prolonged oral antibiotic suppression . Fifteen of the 18 patients appear to have had a good response and have been able to retain a functional prosthesis . Complications related to antibiotic suppression occurred in 22% but did not necessitate discontinuation of the antibiotic therapy . Prolonged antibiotic suppression is a reasonable alternative to surgery in selected patients with infected orthopedic prostheses. Arch Dis Child, 1998 Aug, 79(2), 149 - 52 Side to side comparison of topical treatment in atopic dermatitis; Ainley-Walker PF et al.; OBJECTIVES: To document and evaluate the outcome of side to side comparisons of different corticosteroids in determining the most effective topical treatment for individuals admitted to hospital for control of atopic dermatitis . METHODS: Retrospective case note study of 82 admissions (66 children) to a children's hospital for treatment of atopic dermatitis between 1 June 1993 and 31 October 1995 . Different topical corticosteroid ointments were applied to the two sides of the body . The outcome measure was a comparison between the two sides, to see whether one treatment was better than the other . RESULTS: More potent topical corticosteroid preparations appeared more effective than weaker preparations on 25 occasions, there was no difference on 20 occasions, and on seven occasions a weaker preparation appeared more effective . Incorporation of an antimicrobial agent did not appear to increase the efficacy of a preparation . CONCLUSIONS: The management of atopic dermatitis is bedevilled by considerable spontaneous fluctuations in severity, leading to uncertainty as to whether a new treatment is beneficial; a coincidental flare up of the skin lesions may be wrongly attributed to a particular treatment, which is then discarded . Comparing different topical treatments simultaneously on opposite sides of the body is a feasible and rational way to determine the optimum treatment for an individual with atopic dermatitis. Int J Clin Pract Suppl, 1998 Jun, 95, 14 - 22 Antimicrobial resistance in the intensive care unit: impact of new patterns; McGowan J Jr et al.; The effects of resistance are being observed on an increasing scale in the intensive care unit (ICU) . Multi-resistant organisms are diminishing our ability to treat and control the spread of infection . Strategies for the control of resistant organisms in the ICU must be based on the underlying pathophysiology of resistance mechanisms . Resistance is also influenced by the setting in which health care is provided . In the United States (US), changes in the health care delivery system have had a dramatic impact on the number and type of ICU patients . Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology) is a co-operative project to measure antibiotic resistance and antibiotic use . Results show a relative increase in the number of ICU beds in US hospitals . They also indicate a significant stepwise decrease in the percentage of resistant organisms isolated from ICU patients, non-ICU inpatients, and outpatients . These results suggest that resources allocated to control of antimicrobial resistance should continue to be focused on the hospital and particularly the ICU . Study findings also indicate that antimicrobial use and resistance are usually, but not always, linked . This means that strategies for dealing with resistance must address several additional factors including infection control practices, community burden of resistance, and possibly others . Thus national or regional guidelines for preventing resistance will have to be modified to take into account local care patterns, problems and resources . When dealing with resistance in the ICU, 'one size will not fit all'. Antimicrob Agents Chemother, 1998 Nov, 42(11), 3022 - 3 Antimicrobial susceptibilities of Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens spp . isolated in Spain; Andres MT et al.; The susceptibilities of 143 Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens isolates to 18 antimicrobial agents were tested . All P . gingivalis isolates were susceptible . In contrast, some Prevotella spp . (17%) were resistant to beta-lactams, erythromycin, clindamycin, or tetracycline and carried resistance genes, ermF or tetQ, or beta-lactamases. Antimicrob Agents Chemother, 1998 Nov, 42(11), 3002 - 5 Antimicrobial susceptibility of bacteria isolated from orthopedic implants following revision hip surgery; Tunney MM et al.; The susceptibilities of 49 isolates recovered from orthopedic implants to seven antimicrobial agents were evaluated by the broth microdilution method . Ciprofloxacin and vancomycin were more active than gentamicin, representing aminoglycosides which are routinely incorporated into bone cement, and also more active than the peroperative antimicrobial agents cefamandole and erythromycin . The use of ciprofloxacin and vancomycin in vivo, therefore, warrants further evaluation. Antimicrob Agents Chemother, 1998 Nov, 42(11), 2870 - 6 Subinhibitory concentrations of antimicrobial agents reduce the uptake of Legionella pneumophila into Acanthamoeba castellanii and U937 cells by altering the expression of virulence-associated antigens; Luck PC et al.; We determined the MICs of ampicillin, ciprofloxacin, erythromycin, imipenem, and rifampin for two clinical isolates of Legionella pneumophila serogroup 1 by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction assay and by quantitative culture . To test the influence of subinhibitory concentrations (sub-MICs) of antimicrobial agents on Legionella uptake into Acanthamoeba castellanii and U937 macrophage-like cells, both strains were pretreated with 0.25 MICs of the antibiotics for 24 h . In comparison to that for the untreated control, subinhibitory concentrations of antibiotics significantly reduced Legionella uptake into the host cells . Measurement of the binding of monoclonal antibodies against several Legionella antigens by enzyme-linked immunoassays indicated that sub-MIC antibiotic treatment reduced the expression of the macrophage infectivity potentiator protein (Mip), the Hsp 60 protein, the outer membrane protein (OmpM), an as-yet-uncharacterized protein of 55 kDa, and a few lipopolysaccharide (LPS) epitopes . In contrast, the expression of some LPS epitopes recognized by monoclonal antibodies 8/5 and 30/4 as well as a 45-kDa protein, a 58-kDa protein, and the major outer membrane protein (OmpS) remained unaffected. J Clin Periodontol, 1998 Oct, 25(10), 794 - 800 Clinical and antimicrobial effects of a single episode of subgingival irrigation with tetracycline HCl or chlorhexidine in deep periodontal pockets; Stabholz A et al.; 15 adults, each providing 4 non-adjacent untreated periodontal pockets with a probing depth (PD) exceeding 6 mm, volunteered for a randomized, split-mouth, double-blind, clinical study evaluating subgingival irrigation with chlorhexidine (CHX) or tetracycline HCl (TTC) . The study protocol included oral hygiene instructions followed by scaling and root planing . Experimental and immediately adjacent teeth did not receive instrumentation . The 4 deep periodontal pockets in each patient were assigned to be irrigated with 150 ml CHX (0.12%), TTC (10 or 50 mg/ml; TTC10, TTC50), or sterile saline (control) in a single episode . Post-irrigation mechanical plaque control was supported by 2x daily CHX rinses throughout the 12-week observation interval . Recordings of oral hygiene (P1I), gingival health (GI), bleeding on probing (BoP), probing depth (PD), clinical attachment level (CAL), and microbial morphotypes from subgingival paper point samples were performed pre-irrigation, and at 1, 2, 4, 6, 8, 10, and 12 weeks post-irrigation . Mean post-irrigation P1I was low, fluctuating between 0.0 and 0.4, without significant differences between experimental groups . Mean pre-irrigation GI approximated 1.4 and reached 0.8 at the exit of study without significant differences between experimental groups . All experimental sites exhibited BoP pre-irrigation . BoP was significantly reduced in TTC50 compared to TTC10, CHX and control sites from week 8 post-irrigation . PDs were reduced for the experimental groups with TTC50 exhibiting the strongest reduction . CALs remained unaltered from pre-irrigation for TTC10, CHX and control sites over the 12-week observation interval, whereas TTC50 sites consistently improved to significantly differ from all other groups at week 10 and 12 post-irrigation . The distribution of bacterial morphotypes was significantly altered towards one of periodontal health for all experimental groups with a profound effect for TTC50 sites . Our results suggest that subgingival irrigation with TTC solutions at high concentrations may have a role in the management of adult periodontitis. Eur J Clin Microbiol Infect Dis, 1998 Aug, 17(8), 587 - 90 Risk factors for bloodstream infections at a cancer center; Velasco E et al.; A hospital-based matched case-control study was conducted in order to identify risk factors for the development of bloodstream infections in adult hospitalized patients . Between January 1993 and December 1994, 264 episodes of bloodstream infection were evaluated . Significant variables identified by univariate analysis were included in a multivariate model that showed that central venous catheter {odds ratio (OR), 6.71}, poor performance status (OR, 3.40), weight loss (OR, 2.47), hematologic diseases (OR, 2.24), and previous antimicrobial therapy (OR, 2.12) independently influenced the outcome . The knowledge of modifiable risk factors is useful in the development of strategies that may contribute to the prevention of bloodstream infections. Int J Clin Pract Suppl, 1998 Jun, 95, 27 - 38 Economic impact of resistance in the community; Eandi M et al.; Antimicrobial resistance is assumed to be an important health problem and an economic burden to society . However, the relationship between the emergence of in vitro microbiological resistance and its clinical and socioeconomic consequences has not yet been satisfactorily determined for either nosocomial or community-acquired infection . In the case of both nosocomial and community-acquired infection, previous exhaustive reviews of published and unpublished reports concluded that mortality, likelihood of hospitalization, and length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria . However, evaluation of the economic impact of resistance is still problematic and the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified . Decision analysis models, such as decision trees, can aid evaluation of the impact of resistance on health and economic outcomes from the perspective of a given decision maker . A model of cost analysis should be based on a knowledge of the incremental consumption of resources specifically dependent on the dynamics of antimicrobial resistance in a given clinical setting (e.g . home care or hospital care) . In general, we can assume that the increased rate of isolation of resistant strains from community-acquired infections correlates positively with an increase in morbidity, mortality, risk of hospitalization and the need for additional days in hospital and for more expensive and powerful antibiotics . We implemented and simulated a general decision-tree model to analyse the influence of antibiotic resistance on the economic outcomes of community-acquired lower respiratory tract infections, from the perspective of both society and the health-care local organization (HCLO) . This model allows simulation of the impact of different degrees of resistance on the direct costs of an antibiotic therapy as well as on the cost-effectiveness of antibiotics with different degrees of resistance. Int J Clin Pract Suppl, 1998 Jun, 95, 9 - 13 Resistance in hospitals: implications for empiric choice of therapy; Masterton R; Although some organisms were resistant to antimicrobial agents before such compounds were introduced into clinical practice, it is only since this occurred that the breadth, depth and complexity of this problem has developed . The early acceleration in the production of antimicrobial substances was uniformly matched by the observation of correspondingly resistant organisms . This article reviews whether the presence of antimicrobial resistance in hospitals should have implications for the empiric choice of such therapy . It is shown that although not an absolute, antimicrobial usage is directly reflected in the presence and nature of resistance with both indirect and direct effects . These resistance patterns have been demonstrated to alter the clinical outcome surrounding sepsis care in hospital patients where the key feature is to actually initiate management with an appropriate agent . It is less clear from the available data whether the control of antimicrobials within hospitals can prospectively influence the sustained susceptibility of organisms to the agents being used . The need for locally determined programmes to respond to the threat of hospital antimicrobial resistance development is highlighted . Attention is drawn to the essential interaction between such schemes and related issues such as infection control and microbiological surveillance. Int J Clin Pract Suppl, 1998 Jun, 95, 4 - 8 Outpatient parenteral antimicrobial therapy as an alternative to hospitalization; Tice A; Outpatient parenteral antimicrobial therapy (OPAT) has evolved because of advances in antibiotics and the advent of new technology . It provides a cost-effective means of treating seriously infected patients away from hospital . Virtually any infection can be treated on an outpatient basis and several treatment programmes have been designed . Housebound patients can be visited by a nurse who will supervise administration; infusion centres, set up in a clinic or a doctor's office, provide on-hand medical staff and the benefit of a medical facility; self-administration provides autonomy for patient and family and is the least costly . Given the cost-cutting environment in which healthcare now operates worldwide, it is important that OPAT must develop its own procedures and guidelines for quality assurance . For OPAT to work away from the controlled environment of the hospital, it is essential that physicians, nurses and pharmacists adapt to new medical environments and work with the patient to ensure that care is maintained to a high standard. Nippon Rinsho, 1998 Oct, 56(10), 2718 - 29 {Status of emerging drug resistance in Shiga toxin-producing Escherichia coli in Japan during 1996: a minireview}; Yamamoto T et al.; A total of 192 Shiga toxin-producing Escherichia coli (STEC) strains isolated from the 1996 episodes in Japan were tested for their in vitro susceptibilities to 41 antimicrobial agents . Drug resistance was found with kanamycin, tetracycline, nalidixic acid, ampicillin, streptomycin, sulfamethoxazole, and fosfomycin . The expression of fosfomycin resistance was greatly dependent on culture conditions and resistance was detected (e.g.) when Mueller-Hinton agar or nutrient agar supplemented with horse blood (or glucose-6-phosphate) was used as test media . All the STEC strains belonging to serotype O26 exhibited fosfomycin resistance . Multiple drug-resistant strains spread 8 of 18 prefectures examined . Out of eleven O157: H7 outbreaks, only one outbreak revealed infections due to multiple drug-resistant strains which carried an R plasmid . Tetracycline, streptomycin, and sulfamethoxazole resistance, which was previously described with O157: H7 strains isolated from a large outbreak as well as sporadic cases in the United States, were also found in Japan with human and bovine isolates (but not with porcine isolates) . In contrast, the STEC strains were highly susceptible to newer quinolones, cephems, trimethoprim, gentamicin, and azithromycin . No drug resistance was observed with dibekacin and minocycline. Am J Infect Control, 1998 Oct, 26(5), 507 - 12 Development and evaluation of a new alcohol-based surgical hand scrub formulation with persistent antimicrobial characteristics and brushless application; Hobson DW et al.; BACKGROUND: Since the introduction in the 1970s of surgical hand scrub formulations that contain 4% chlorhexidine gluconate (CHG), new surgical scrub formulations that have improved efficacy, persistence, or significantly improved use characteristics have not been forthcoming . In addition, the manufacturer's labeling for popular hand scrub products generally requires scrub times in excess of 6 minutes, whereas current practical needs call for products with substantially shorter scrub times . A new alcohol-based surgical scrub formulation, which has ingredients that provide emollient, surfactant, and antimicrobial persistence characteristics to complement the rapid and broad-spectrum antiseptic qualities of alcohol, has been developed in an effort to address these current practical needs . METHODS: The relative efficacy of a new alcohol-based surgical scrub formulation that contains ingredients that provide surfactant and antimicrobial persistence characteristics was compared with that of commercial 4% CHG and 7.5% povidone iodine (PVPI) formulations with use of human subjects . Hand antimicrobial count sampling was performed by using standardized "glove juice" methodology . RESULTS: The efficacy and persistence results of the new formulation showed statistically significant improvement over both CHG and PVPI at a substantially lessened scrub time (3 minutes) . In addition, use of the new formulation without a scrub brush produced results statistically similar to 3-minute applications with either a brush or a sponge . CONCLUSIONS: The new alcohol-based formulation demonstrates promise as a new surgical hand scrub formulation with antimicrobial and use characteristics that are significantly improved over current CHG and PVPI formulations . These studies demonstrate the suitability of this formulation for use as a surgical hand scrub and for brushless application. Am J Infect Control, 1998 Oct, 26(5), 488 - 94 Povidone iodine gel alcohol: a 30-second, onetime application preoperative skin preparation; Jeng DK et al.; BACKGROUND: Simplifying and shortening the skin-preparation application procedure is desirable for many reasons, which include labor-cost savings and improved suite utilization . A new formulation, PVP-I Gel Alcohol (PGA) that contains 5% PVP-I and 62% ethanol in gel form, was developed to achieve a shorter preparation time with a rapid and persistent efficacy on a broad spectrum of microorganisms and to minimize the potential for iodine irritation . METHOD: The test methods outlined in the Federal Register, 21 CFR Parts 333 and 369, "Tentative Final Monograph for Health-Care Antiseptic Drug Products;" Proposed Rule, 1994 (Monograph), were adapted in this study . Efficacy of PGA was evaluated, both in vitro and in vivo . The in vitro time-kill and minimum inhibition concentration tests were conducted by using 33 strains of aerobic and anaerobic gram-positive bacteria, gram-negative bacteria, yeasts, and antibiotic-resistant bacteria . In the clinical test, the inguinal and abdominal skin sites of human subjects were exposed to PGA for 30 seconds to assess the antimicrobial efficacy on normal skin flora . Betadine PVP-I scrub was tested in a 5-minute application as a control . RESULTS: The time-kill test showed that PGA delivered a rapid antimicrobial activity--reducing greater than 3 to 8 log microorganisms in 15 seconds in all of the 33 species of microorganisms tested . Within 30 seconds, all challenge organisms were reduced below detection level . Results of the minimum inhibition concentration test showed that PGA demonstrated an equivalent activity to Betadine control under the testing conditions . In the clinical test, PGA was effective in the reduction of greater than 3 log and 2 log of normal skin flora, respectively, in inguinal and abdominal sites in a single-step 30-second application . Bacteria levels remained significantly below the baseline for 6 hours in the primary study and for 24 hours in a secondary study . These results show that the current PGA formulation with a 30-second application delivers an efficacy equivalent to Betadine scrub in a 5-minute application and that the PGA formulation has a long-lasting effect--up to 24 hours . CONCLUSION: The PGA formulation delivered rapid and persistent antimicrobial activity against a broad spectrum of bacteria both in vitro and in vivo . PGA is an effective skin-preparation formulation for use in a single-step 30-second application. Boll Chim Farm, 1998 Jul-Aug, 137(7), 267 - 76 Synthesis and in vitro antimicrobial and antitumoral screening of novel lipophilic isoniazid analogues . VI; Vigorita MG et al.; Various kinds of lipophilic analogues of isonicotinic acid hydrazide (Isoniazid) were synthesized and in vitro explored in a search for antimycobacterial agents with extended activity spectrum against pathogens responsible for the AIDS-associated diseases . The primary in vitro screening showed that a) isonicotinoylhydrazones 1a, 1b, 1d, 1e are more active than the parent drug against non-tubercular mycobacteria (MIC ranging between 0.5 and 4 micrograms/ml), b) isonicotinohydrazides 6b and 6e display interesting antibacterial activity on some Gram + and Gram-strains, and c) trifluoromethyl-containing compounds 1a and 2c inhibit the growth of several human tumor cell lines at doses between 10(-5) and 10(-6) M . On the contrary, none of the tested analogues significantly counteracts the cytopathogenicity induced by HIV and HSV viruses. Acta Gastroenterol Belg, 1998 Jul-Sep, 61(3), 357 - 66 Antimicrobial resistance in Helicobacter pylori: a global overview; Glupczynski Y; Helicobacter pylori resistance to antimicrobial agents is of particular concern because it is a major determinant in the failure of eradication regimens . Antimicrobial drug resistance has been reported to occur for nitroimidazoles, macrolides, fluoroquinolones, rifampin and tetracyclines . Resistance to nitroimidazoles is the most common, in the range of 30-40% on the average in Europe while the overall prevalence rate of resistance to macrolides is lower, probably ranging between 2-10% in most countries . Development of secondary (acquired) resistance to nitroimidazoles and to the macrolides usually occurs as a rule (> 70-100%) in case of failed eradication therapy . Data available from several centres seems however to indicate that a significant shift towards increasing resistance to metronidazole and to the macrolides might have possibly occurred in many countries over the last years . Resistances to both metronidazole and to clarithromycin are the most significant ones because they influence the success of the treatments although this seems to be less marked and more dependent on the treatment regimens considered in the case of metronidazole resistance than in the setting of clarithromycin resistance . These differences may in part relate to methodological variations and to the inherent difficulties in assessing the susceptibility of H . pylori to metronidazole . It is possible that different resistance cut-off might also have to be considered for metronidazole depending on the treatment regimens administered . The mechanisms of resistance have been well defined for the macrolides and are beginning to be unraveled for the nitroimidazoles . In all cases, resistance of H . pylori to antimicrobial agent seems to be due to the development of single mutational events in chromosomal genes rather than to the acquisition of exogenous resistance genes . Owing to the restricted ability of microbiology laboratories with expertise in H . pylori culture and the lack of standardised methodology for susceptibility testing, H . pylori culture is not often performed routinely . It should however be considered after documented treatment failure or in patients from a geographic area or of an ethnic origin with higher likelihood of antimicrobial drug resistance . Likewise it is deemed very important to institute national and regional surveillance programs to follow the evolution of H . pylori resistance and to better adapt treatment regimens to changes in resistance patterns. Acta Gastroenterol Belg, 1998 Jul-Sep, 61(3), 336 - 43 How (who?) and when to test or retest for H . pylori; Burette A; Several direct/invasive and indirect/non-invasive diagnostic tests are available for the diagnosis of H . pylori infection . Invasive tests require biopsy sampling of the gastric mucosa and include rapid urease test, histology, bacterial culture and polymerase chain reaction technique . Non-invasive tests include the urea breath test and serological assays . This review gives a critical comparative analysis of accuracy, advantages and limitations of the different diagnostic tests including current cost and availability in Belgium . Rapid urease testing (RUT) of gastric biopsy specimens is probably the initial test of choice in patients undergoing endoscopy because of its low cost, rapid availability of results, simplicity and accuracy . Histological examination of gastric biopsy samples should be mandatory at the initial presentation of the patient because it also gives insight on the status of the gastric mucosa (inflammation & premalignant changes) . Although not mandatory for primary diagnosis, a biopsy for culture and sensitivity testing should always be obtained when it is available and when endoscopy is undertaken as part of the patient's management . Among the non-invasive tests, the place of serology remains questionable for other than epidemiological purposes . How is H . pylori infection best diagnosed? How many tests are needed in routine clinical practice? The answer will depends on the clinical setting and local availability of the tests . For primary diagnosis in dyspeptic patients--where endoscopy is an important tool--a biopsy-based detection system is appropriate an we recommend the use of at least two diagnostic tests based on different principles, like RUT (with 1 or 2 biopsy specimen/test) and histology (including antrum & corpus biopsies) which are widely available . Alternatively a urea breath test may also be recommended when endoscopy is not required . Post-treatment monitoring seems to be justified in most cases and must always be performed at least 4-6 weeks after completion of therapy . The urea breath test is probably the method of choice for non-invasive testing in this clinical setting . When endoscopy is required, multiple biopsy specimens both from the antrum and the corpus and the use of at least two different diagnostic methods must be performed . Whenever possible, culture should always be done as it is very specific and allows testing of antimicrobial susceptibility which is mandatory in case of treatment failures . Neither the "Test and Treat" nor the "Test and Scope" strategies have been investigated in terms of effectiveness of symptoms relief and cost in Belgium and cannot therefore be recommended at this time. Rev Esp Quimioter, 1998 Sep, 11(3), 205 - 15 {Bacteremia caused by Stenotrophomonas maltophilia: a clinical-epidemiological study and resistance profile}; Ubeda P et al.; Over a 7-year period (1990-1996), the causal disease, predisposing factors, focus infection, clinical manifestations, complications and evolution of patients presenting bacteremia from Stenotrophomonas maltophilia were analyzed retrospectively in a university hospital . A microbiological study was carried out to determine the percentage of positive blood cultures per episode and the characteristics of bacteremia and to evaluate the antibiotic susceptibility of the isolated strains . Twenty-seven episodes of bacteremia from S . maltophilia were identified in 26 patients, half of whom were women, and the median age was 40 years . A total of 48% of the patients had blood malignancy (12 cases), with acute myeloid leukemia (5 cases) being the most frequent . Seven patients (27%) needed to be admitted to an intensive care unit for some type of vital support and/or intensive treatment . The previous administration of large spectrum antimicrobials (21/26) and the presence of a catheter or central catheter (19/26) were the most frequently found predisposing factors (81% and 73%, respectively) . One-quarter of the patients had received treatment with carbapenems . Immunodepression caused by chemotherapy or corticosteroids occurred in 65% of the cases . Half of the patients had undergone a major surgical procedure or had been intubated and submitted to mechanical ventilation . One-third presented granulocytopenia on the detection of bacteremia and 6 of the 12 patients with blood malignancy showed severe neutropenia (<500 neutrophils/mm3) . The bacteremia was acquired in hospital in 78% of the cases (21/27) . In 26% of these cases, S . maltophilia was diagnosed as the probable cause of bacteremia; in 34% this was just a possibility . The origin of the bacteremia was unknown in 11 cases (40%) . Infection from the vascular catheter was the most frequent focus infection (7 cases) . An average of 3.6 blood cultures were performed per patient, out of a total of 92, and 54% showed positive . The average time of growth for S . maltophilia in the blood culture bottles was 30 hours . One-third of the bacteremia episodes from S . maltophilia were polymicrobial (9/27) . Clinical evolution was favorable in 18 patients, while 8 died (31%), 5 cases (20%) from causes directly related to the bacteremia (4 from septic shock) . The mortality associated with the polymicrobial bacteremia was not significantly different from that for single microbial bacteremia from S . maltophilia . Ninety percent of the isolated strains showed susceptibility to co-trimoxazole, 77% to ticarcillin-clavulanic acid, 60% to ciprofloxacin, 62% to ceftazidime, 20% to amikacin and just 18% to imipenem. Rev Esp Quimioter, 1998 Mar, 11(1), 58 - 63 {Geographical distribution and evolution characteristics in outpatient consumption of quinolones in spain and by province (1985-1993).}; Tovar MR et al.; The use of quinolones has increased remarkably in recent years . Monitoring the trends in the consumption of these antibiotics is essential for the assessment of bacterial resistance . Sales figures for this group of antibiotics for each province from 1985 through 1993 were obtained from the medication database at the Spanish Ministry of Health . The consumption in milligrams per inhabitant older than 15 were calculated for each province and year . Specific time trends in consumption for Spain were studied and provincial maps were made representing consumption in milligrams per person older than 15 . Outpatient prescriptions of quinolones increased 155% between 1985 and 1993 in Spain, more than 2 tons per year . Seven of the eight provinces in Andalucia were among the ten provinces with greater consumption . A south-north pattern was detected from year to year . Important increases were observed in all the Spanish provinces . Further studies should consider this fact in the monitoring of antimicrobial resistance and should assess if provincial differences in consumption correlate with the prevalence of the infectious diseases treated with this group of antibiotics. Biochim Biophys Acta, 1998 Oct 23, 1425(2), 361 - 8 Biological characterization of a novel mammalian antimicrobial peptide; Gennaro R et al.; A putative antimicrobial peptide of 34 residues was recently deduced from a bovine cathelicidin gene sequence and named BMAP-34 . A peptide based on the deduced sequence was chemically synthesized and used to study the localization, structure and biological activities of BMAP-34 . A Western blot analysis using antibodies raised to the synthetic peptide showed that BMAP-34 is stored as proform in the cytoplasmic granules of bovine neutrophils . CD spectroscopy indicates that the peptide assumes an amphipathic alpha-helical conformation, as also predicted by secondary structure analysis . The peptide exerts a broad spectrum antimicrobial activity against both Gram-negative and Gram-positive organisms, and is not active against eukaryotic cells . When tested on Escherichia coli ML-35, the kinetics of bacterial killing and of inner membrane permeabilization are slower than those observed for other alpha-helical peptides derived from cathelicidins. Eur J Pharm Biopharm, 1998 Sep, 46(2), 215 - 21 Accumulation of sunscreens and other compounds in keratinous substrates; Hagedorn-Leweke U et al.; Several cosmetic ingredients, especially sunscreens, should be substantive, which means they are to be adsorbed to specific binding sites within the upper skin layers, particularly keratinized structures of the stratum corneum, and thus show resistance to washing off . We investigated the affinity of 10 non-ionic compounds, among these UV-absorbing chemicals, antioxidants, antimicrobial compounds and a repellent to animal keratin and human callus . In each case a linear relationship between the drug amount, which has accumulated in the respective keratin, and the remaining free concentration of the applied solution could be established . Moreover, drug affinities to keratinous substrates are in direct proportion to the octanol/vehicle partition coefficients, pointing to the fact, that drug enrichment in keratinic substrates is clearly governed by lipophilicity, while specific adsorption, i.e . genuine substantivity, does not seem to occur . After application of a saturated solution non-ionic compounds with a pronounced keratin/vehicle partition coefficient will build up the highest concentration within the stratum corneum . If these compounds show, at the same time, a high solubility in the vehicle, they will penetrate the skin most easily . The used callous tissue seems to be a suitable substrate to simulate and quantify solute uptake into human skin. J Heart Valve Dis, 1998 Sep, 7(5), 531 - 3 Definitive cure of recurrent prosthetic endocarditis using silver-coated St . Jude Medical heart valves: a preliminary case report; Carrel T et al.; Despite progress in the area of antimicrobial treatment and the surgical use of homografts, prosthetic valve endocarditis (PVE) remains one of the most dangerous complications following heart valve replacement . We present the case of a patient treated for acute endocarditis which affected the mitral valve and who developed recurrent PVE and native aortic valve endocarditis . After multiple valve surgery, the infection was controlled following aortic and mitral valve replacement using silver-coated prostheses . The St . Jude Medical (SJM) mechanical heart valve Masters Series with Silzone coating is intended to protect heart valve patients against microbial infection . The Silzone coating is formed by an ion beam-assisted deposition process that incorporates silver into the sewing cuff of the SJM heart valve . It has also been suggested that silver treatment may improve the healing characteristics of the heart valve sewing cuff . This technology may be a valuable option to prevent or cure PVE, in addition to homografts . Although the present patient is an isolated case, it was encouraging to find not only a well-healed mitral valve silver-coated prosthesis but also no persistent or recurrent infection during a nine-month follow up. Postgrad Med, 1998 Oct, 104(4), 119 - 22, 125-6 How do the newer oral antimicrobials stack up against traditional agents? Gleckman R, De La Rosa G. As the antibiotic arsenal expands with the development of new oral agents, selecting appropriate therapy is becoming more difficult . What are the therapeutic indications for the newer antimicrobials, and what advantages do they have over traditional agents? Drs Gleckman and De La Rosa discuss current issues related to antibiotic treatment and offer specific recommendations for the best use of the newer agents. Arch Pharm (Weinheim), 1998 Sep, 331(9), 294 - 6 Synthesis and antimicrobial activity of a dihydroampicillin and a dihydrocephalexin; Hashem AI et al.; A dihydroampicillin (3) and a dihydrocephalexin (4) have been synthesized by condensing alpha-(cyclohexa-1, 3-dienyl)glycyl chloride with 6-aminopenicillanic acid (1) and 7-deacetoxycephalosporanic acid (2) respectively . The two antibiotics obtained show enhanced antimicrobial activity towards certain bacterial strains compared with ampicillin and cephalexin. Lik Sprava, 1998 Jul-Aug, (5), 133 - 6 {The effect of a combined transplant on reparative osteogenesis in experimental bone defects of the jaw (the immediate results)}; Borysenko AV et al.; A combined transplant consisting of bone flour plus the sorption-antimicrobial complex polymethylsiloxane + furazolidone + metronidazole is proposed to be grafted into the bone periodontal pockets in patients with generalized parodontitis . Effects were studied of the above transplant on the experimental defects of the lower jaw--of albino rats (n = 36) . Morphologic changes in the immediate periods of follow-up (at day 7, 14, and 21) were characterized by a poorly manifest and short-term reactive inflammatory process in the paratransplant tissues as well as by an earlier development of the osteoid tissue and early formation of the bone regenerate. Presse Med, 1998 Sep 19, 27(27), 1371 - 5 {Impact of a multidisciplinary approach for monitoring prescribing of antibiotics in a hospital}; Causse R et al.; OBJECTIVE: The aim of this study was to examine the impact of a rationalized antibiotic prescription program in a 600-bed hospital . PATIENTS AND METHODS: The program was based on a local consensus policy, developed with the prescribers themselves, together with individual nominative dispensing (IDN) of the most costly antibiotics, and training/information programs aimed at institutional prescribers . The impact of the program was assessed in terms of the relevance of prescriptions (6-monthly audits), changes in the overall cost of anti-infectives, the average daily cost per hospital patient, and changes in the pattern of antimicrobial resistance among pathogens isolated in the institution . RESULTS: Reference recommendations were established for most clinical settings encountered in the hospital (104 for adults, 78 for children) . The four audits conducted since June 1996 show that the rate of unjustified prescriptions has remained below 6% . The cost of antimicrobials has fallen regularly, both in absolute terms and as a proportion of total drug costs . Finally, resistance rates among the different pathogens studied have fallen or remained stable . CONCLUSION: Rationalization of antimicrobial chemotherapy in a short-stay hospital necessitates an institution-based policy with long-term objectives, a large initial investment and, above all, a participative approach among all prescribers. FEMS Immunol Med Microbiol, 1998 Sep, 22(1-2), 163 - 8 Animal models of pneumocystosis; Dei-Cas E et al.; As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research . The parasite was reported in numerous mammals but P . carinii pneumonia (PCP) experimental models were essentially developed by using rats, mice, rabbits and ferrets . The rat treated with corticosteroids for 9-12 weeks is a useful PCP model . Like laboratory rats, conventional mice develop PCP after prolonged corticosteroid administration . The ferret (Mustela putorius furo) also develop PCP under corticosteroid regime . Whilst bronchoalveolar lavage (BAL) is really difficult to perform on live laboratory rodents, serial BAL sampling can be performed on live ferrets . Rabbits currently develop spontaneous PCP at weaning without corticosteroid administration . For this reason this model has been used for studying the host immune response as well as Pneumocystis-surfactant interactions . Pigs and horses also develop spontaneous PCP . Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model . Pneumocystis was detected in many non-human primates . Primates could represent a source of parasites taxonomically related to P . carinii sp . f . hominis . Moreover, primates might be used as experimental hosts to human Pneumocystis . A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are important drawbacks of the corticosteroid-treated models . For these reasons, inoculated animal models of PCP were developed . The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis infections . Extensive PCP can be obtained within 5-7 weeks, whilst 9-12 weeks are needed in the classical model . The severe combined immunodeficiency (SCID) mouse inoculated by nasal route and the athymic nude rats intratracheally inoculated were used to test the infectivity of Pneumocystis samples coming from cultures or from different hosts . They were also used to test the anti-Pneumocystis activity of antimicrobial molecules. Biochem Biophys Res Commun, 1998 Oct 29, 251(3), 775 - 83 Human natural resistance-associated macrophage protein 2: gene cloning and protein identification; Kishi F et al.; The Lsh/Ity/Bcg locus in the mouse genome regulates macrophage activation for antimicrobial activity against intracellular pathogens, and mouse Nramp1 (natural resistance-associated macrophage protein) gene was isolated as its candidate . The human NRAMP1 gene was subsequently isolated and its gene product was identified in macrophage/monocyte cells . Recently, a second Nramp gene, Nramp2, was found in mouse and human genomes . In the present study, we report the cloning and characterization of the human NRAMP2 gene, which is approximately 42 kb in length, containing 16 exons . The transcription start site was determined by 5'-RACE method, and the promoter was located between -246 bp to 145 bp in a region relative to the transcription start site, able to drive the luciferase reporter gene in HeLa cells . We also raised a polyclonal antibody against the glutathione S-transferase fusion protein containing the NH2-terminal 86 amino acids of human NRAMP2 . The protein product of the human NRAMP2 gene is apparently present in human cultured cell lines as a 64 kDa protein recognized by this antibody, which is consistent with the molecular mass deduced from the human NRAMP2 cDNA . Biochem Biophys Res Commun, 1998 Oct 9, 251(1), 67 - 70 CYP81E1, a cytochrome P450 cDNA of licorice (Glycyrrhiza echinata L.), encodes isoflavone 2'-hydroxylase; Akashi T et al.; The microsome of yeast cells overexpressing CYP81E1, a cytochrome P450 cDNA recently cloned from licorice (Glycyrrhiza echinata L., Fabaceae), catalyzed the hydroxylation of isoflavones, daidzein and formononetin, to yield 2'-hydroxyisoflavones, 2'-hydroxydaidzein, and 2'-hydroxyformononetin, respectively . The chemical structures of the reaction products were confirmed by mass spectrometric analysis . Genistein also yielded a putative 2'-hydroxylated product, but flavanones and cinnamic acid derivatives were not used as substrates for the reaction with the recombinant yeast microsome . CYP81E1 protein was thus demonstrated for the first time to be isoflavone 2'-hydroxylase involved in the biosynthesis of isoflavonoid-derived antimicrobial compounds of legumes . Cell Immunol, 1998 Nov 1, 189(2), 107 - 15 Cytotoxicity and apoptosis mediated by two peptides of innate immunity; Risso A et al.; Antimicrobial peptides are present in a wide range of species, from protozoa to man, as effector molecules of innate immunity . Several bovine precursors of antimicrobial peptides have recently been identified, as deduced from cDNA, and assigned to the cathelicidin family . Two of these are the proforms of the antimicrobial peptides BMAP-27 and BMAP-28, which share a similar amino acid sequence, structural conformation, and toxic activity toward several bacterial and fungal strains . Here we report that they are cytotoxic to human tumor cells and normal proliferating, but not resting, lymphocytes at concentrations comparable to those microbiocidal . This effect is primarily due to damage of plasma membrane integrity . A more detailed investigation of the U937 cell line revealed that a Ca2+ influx into the cytosol occurs in the early steps of permeabilization . The perturbation of the membrane structure and the Ca2+ influx are followed by programmed death . A similar apoptosis inducing effect is also observed on in vitro activated human lymphocytes . Biochemistry, 1998 Oct 27, 37(43), 15144 - 53 Mechanism of synergism between antimicrobial peptides magainin 2 and PGLa; Matsuzaki K et al.; The antimicrobial peptides magainin 2 and PGLa, discovered in the skin of the African clawed frog, Xenopus laevis, exhibit marked synergism {Westerhoff, H . V., Zasloff, M., Rosner, J . L., Hendler, R . W., de Waal, A., Vaz Gomes, A., Jongsma, A . P . M., Riethorst, A., and Juretic, D., Eur . J . Biochem . 228, 257-264 (1995)}, although the mechanism is not yet clear . They are believed to kill bacteria by permeabilizing membranes . In this study, we examined the interactions of these peptides in lipid bilayers . PGLa, like magainin 2, preferentially interacts with acidic lipids, forming an amphipathic helix . The peptide induces the release of a water-soluble dye, calcein, entrapped within liposomes . The coexistence of magainin 2 enhances membrane permeabilization, which is maximal at a 1:1 molar ratio . Fluorescence experiments using L18W-PGLa revealed that both peptides form a stoichiometric 1:1 complex in the membrane phase with an association free energy of -15 kJ/mol . Single amino acid mutations in magainin 2 significantly altered the synergistic activity, suggesting that precise molecular recognition is involved in complex formation . The complex as well as each component peptide form peptide-lipid supramolecular complex pores, which mediate the mutually coupled transbilayer transport of dye, lipid, and the peptide per se . The rate of pore formation rate is in the order complex >/= PGLa > magainin 2, whereas the pore lifetime is in the order magainin 2 > complex > PGLa . Therefore, the synergism is a consequence of the formation of a potent heterosupramolecular complex, which is characterized by fast pore formation and moderate pore stability. J Med Microbiol, 1998 Oct, 47(10), 889 - 91 A case-control study of diarrhoea in children caused by Escherichia coli producing heat-stable enterotoxin (EAST-1); Vila J et al.; Escherichia coli strains associated with diarrhoeal disease have been classified into several types according to the pathogenic mechanism . Among these, enteroaggregative E . coli strains (EAggEC) have been associated with persistent childhood diarrhoea . Some strains of EAggEC produce a heat-stable toxin (EAST-1) that differs from others described previously . The main goal of this case-control study was to determine the prevalence of EAggEC and EAST-1-producing E . coli strains as a cause of diarrhoea in children in Spain and to study their in-vitro susceptibility to 21 antimicrobial agents . In the case group (115 children) 22 (19%) isolates and four (3.5%) isolates were EAST-1-producing E . coli and EAggEC, respectively, whereas in the control group (79 children) four (5%) isolates produced EAST-1 (p = 0.005) and three (3.8%) isolates were EAggEC . The present study suggests that EAST-1-producing E . coli strains are associated with diarrhoeal diseases in Spanish children, whereas EAggEC strains are not . Moreover, EAST-1-producing E . coli strains showed a high susceptibility to all the antimicrobial agents tested except for ampicillin. Allergy, 1998 Sep, 53(9), 880 - 4 Atopy and intolerance of antimicrobial drugs increase the risk of reactions to acetaminophen and nimesulide in patients allergic to nonsteroidal anti-inflammatory drugs; Pastorello EA et al.; This study evaluated the risk factors for developing allergic reactions to alternative drugs such as acetaminophen and nimesulide in 367 patients intolerant of nonsteroidal anti-inflammatory drugs (NSAID) compared to 243 healthy controls . All subjects were given test doses (TD) of acetaminophen and nimesulide, and age, sex, atopy, and history of reactions also to unrelated drugs were compared in those who reacted and those who were tolerant of the challenge . TD was positive in 49 of 367 (14%) NSAID-allergic patients and in one (0.4%) of the controls (P<0.001) . No difference was found in age and sex between the TD-positive and TD-negative subjects, although a significantly larger number of females were NSAID allergic (P<0.01) . Of the 367 patients, 208 had a history of reactions only to NSAID, and 148 to NSAID and antimicrobial drugs (AMD) . TD with acetaminophen or nimesulide was positive in 6% of patients intolerant only of NSAID and in 24% of those intolerant of both NSAID and AMD, with an odds ratio of 4.82 . Atopy was more frequent among patients (36%) than controls (23%) (P=0.004), among TD-positive (51%) than TD-negative patients (33.5%) (P<0.02), and among patients intolerant of NSAID and AMD (48%) than those intolerant only of NSAID (P=0.006) . The odds ratios were, respectively, 1.87, 2.57, and 3.16 . This study provides evidence that atopy and history of allergic reactions to AMD increase the likelihood of intolerance of usually well-tolerated alternative drugs such as acetaminophen and nimesulide in subjects allergic to NSAID. Toxicol Lett, 1998 Sep 15, 98(3), 169 - 79 Study of cytotoxicity mechanisms of silver nitrate in human dermal fibroblasts; Hidalgo E et al.; Certain concentrations of the antiseptic AgNO3, a potent broad-spectrum antimicrobial agent, exert cytotoxic effects on fibroblasts and endothelial cells which are directly related to the wound-healing process . In vitro assessment of human fibroblast cytotoxicity has proved to be a useful method for characterizing cell toxicity mechanisms of topically-applied antiseptics . In the present study human dermal fibroblasts were exposed to AgNO3 at concentrations of 4.12-82.4 microM for 8 and 24 h . Silver ions greatly inhibited fibroblast proliferation and prolonged AgNO3 exposure produced Ag-dependent cell loss . In the sequence of events occurring during our in vitro experimental model, the inhibitory action on DNA synthesis was the primary event in AgNO3 cytotoxicity, associated with significant loss of cell protein . Both parameters decreased as the content of fetal calf serum (FCS) in the exposure medium was gradually reduced from 10 to 2% . The parallel study of DNA synthesis and cell protein content suggests that the toxic damage produced by silver in different phases of the cell cycle may lead to destruction of the entire cell population and therefore hinder the tissue regeneration process . A concentration- and time-dependent depletion of intracellular ATP content is also caused by ionic silver, thereby compromising the cell energy charge which precedes human dermal fibroblast death . Concomitant incorporation of FCS to the medium always attenuated Ag+ cytotoxicity curves in a concentration-dependent fashion and maximum protection was observed at 10% in situations closely resembling physiological conditions. Mayo Clin Proc, 1998 Oct, 73(10), 995 - 1006 General principles of antimicrobial therapy; Thompson RL et al.; Antimicrobial agents are appropriate treatment for acute, severe, persistent, or progressive infectious diseases . The efficacy of treatment depends on the accuracy of the diagnosis of infection and the appropriateness of the antimicrobial agent for the causative microorganism . In this symposium, the antimicrobial agents reviewed correspond with the bacterial, fungal, viral, mycobacterial, parasitic, chlamydial, and other microorganisms that cause disease in humans . Usually, the etiologic possibilities can be limited on the basis of the history and physical examination, laboratory tests, or results of treatment trials . Many of the same findings, however, can result from noninfectious, other inflammatory, or unknown mechanisms . Manifestations such as fever and organ dysfunction are nonspecific and often not caused by an infectious process . Even when infection is clinically apparent, the causative microorganism may not be identified, and empiric treatment with broad-spectrum agents is appropriate in many cases of serious disease. J Am Dent Assoc, 1998 Oct, 129(10), 1455 - 61 Bacteremia and intraoral suture removal: can an antimicrobial rinse help? Brown AR, Papasian CJ, Shultz P, Theisen FC, Shultz RE. Recent studies have shown that bacteremia can result from the removal of intraoral sutures . The authors found that preprocedural use of an antimicrobial oral rinse (0.12 percent chlorhexidine) did not significantly reduce the incidence of bacteremia when compared with no rinse at all . Similarly, a significant relationship between bleeding and bacteremia was not apparent . Most of the positive cultures yielded low colony counts . The results support the rationale for the American Heart Association's 1997 recommendations for use of antibiotic prophylaxis to prevent bacteremia, as well as the importance of good oral hygiene in prevention efforts. J Biol Chem, 1998 Oct 30, 273(44), 28978 - 85 PR-39, a syndecan-inducing antimicrobial peptide, binds and affects p130(Cas); Chan YR et al.; PR-39 is a proline-arginine-rich antimicrobial peptide and an important component of innate immunity . In addition to its antimicrobial effects, PR-39 can alter mammalian cell gene expression and behavior . To determine the mechanism through which PR-39 affects mesenchymal cells, we identify a number of binding targets for PR-39 using a biologically active fragment of PR-39 (PR-39(15)) . We found that PR-39 binds NIH 3T3 in a saturable manner consistent with the existence of a binding target . Similar to full-length PR-39, PR-39(15) interacts with lipid bilayers . After interacting with the membrane, PR-39(15) rapidly enters human microvascular endothelial cells and binds a number of cytoplasmic proteins . PR-39 selectively binds recombinant SH3-containing proteins and was also found to bind a native SH3-containing protein, p130(Cas) . PR-39(15) treatment of endothelial cells results in altered p130 localization . These results show that PR-39(15) binds an SH3-containing signal transduction molecule that has the potential to explain a myriad of effects PR-39 has on mammalian cell behaviors. J Vet Diagn Invest, 1998 Oct, 10(4), 350 - 6 In vitro activity of four antimicrobial agents against North American isolates of porcine Serpulina pilosicoli; Duhamel GE et al.; Porcine colonic spirochetosis is a nonfatal diarrheal disease that affects pigs during the growing and finishing stages of production . The disease is caused by Serpulina pilosicoli, a newly recognized species of pathogenic intestinal spirochete . Antimicrobial therapy aimed at reducing the infection may be helpful in controlling spirochetal diarrhea . In this study, the in vitro antimicrobial susceptibilities of the reference isolate S . pilosicoli P43/6/78 from the United Kingdom and 19 field isolates obtained from pigs in Canada (n = 5) and the United States (n = 14) were determined against the antimicrobial agents carbadox, gentamicin, lincomycin, and tiamulin, all of which are commonly used for control of the related pathogenic intestinal spirochete S . hyodysenteriae . Additionally, the susceptibility or resistance of each isolate against each antimicrobial agent was estimated on the basis of available data on the in vitro antimicrobial susceptibility breakpoints of S . hyodysenteriae . Each isolate was identified on the basis of phenotypic and genotypic markers, and the minimum inhibitory concentration of each antimicrobial agent was determined by the agar-dilution method . All the isolates were susceptible to carbadox and tiamulin . The percentages of isolates susceptible, intermediate, and resistant to lincomycin were 42.1%, 42.1%, and 15.8%, respectively . Slightly less than half of the isolates (47.4%) were susceptible to gentamicin, and the remainder (52.6%) were resistant . Implementation of rational control measures to reduce infection by S . pilosicoli should improve overall health and productivity in swine herds. South Med J, 1998 Oct, 91(10), 957 - 60 Pulmonary gangrene: radiological and pathologic correlation; Curry CA et al.; Although frequently referred to as pulmonary abscess or necrotizing pneumonia, pulmonary gangrene is a distinct entity, requiring prompt medical and often surgical management . Radiographically, it begins as a lobar consolidation, usually in the upper lobes, develops lucencies, and coalesces to form a cavity . A "mass within a mass" or air crescent sign may be present . A vasculitis ensues, devitalizing parenchyma that must be drained surgically or expectorated through a patent bronchus . Serious complications of pulmonary gangrene that often lead to death are detected on computed tomography (CT) before these changes are apparent on chest radiographs . Specifically, a narrowed or obliterated bronchus impedes drainage of necrotic parenchyma and thrombosis of large vessels prevents the delivery of antimicrobial therapy . We review the literature and report this case to show the importance of CT in the early detection and management of pulmonary gangrene. Domest Anim Endocrinol, 1998 Sep, 15(5), 273 - 81 Neuroimmunoregulation and natural immunity; Berczi I et al.; The development and function of the immune system is regulated by neuroendocrine factors . Immune function may be divided into adaptive and natural immunity . Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen . Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system . This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation . Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system . Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope . During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum . This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha . The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes . The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions . Insulin, glucagon, and catecholeamine levels are also raised . Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP) . APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from several hundred to a thousand times within 24-48 hr . Therefore, natural immunity is a polyspecific response to homotopes, which functions as an instantaneous defense mechanism in health and which is rapidly boosted by cytokines and hormones during febrile illness . This is a highly successful defense reaction, as in the overwhelming majority of cases, febrile illness leads to recovery and the development of adaptive immunity in man and higher animals. Biochim Biophys Acta, 1998 Oct 22, 1408(1), 67 - 76 Lumbricin I, a novel proline-rich antimicrobial peptide from the earthworm: purification, cDNA cloning and molecular characterization; Cho JH et al.; A novel antimicrobial peptide was isolated and characterized from the earthworm, Lumbricus rubellus . The antimicrobial peptide was purified to homogeneity by a heparin-affinity column and C18 reverse-phase HPLC, and named lumbricin I . Lumbricin I was a proline-rich antimicrobial peptide of 62 amino acids (15% proline in molar ratio; molecular mass, 7231 Da), whose complete sequence was determined by a combination of peptide sequence and cDNA analysis . The peptide and cDNA sequence analysis revealed that lumbricin I was produced as a precursor form consisting of 76 amino acids, with 14 residues in a presegment and 62 residues in mature lumbricin I . Lumbricin I showed antimicrobial activity in vitro against a broad spectrum of microorganisms without hemolytic activity . In addition, a 29-amino acid peptide, named lumbricin I(6-34), which was derived from residues 6-34 of lumbricin I, showed marginally stronger antimicrobial activity than lumbricin I . Northern blot analysis on total RNA revealed that expression of lumbricin I gene was not induced by bacterial infection, but was constitutively expressed . Furthermore, the expression of lumbricin I gene was specific in adult L . rubellus: Lumbricin I mRNA was detected only in adult L . rubellus, but not in eggs and young L . rubellus. Anal Biochem, 1998 Nov 1, 264(1), 47 - 52 Development of a chemiluminescent urease activity assay for Helicobacter pylori infection diagnosis in gastric mucosa biopsies; Roda A et al.; A chemiluminescent urease activity assay has been developed and optimized using the chemiluminescent pH indicator phthalhydrazidylazoacetylacetone . This compound is stable at pH </= 7 and decomposes at higher pH values, emitting light in the presence of H2O2 . Urease catalyzes hydrolysis of urea to form NH3 and CO2 which increase the pH of the reaction medium, thus allowing the chemiluminescent indicator to decompose and produce photons . The emitted light is proportional to the urease activity when urea is in excess . Urease tests based on colorimetric pH indicators like phenol red are commercially available and commonly used for the rapid diagnosis of Helicobacter pylori infection in gastric mucosa biopsy specimens, since this bacterium produces high amounts of urease . Such colorimetric tests often lack sensitivity, giving false-negative results . The developed chemiluminescent test proved to be at least 50-fold more sensitive than the colorimetric tests, permitting early diagnosis of infection, and it is more rapid, giving results in 1-10 min compared to 30 min . Further applications of this assay could be the in situ localization of urease activity, corresponding to the presence of H . pylori, in gastric mucosa cryosections and the development of high-throughput screening assays of antimicrobial drugs able to inactivate the bacterium . J Pak Med Assoc, 1998 Mar, 48(3), 73 - 7 Prescribing practices: an overview of three teaching hospitals in Pakistan; Najmi MH et al.; The extent and nature of irrational prescribing of drugs has not been explored in Pakistan A pilot study was therefore undertaken in three major teaching hospitals located in the twin cities of Rawalpindi/Islamabad . Six hundred and one prescriptions from medical, paediatrics and psychiatry units of these hospitals were analyzed to study the prescribing pattern . The mean number of drugs per prescription was found to be 2.97 . Only 23.6% drugs were prescribed by their generic names . About 80% of the prescribed drugs were from the National Essential Drug List of Pakistan . Use of injectable preparations was 17.1% . Antimicrobials constituted 20.4% of the drugs prescribed, frequently for cases of acute respiratory infections and gastroenteritis . The average cost of treatment per day was Rupees 26.10 in the outdoors and Rs . 88.36 in indoors . Treatment did not correlate to the diagnosis in 24.6% of the cases . Doses of drugs were inappropriate in 30.6% prescriptions . Duration of treatment was not specified on a vast majority (73.4%) of the prescriptions . The data highlights the need for educational, managerial and regulatory interventions to rationalize the drug use in Pakistan. Nurse Pract Forum, 1998 Sep, 9(3), 170 - 6 Fever of unknown origin; Volker D; Despite substantial advances in antimicrobial therapy, infection remains a major cause of morbidity and mortality in immunocompromised cancer patients . As more intensive, curative antineoplastic treatment regimens are established, the risk for fatal infectious complications will continue to rise . Signs and symptoms of infection in this compromised population may be subtle; yet, an undetected and untreated infection can quickly evolve into septic shock and death . Typically, fever is considered to be a clinical hallmark of infection . Yet, most patients initially present to the clinical setting with a fever of unknown origin . Given the lethal nature of infections in immunocompromised patients, one must assume that the febrile patient is infected until proven otherwise. Schweiz Rundsch Med Prax, 1998 Sep 2, 87(36), 1120 - 5 {Antibiotic therapy in leukopenia}; Bohme A et al.; Intensified chemotherapy-induced long-term neutropenia is the main cause for morbidity and mortality of patients with hematologic malignancies . The successful management of neutropenia is based on hygienic procedures antimicrobial prophylaxis and therapy, and diagnostics . Until today, Co-Trimoxazole or fluoroquinolenes and oral amphotericine B are the prophylactic standard . The initial therapy of febrile neutropenia has to be started empirically before identification of causative pathogens or infectious foci . The febrile episodes should be treated with broad spectrum antibiotics (combinations or monotherapy) due to the spectrum of microorganisms or resistance situation at hospital . In case of non-response after 3-4 days the initial therapy should be modified, in addition to further antibacterial therapy the start with an antifungal drug has to be recommended . In patients with pulmonary infiltrates the early treatment with amphotericine B has been shown to be more advantageous than delayed antifungal therapy . Furthermore, the antibiotic therapy is based on proven microorganisms, susceptibility testing and infectious foci . The value of interventional treatment with G-CSF or GM-CSF is controversely discussed . An uncompromising handling of febrile neutropenia is necessary to reduce the mortality due to infections in patients with hematologic malignancies. Biol Pharm Bull, 1998 Sep, 21(9), 919 - 23 Pharmacological properties of T-3762, a novel fluoroquinolone antimicrobial agent in parenteral use . III . Chemical structures and dermovascular permeability-increasing activities; Furuhata K et al.; Fluoroquinolone antibiotics and chemically related compounds including the pazufloxacin methanesulfonate named T-3762 were examined for their ability to increase cutaneous vascular permeability following intradermal injection in dogs . A positive skin reaction was produced by the injection of a compound with a substituent of the piperazinyl, 4-piperizyl, 3-aminopyrolizinyl or 3-aminocyclobutyl group at the 7-position (C-7) of the quinolone skeleton at a minimum concentration of 101.8 microg/ml or less . Substitution at position 1, 6 or 8 of the ring nucleus hardly affected the activity of the compounds with the C-7 substituted piperazinyl group . The compounds with 7-positioned substituents other than the piperazinyl group showed relatively weak activity, and in particular those with the 1-aminocyclopropyl group including T-3762 were barely positive in concentrations of more than 500 microg/ml . An analysis of the three-dimensional models of the compounds with the C-7 substituted, nitrogen-containing groups revealed that the range of the geometrically optimum distance between the nitrogen and the carbon atoms was from 2.98 to 4.98 A for highly active compounds and from 2.47 to 2.65 A for weakly active compounds . In conclusion, the C-7 substituted piperazine moiety of the molecules of already-known fluoroquinolone antibiotics may be responsible for the ability to increase cutaneous vascular permeability, whereas T-3762 is practically inactive because the free amino nitrogen of the 1-aminocyclopropyl group is conformationally present at a shorter distance from the carbon atom at position 7 of the ring nucleus. Adv Exp Med Biol, 1998, 443, 267 - 71 Lactoferrin and interleukin-6 interaction in amniotic infection; Otsuki K et al.; Lactoferrin (Lf) has been found in most biological fluids including amniotic fluid and cervical mucoids in pregnant women, and released from neutrophils in response to the inflammation . As Lf possesses antimicrobial properties, it is widely considered to be an important component of the host defence against microbial infections . It is known that premature labor is caused by amniotic infection with the increase of prostaglandin production . High concentration of the inflammatory cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) in the amniotic fluid has been known . However, changes of Lf in amniotic fluid with infection has not been reported . In the present study, Lf concentrations in amniotic fluid were measured under the intra-uterine infections state and the biological significance of Lf was investigated . The effects of Lf on the IL-6 and IL-6mRNA production in cultured amnion cells were also investigated . The concentrations of Lf and IL-6 in amniotic fluid with CAM were 8.76 +/- 0.65 micrograms/ml and 6.92 +/- 4.88 ng/ml (n = 28) respectively and both were significantly higher (p < 0.01) than those without CAM {0.86 +/- 0.81 microgram/ml and 0.34 +/- 0.25 ng/ml (n = 31)} . Significant positive correlation (r = 0.91, p < 0.01) between Lf and IL-6 levels in amniotic fluid was found . IL-6 production induced by lipopolysaccharide (LPS) (100 ng/ml) in cultured amnion cells was significantly inhibited (p < 0.05) under the physiological concentration of Lf in amnion . Total RNA was extracted from the amniotic cells by guianizine solution . RT-PCR procedure and product analysis were performed from one microgram aliquote of total RNA . beta-actin was used as an international standard and c-DNA samples were followed by 30 cycles of PCR . RT-PCR product of IL-6 mRNA was detected by Southern hybridization . Expression of IL-6 mRNA was inhibited by the addition of Lf . From the results, the possibility that Lf might suppress amniotic IL-6 production under the condition of amniotic infection is suggested . It is also suggested that Lf might act as self defence mechanism from intra-uterine infection. Adv Exp Med Biol, 1998, 443, 215 - 20 A helical region on human lactoferrin . Its role in antibacterial pathogenesis; Chapple DS et al.; Human lactoferrin contains a 47 amino acid peptide, named lactoferricin H, which is thought to be responsible for its antimicrobial activity . Lactoferricin includes a loop region, which resides on the outer surface of the N-lobe of lactoferrin, adopting an alpha helix with a hydrophobic tail . Peptides have been synthesised corresponding to the highly charged alpha helix (HLP 2) and hydrophobic tail region (HLP 5) . HLP 2 has potent antibacterial activity whereas HLP 5 had no activity . To investigate the relationship between structure and function of HLP 2, HLP 6 was synthesised with a proline replacing methionine . This substitution was predicted to disrupt the helical region of the peptide and the orientation of the positively charged residues . Antibacterial activity was significantly reduced when tested against Escherichia coli serotype 0111, NCTC 8007 . The mode of action of HLP 2 against the bacterial membrane was investigated by flow cytometric analysis, using Escherichia coli, NCTC 8007 . Membrane potential and integrity were monitored using the fluorescent probes, bis 1,3-(dibutylbarbituric acid) trimethine oxonol and propidium iodide respectively . HLP 2 caused complete loss of membrane potential and integrity, with irreversible damage to the cell as shown by rapid loss of viability . We conclude that HLP 2 causes membrane disruption and that helicity is an important factor for antibacterial activity. Adv Exp Med Biol, 1998, 443, 57 - 63 Glycation ligand binding motif in lactoferrin . Implications in diabetic infection; Li YM; Lactoferrin and lysozyme are two important, naturally occurring antibacterial proteins found in saliva, nasal secretions, milk, mucus, serum and in the lysosomes of neutrophils and macrophages . Both proteins bind specifically to glucose-modified proteins bearing advanced glycation endproducts (AGEs) . Exposure to AGE-modified proteins blocks the bacterial agglutination and bacterial killing activities of lactoferrin and also inhibits the bactericidal and enzymatic activity of lysozyme . Peptide mapping by AGE ligand blot revealed two AGE-binding domains in lactoferrin, and a single AGE-binding domain in lysozyme . None of these AGE-binding domains displayed any significant homology in their primary sequences; however, a common 17-18 amino acid cysteine loop motif (CX15-16C) was identified among them, which we named an ABCD motif (AGE-Binding Cysteine-bounded Domain) . Similar domains are also present in other antimicrobial proteins such as defesins . Hydrophilicity analysis indicated that each of these ABCD loops is markedly hydrophilic . Synthetic peptides, corresponding to these motifs in lactoferrin and lysozyme, exhibited AGE-binding activity . Since diabetes is associated with abnormally high levels of tissue and serum AGEs, the elevated AGEs may inhibit endogenous antibacterial proteins by binding to the conserved ABCD motif, thereby increasing susceptibility to bacterial infections in diabetic individuals . These results may provide a basis for the development of new approaches to prevent diabetic infections. Adv Exp Med Biol, 1998, 439, 55 - 66 Prospects for the metabolic engineering of bioactive flavonoids and related phenylpropanoid compounds; Dixon RA et al.; The successful engineering of complex metabolic pathways will require, in addition to availability of cloned genes and promoters, knowledge of the regulatory mechanisms that control metabolic flux into the pathway including post-translational phenomena such as metabolite channeling . We are interested in modifying pathways for the synthesis of isoflavonoids and other bioactive phenylpropanoid compounds in transgenic plants . We describe studies on flux control utilizing transgenic tobacco plants that under- and over-express key biosynthetic enzymes, and outline experimental approaches for the molecular dissection of potential metabolic channels in the synthesis of antimicrobial flavonoid derivatives in alfalfa and other species. Infect Dis Clin North Am, 1998 Sep, 12(3), 689 - 99, ix Value of noninvasive studies in community-acquired pneumonia; Plouffe JF et al.; Noninvasive diagnostic studies, i.e., sputum gram stain, sputum culture, blood culture and antigen detection assays will assist the clinician in the selection of initial antimicrobial therapy in some patients . These tests may be even more valuable in adjusting treatment regimens to prevent the use of broad spectrum antimicrobial agents as routine therapy. Ther Drug Monit, 1998 Oct, 20(5), 464 - 8 Assays for therapeutic monitoring and pharmacokinetic investigations of aminoglycosides: quality aspects; White LO; Clinical laboratory investigations used to aid antimicrobial chemotherapy of serious infection include routine sensitivity testing and, in the case of those drugs with a narrow therapeutic range, routine assays for therapeutic monitoring to assist with dosage individualization . Tests must be of a sufficiently high quality to be clinically useful . Laboratories ensure quality through standard operating procedures, internal quality control procedures, and participation in external quality assessment (EQA) programs . This article demonstrates how EQA returns to the United Kingdom National External Quality Assessment Scheme for Antibiotic Assays and the activity of the United Kingdom National Quality Assurance Advisory Panel showed marked improvement in the technical quality of assays as exemplified by gentamicin assays . The article also highlights additional quality concerns not subject to EQA. Infect Dis Clin North Am, 1998 Sep, 12(3), 671 - 88 Airway infection; Niroumand M et al.; Bronchitis in its acute and chronic forms with recurrent acute exacerbations is one of the most common reasons for physician visits, accounting for a significant cost to the health-care system, lost work days, and increased morbidity and mortality . Smoking and recurrent lower respiratory tract infections are major risk factors for chronic bronchitis . Therefore, smoking cessation and vaccination strategies are cornerstones of management in terms of halting disease progression and reducing the frequency of infectious exacerbations . Bacterial infection is the main culprit in acute flares of the disease . Routine antimicrobial therapy fails in a significant number of patients, and therapeutic failures lead to increased costs . Several stratification schemes have been proposed to improve initial antimicrobial selection . These schemes identify patient's age, severity of underlying pulmonary dysfunction, frequency of exacerbations, and the presence of comorbid illnesses as predictors for likely pathogens and to guide antimicrobial selection . This approach may reduce the risk for treatment failure, which would have significant medical and economic implications . Improved understanding of the roles of airway inflammation and infection in the pathogenesis of progressive airway disease, in addition to future studies examining the efficacy of newer classes of antimicrobials, should guide physicians to target early and effective treatment to high-risk patients. Infect Dis Clin North Am, 1998 Sep, 12(3), 631 - 46, viii Intrapulmonary concentrations of antimicrobial agents; Nix DE; The delivery of antimicrobial agents to the site of infection has always been considered important . Lung infections are typically localized to the bronchial mucosa, endothelial lining fluid, and/or alveolar macrophages . Significant advances have been made in measuring antimicrobial concentrations at these sites, although some of the methods need further refinement and standardization . Relating various intrapulmonary site concentrations to efficacy or treatment failure requires further study . This article reviews the theory and methods relating to the measurement of intrapulmonary delivery of antimicrobial agents, and compares the intrapulmonary delivery of agents commonly used for the treatment of lower respiratory infections. Clin Perinatol, 1998 Sep, 25(3), 699 - 710 Rationale and potential use of cytokines in the prevention and treatment of neonatal sepsis; Goldman S et al.; Despite advances in the use of newer antimicrobials and aggressive supportive care, sepsis and its sequalae remain a major source of morbidity and mortality in the neonate . The VLBW neonate is especially at high risk . We and others have demonstrated that neonatal MNC are deficient in their production of G-CSF and GM-CSF, which, in part, may explain the neonates propensity to develop neutropenia during times of sepsis . G-CSF and GM-CSF have been shown to both enhance neonatal neutrophil superoxide production in vitro and to increase circulating neutrophil numbers through expansion of the NSP in the BM in neonatal rats and humans . G-CSF is protective (if given with or before antibiotics) during experimental GBS in the neonatal rat and appears to be well tolerated (both short term and 2 years after its use) in the human neonate . In a phase II randomized pilot multicenter study, GM-CSF prophylaxis in the VLBW neonate was well tolerated during 4 weeks of administration and was noted to have significantly reduced the incidence of nosocomial infections . Future efficacy and safety studies in more neonates need to be completed and assessed before the routine pharmacologic use of G-CSF or GM-CSF is recommended to prevent and treat neonatal sepsis. Int Dent J, 1998 Jun, 48(3 Suppl 1), 305 - 15 Chemical treatment of periodontitis: local delivery of antimicrobials; Killoy WJ; Periodontitis is a bacterial infection . It appears in a generalised form but more often appears in local areas in a patient's mouth or is reduced to localised areas by mechanical treatment . Periodontitis lends itself well to treatment by means of a controlled local delivery system using an antimicrobial agent . Several products have been introduced or are in the process of clearing regulatory agencies . It is the goal of all local delivery systems to deliver high concentrations of an antimicrobial directly to the site of the periodontal infection . Concentrations of medication can be achieved considerably higher than could be obtained with systemic administration, while the systemic uptake of the medication is minimal . Five local delivery systems (tetracycline fibre, doxycycline polymer, chlorhexidine chip, minocycline ointment and metronidazole gel) are now available . Techniques for their use and the supporting scientific evidence are presented and indications for the use of the various systems are also discussed . These local delivery systems offer the clinician additional therapeutic procedures to aid in the treatment of the chronic inflammatory periodontal diseases. Int Dent J, 1998 Jun, 48(3 Suppl 1), 290 - 7 Modern supragingival plaque control; Iacono VJ et al.; Supragingival plaque control is essential for the maintenance of oral health . Despite the many chemotherapeutic agents available as mouthrinses and toothpastes, mechanical plaque removal is still the best method to achieve effective plaque control . This is due, in part, to the lack of development of oral antimicrobials with the effectiveness and substantivity of chlorhexidine gluconate but without its adverse effects of dental staining and calculus formation . The use of the numerous mechanical (manual and electric) oral hygiene devices extant and their effectiveness, however, are dependent upon patient dexterity and compliance and concomitant active professional treatment for the monitoring of home care, oral hygiene instruction and patient motivation . This paper evaluates the current methods available to reduce plaque and gingivitis with emphasis on their effectiveness at both supragingival plaque control and disease prevention . In addition, recent studies on the newer oscillating/rotating electric plaque removers and interdental cleaning devices will be discussed as related to their efficacy and compliance. Arch Intern Med, 1998 Oct 12, 158(18), 1993 - 2000 Antimicrobial photosensitive reactions; Vassileva SG et al.; Photosensitivity reactions are recognized as unwanted adverse effects of an array of commonly administered topical or systemic medications, including nonsteroidal antiinflammatory agents, antifungals, and antimicrobials . When a drug induces photosensitivity, exogenous molecules in the skin absorb normally harmless doses of visible and UV light, leading to an acute inflammatory response . In phototoxic reactions, the damage to tissues is direct; in photoallergic reactions, it is immunologically mediated . In vitro and in vivo assay systems can assist in predicting or confirming drug photosensitivity . The incidence of photosensitivity reactions may be too low to be detected in clinical studies and may become recognized only in the postmarketing stage of drug development . Some drugs have been withdrawn because of photosensitivity effects that appeared after general release . Photosensitivity reactions have been studied for a number of topical antimicrobials and for the sulfonamides, griseofulvin, the tetracyclines, and the quinolones . Incidence and intensity of drug phototoxicity can vary widely among the different compounds of a given class of antimicrobials . When phototoxic effects are relatively low in incidence, mild, reversible, and clinically manageable, the benefits of an antimicrobial drug may well outweigh the potential for adverse photosensitivity effects. Infect Control Hosp Epidemiol, 1998 Sep, 19(9), 653 - 6 Use of amoxicillin-clavulanate and resistance in Escherichia coli over a 4-year period; Natsch S et al.; OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coli were detected . DESIGN: Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns . SETTING: A 260-bed acute-care hospital in Switzerland . INTERVENTIONS: Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate . The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely . RESULTS: The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995 . The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995 . The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995 . No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period . CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E coli to it . It was not possible to prove a causative relationship . Only a temporal association was discovered . The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments. Lancet, 1998 Oct 10, 352(9135), 1207 - 12 Escherichia coli O157:H7; Mead PS et al.; Escherichia coli O157 was first identified as a human pathogen in 1982 . One of several Shiga toxin-producing serotypes known to cause human illness, the organism probably evolved through horizontal acquisition of genes for Shiga toxins and other virulence factors . E . coli O157 is found regularly in the faeces of healthy cattle, and is transmitted to humans through contaminated food, water, and direct contact with infected people or animals . Human infection is associated with a wide range of clinical illness, including asymptomatic shedding, non-bloody diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome, and death . Since laboratory practices vary, physicians need to know whether laboratories in their area routinely test for E . coli O157 in stool specimens . Treatment with antimicrobial agents remains controversial: some studies suggest that treatment may precipitate haemolytic uraemic syndrome, and other studies suggest no effect or even a protective effect . Physicians can help to prevent E . coli O157 infections by counselling patients about the hazards of consuming undercooked ground meat or unpasteurised milk products and juices, and about the importance of handwashing to prevent the spread of diarrhoeal illness, and by informing public-health authorities when they see unusual numbers of cases of bloody diarrhoea or haemolytic uraemic syndrome. J Hosp Infect, 1998 Sep, 40(1), 47 - 53 Quality of perioperative antibiotic administration by French anaesthetists; Martin C et al.; Antibiotics are the most prescribed drugs in hospitals in France and approximately one-third of prescriptions are for antimicrobial prophylaxis . Although the principles of prophylaxis have been defined over the years, there is still widespread misuse of antimicrobials for that purpose . The aim of this survey was to determine whether prescription of prophylactic antibiotics by French anaesthetists complies with the French Guidelines on Surgical Antibiotic Prophylaxis . Information was sought concerning the agent(s) recommended, the timing of the first dose and the duration of prescription . A total of 1473 French anaesthetists was studied . For the great majority (93%), the first antibiotic dose is administered at time of induction of anaesthesia, as recommended by the guidelines . First- and second-generation cephalosporins are frequently selected, as well as co-amoxiclav . In contrast to the guidelines, third-generation cephalosporins (3GCs) are widely prescribed in digestive and urological surgery and quinolones in urological surgery . Duration of prescription is limited to 48 h by most anaesthetists (94%), however there is a strong tendency to prescribe prophylaxis for longer periods in the immunocompromised and patients undergoing major surgery . This survey indicates discrepancies between the French Guidelines on Surgical Antibiotic Prophylaxis and the current practice of French anaesthetists . Major concerns are the use of antibiotics such as 3GCs or fluoroquinolones and prescription for periods exceeding 48 h . In conclusion, compliance with guidelines for prophylactic antimicrobial administration should be more strict in surgical patients. J Hosp Infect, 1998 Sep, 40(1), 39 - 46 Analysis and impact of infectious disease consultations in a general hospital; Schlesinger Y et al.; During an 18-month period, data from all patients in whose care our infectious diseases (ID) service was involved, were recorded in a computerized database . A total of 4184 new consultations was recorded . The consultations were solicited by the patients' physicians in 3326 cases (80%) and initiated by the ID service in the remainder . The purpose of the consultations was diagnosis (14%), therapy (39%), both diagnosis and therapy (40%), and prophylaxis (6%) . Two thousand and ninety-four consultations (50%) were performed at the bedside, and the others by personal or telephone discussion . ID consultation was given in more than 10% of admitted patients in six departments, 46% of the admissions in the ICU, and 6.9/100 hospitalized patients . Recommendations included: antibiotic manipulation (i.e., initiation, change or discontinuation of antibiotic treatment) (51%); performance of tests (13%); performance of diagnostic or therapeutic procedures (5%); prophylaxis (4%) or no change in management (26%) . Analysis of the solicited vs unsolicited consultations and of the bedside vs telephone consultations revealed that sub-groups of consultations differ significantly from each other in many aspects . Recording of consultations enables the ID service to evaluate its activity and to direct efforts to departments with high rates of infectious diseases and/or antimicrobial usage. Med Mycol, 1998 Aug, 36(4), 205 - 12 Characterization of a single group I intron in the 18S rRNA gene of the pathogenic fungus Histoplasma capsulatum; Lasker BA et al.; A 425-bp insertion in Histoplasma capsulatum strain G186B, denoted as Hc.SSU.1, was identified as a group I intron, based on the presence of the conserved sequence elements P, Q, R and S and a predicted secondary structure consistent for group I introns . The Hc . SSU.1 sequence from strain G186B was identical to strain G184B but differed from strain FLs1 by five nucleotides . Hc.SSU.1 was most similar to the group I intron from the black mould Exophiala castellanii . Southern blot analysis suggests that the intron is not dispersed in the genome and that most, if not all 18S rRNA genes harbour the intron . Northern blots demonstrated absence of the intron from mature 18S rRNA . A Hc.SSU.1-specific PCR assay detected the intron in six of 37 isolates of Histoplasma . Hc.SSU.1-containing strains exhibited no significant differences in antimicrobial susceptibilities when compared to isolates not containing Hc.SSU.1 . This investigation demonstrates the existence of group I intron sequences in the H . capsulatum genome and its evolutionary relationship among other group I intron sequences. Med Mycol, 1998 Jun, 36(3), 135 - 41 Antimicrobial activity of AmBisome and non-liposomal amphotericin B following uptake of Candida glabrata by murine epidermal Langerhans cells; Sperry PJ et al.; The antifungal efficacy and cellular toxicity of AmBisome(R) and non-liposomal amphotericin B were compared in cultured epidermal Langerhans cells infected with Candida glabrata . Uptake of the yeast was determined by light and electron microscopy, and viability was assessed by plating dilutions of lysates from yeast-infected Langerhans cells and counting colony forming units . The Candida-infected Langerhans cells were incubated for 6, 24 or 48 h with 12.5 micro ml-1 of AmBisome or non-liposomal amphotericin B, non-drug-containing liposomes or media . Intracellular C . glabrata incubated with media or non-drug-containing liposomes showed a 2 log increase in cfu, and microscopic examination revealed budding yeast within the Langerhans cells . Both liposomal and non-liposomal amphotericin B treatment reduced intracellular growth of C . glabrata by 5 logs over 48 h of incubation . A morphometric analysis of cell ultrastructure demonstrated that AmBisome-treated Langerhans cells retained their cell architecture, but Langerhans cells treated with non-liposomal amphotericin B were characterized by the absence of intact organelles, disrupted non-granular cytoplasm and the presence of many large vacuoles . In conclusion, AmBisome was significantly less toxic for epidermal Langerhans cells than amphotericin B, but demonstrated comparable antifungal efficacy . After 48 h of drug exposure, both forms of amphotericin B effectively inhibited intracellular growth of C . glabrata, but only AmBisome did not damage the Langerhans cells. J Nucl Med, 1998 Oct, 39(10), 1778 - 83 Bone scintigraphy in the detection of chronic recurrent multifocal osteomyelitis; Mandell GA et al.; In this study, we describe the importance of the whole-body bone scan in diagnosing the multifocality of chronic recurrent multifocal osteomyelitis (CRMO) and in distinguishing it from unifocal acute hematogenous osteomyelitis . MATERIALS: The medical records and two-phase, whole-body bone scans of 14 patients (mean age 10.5 yr) with the diagnosis of CRMO, were retrospectively reviewed . The diagnosis of CRMO was based on bone biopsy in 9 patients and clinical course/laboratory findings in 5 . Bone scans were evaluated for geographic and anatomic locations of their lesions . Correlative radiographs of areas of abnormal uptake were performed to assess the radiographic appearance of the lesions . RESULTS: The presentation of the disease was localized to one painful, tender and swollen periarticular site 86% of the time . The number of lesions detected by bone scan varied from 1-18 (mean 6) . Most lesions were metaphyseal, proximal or distal tibial lesions . Purely sclerotic or mixed (sclerosis and lysis) lesions were found on radiographs . Bilateral lesions were seen in 64% of patients . Biopsies were negative for organisms in all patients and exhibited subacute or chronic histologic changes in most instances . Complications of chronic hyperemia included marked overgrowth (5), diffuse demineralization (1), angular deformity (1) and length discrepancy (1) . CONCLUSION: The identification of the multifocal configuration of the disease process by two-phase (soft-tissue and delayed) whole-body bone scintigraphy results in appropriate diagnosis and therapy of CRMO . Additional sites for possible bone biopsy become apparent for exclusion of other diagnoses . Supportive (nonsteroidal, anti-inflammatory medication) instead of antimicrobial therapy can be initiated with significant cost savings. Pharmacol Res, 1998 Oct, 38(4), 275 - 8 Effects of cardio-pulmonary bypass on vancomycin plasma concentration decay; Miglioli PA et al.; The objective of the study was to investigate possible changes in vancomycin serum levels induced by cardio-pulmonary bypass (CPB) . Ten cardiac patients (seven males, three females, aged between 56 and 81), who underwent cardiac surgery requiring CPB, took part in the study . Vancomycin (15 mg kg-1) was intravenously infused over 60 min before anaesthesia and blood samples were taken at appropriate times after drug administration (0, 0.5, 1, 6, 8 h), after starting CPB (0, 5, 30 and 60 min) and after aortic unclamping (0, 5, 30, 60, 120 min) . Drug serum concentrations were determined by means of a fluorescence polarization immunoassay . The area under the concentration-time curve (AUC) measured during CPB were compared with the AUC extrapolated in the same interval by fitting a two-compartment pharmacokinetic model to drug concentrations obtained before and after CPB . Five minutes after starting CPB vancomycin serum levels decreased, on average, by 40.9% and remained steadily lower than the expected values over the next 60 min . In the same interval, the measured AUC was 31.7% lower than the expected AUC . In no instance did serum levels fall below the MIC for most common pathogens (1-2 mg l-1) . At aortic unclamping serum levels slightly rebounded but tended to remain lower than the expected concentrations over the next 120 min . In conclusion, during CPB vancomycin serum levels invariably decreased but, at the dose employed (15 mg kg-1), remained in a potentially effective range for antimicrobial prophylaxis . Am J Kidney Dis, 1998 Oct, 32(4), 642 - 5 Ofloxacin clearance during hemodialysis: a comparison of polysulfone and cellulose acetate hemodialyzers; Thalhammer F et al.; The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage renal disease during hemodialysis using two different dialyzers: a polysulfone membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T) . All patients received 100 mg ofloxacin orally per day before dialysis . The hemodialysis clearance per square meter surface area was significantly different, with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively . The serum concentration was reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area and 45.5%+/-4.8% per square meter surface area . The half-life was 4.2+/-1.8 hours and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and 23.3+/-1.7 hours between the dialysis sessions, respectively . Comparing polysulfone and cellulose acetate dialyzers, the material of the membrane influences the half-life, the dialysis clearance, and the percentage of drug extracted during hemodialysis . We conclude that the type of dialyzer used has to be taken into account in dosage recommendations for antimicrobial therapy in hemodialysis patients. Pediatr Res, 1998 Oct, 44(4), 499 - 506 Milk fat globule glycoproteins in human milk and in gastric aspirates of mother's milk-fed preterm infants; Peterson JA et al.; Human milk fat globule (HMFG) glycoproteins can prevent infections by microorganisms in breast-fed infants; the MUC-1 mucin inhibits binding of S-fimbriated Escherichia coli to buccal mucosa, and lactadherin may prevent symptomatic rotavirus infections . In this study, the survival of these HMFG glycoproteins in the stomach of human milk-fed preterm infants (gestational age = 27.5 +/- 0.4 wk) was assessed, and levels in their mothers' milk determined, using specific RIAs . Butyrophilin, a major component of HMFG membrane that has no demonstrated antimicrobial activity, was studied for comparison . The levels of mucin, lactadherin, and butyrophilin in 41 milk samples of 20 mothers were 729 +/- 75, 93 +/- 10, and 41 +/- 3 microg/mL, respectively . Mucin and lactadherin were significantly higher in early milk samples (<15 d postpartum) than in later milk samples (15-90 d postpartum), whereas butyrophilin showed no such difference . Significant amounts of mucin and lactadherin were found in almost all gastric aspirates of human milk-fed infants, even 4 h after feeding (mucin, 270 +/- 30 microg/mL; lactadherin, 23.2 +/- 4.4 microg/mL), whereas butyrophilin was rapidly degraded in the majority of aspirates . Western blot analysis demonstrated that the immunoreactive mucin, lactadherin, and butyrophilin in the milk-fed gastric aspirates had the expected native molecular weights . Mucin and lactadherin survived at all gastric pH values, whereas butyrophilin was found only at pH > 4 . Neither lactadherin nor butyrophilin were detected in gastric aspirates of formula-fed infants (gestational age = 27.8 +/- 0.5 wk), whereas the very low level of mucin (9.1 +/- 1.1 microg/mL) in this group is presumably cross-reacting gastric mucin . These results demonstrate that two HMFG glycoproteins implicated in prevention of infection, MUC-1 mucin and lactadherin, survive and maintain their integrity in the stomachs of human milk-fed preterm infants. Support Care Cancer, 1998 Sep, 6(5), 457 - 61 Stratification in clinical trials of febrile neutropenia; Elting LS; Patients with febrile neutropenia are characterized by well described prognostic factors leading to heterogeneity of risk of serious clinical outcomes . These prognostic factors complicate the design and interpretation of clinical trials of antimicrobial therapy in this population . Stratification is a method by which comparability of groups is ensured . This method can be employed prior to randomization or during the analysis . Factors that should be considered for stratification prior to randomization include the underlying neoplasm (leukemia vs solid tumor vs BMT), use of granulocyte growth factors, comorbid conditions and study site (in multicenter trials) . In stratified analyses, trend in neutrophil count, site of infection, organism and susceptibility should be considered. Support Care Cancer, 1998 Sep, 6(5), 444 - 8 Criteria for response in patients in clinical trials of empiric antibiotic regimens for febrile neutropenia . Is there agreement? Feld R. A review of the literature on the criteria of response in patients on clinical trials of empiric antibiotic therapy revealed that there are at least three definitions utilized worldwide along with individual investigator definitions . The main definitions include definitions by Pizzo from the NCI, by the EORTC Antimicrobial group and by the Immunocompromised Host Society . The outcome in clinical trials can be affected by the definition used if the major endpoint in the study compares response rates of two or more initial empiric antimicrobial regimens for febrile neutropenia . Survival based definitions (Pizzo) are very useful but may not identify which regimen required the least number of modifications during the critical initial 3-5 days of trial . Evaluations later in the course of the febrile episode will not likely be influenced by these definitions as most patients with prolonged and severe neutropenia will eventually require modifications of therapy . A consensus to use a single response definition is necessary to allow comparisons and meta-analysis of results with specific antibiotic regimens for febrile neutropenia . These must be enforced by editors of major medical journals to truly allow this to happen. Semin Liver Dis, 1998, 18(3), 295 - 307 Current concepts in pediatric liver transplant; Alonso MH et al.; Orthotopic liver transplantation has significantly improved the survival rate of children with end-stage liver disease . Efforts to correct abnormalities existing prior to transplantation coupled with improved surgical techniques and immunosuppression have led to better quality of life and 1-year survival rates approaching 90% in many centers . Despite this success the expanding waiting list population of all ages has driven development of operative techniques to expand the donor pool . Building on the success of reduced-size transplantation, split-liver and living-donor transplantation are now suitable alternatives, especially when used in candidates with satisfactory clinical stability . In the post-operative period, infectious complications represent an important cause of morbidity and mortality . Although antimicrobial regimens are effective in the immediate post-operative phase, acquisition of viral infections represents a major concern particularly in the young liver recipient . Early detection and development of new anti-viral agents are likely to decrease occurrence of post-transplant proliferative disorders and optimize longterm transplantation outcome. J AOAC Int, 1998 Sep-Oct, 81(5), 978 - 90 Delvotest SP for detection of cloxacillin and sulfamethoxazole in milk: IDF interlaboratory study . International Federation Dairy; Suhren G et al.; Under the auspices of the International Dairy Federation's Group E503, a collaborative study of the Delvotest SP multiplate microbial inhibitor test was performed to gain information about the detection limits of 2 antimicrobial agents (a beta-lactam and a sulfa compound), the variation of test results between users and 2 batches of the test, and the reasons for deviating results . Lyophilized milk samples spiked with various concentrations of cloxacillin or sulfamethoxazole were analyzed . Each substance/concentration combination was tested with each of 2 test batches 14 or 15 times per participating laboratory . Test results were to be read by more than one person and reported on separate forms . Results were obtained from 29 laboratories, which included 5 with no experience and 11 with limited experience with this test . Detection limits for cloxacillin (22.5 or 30 micrograms/kg, depending on batch) and sulfamethoxazole (45 micrograms/kg) were established from dose-response curves . A small difference in cloxacillin detection levels between the 2 test batches was observed . Analyses of samples gave almost unanimous results (> or = 95%) . Of deviating results, defined as anomalous results (1.4% of readings), half could be attributed to human errors and half to procedural errors. Anesteziol Reanimatol, 1998 Jul-Aug, (4), 27 - 9 {Specific antimicrobial immunity in patients with suppurative soft-tissue diseases undergoing conventional and modified ultraviolet irradiation of autologous blood}; Ostrovskii VK et al.; Study of titers of specific antibacterial antibodies in the plasma by passive hemagglutination test and of the number of antibody-producing cells (APC) by local hemolysis test in patients with purulent diseases of soft tissues showed that both values increased after UV exposure of autoblood . This increase was more expressed after differentiated exposure of erythrocytic and leukocytic mass than after common UV exposure, which is explained by more complete exposure of leukocytes participating in immunological reactions . Study of APC during a UV session showed an increase in the count of these cells 6-8 h after exposure. FEMS Microbiol Lett, 1998 Sep 15, 166(2), 305 - 9 Overexpression of marA, soxS, or acrAB produces resistance to triclosan in laboratory and clinical strains of Escherichia coli; McMurry LM et al.; Triclosan (Irgasan) is a broad spectrum antimicrobial agent used in handsoaps, toothpastes, fabrics, and plastics . It inhibits lipid biosynthesis in Escherichia coli, probably by action upon enoyl reductase (FabI) (McMurry, L.M., Oethinger, M . and Levy, S.B . (1988) Nature 394, 531-532) . We report here that overexpression of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding positive regulators of acrAB, decreased susceptibility to triclosan 2-fold . Deletion of the acrAB locus increased the susceptibility to triclosan approximately 10-fold . Four of five clinical E . coli strains which overexpressed marA or soxS also showed enhanced triclosan resistance . The acrAB locus was involved in the effects of triclosan upon both cell growth rate and cell lysis. Clin Infect Dis, 1998 Sep, 27(3), 619 - 26 Intramedullary abscess of the spinal cord in the antibiotic era: clinical features, microbial etiologies, trends in pathogenesis, and outcomes; Chan CT et al.; We review the clinical features, microbial etiologies, mechanisms of infection, and outcomes of 25 cases of intramedullary abscess of the spinal cord (IASC) reported between 1977 and 1997, the modern era . All patients presented with motor and/or sensory neurological deficits . Back pain and/or radicular pain was common (60%); fever was present in a minority (40%) of patients . Preexisting abnormalities of the spinal cord and/or vertebral column were present in 44% of cases . Contiguous spread of infection through a congenital dermal sinus was the mechanism of infection in 24% of cases . The infection was fatal in 8% of cases; persistent neurological deficits were documented in 70% of patients who survived . To assess the impact of antimicrobial therapy on the pathogenesis and outcomes of IASC, cases reported in the modern era are compared with 42 cases of IASC reported between 1830 and 1944, the preantibiotic era. Ann Pharm Fr, 1998, 56(4), 184 - 6 {The antimicrobial properties of some chewing sticks from Togo}; Kpakote KG et al.; Eight togolese species for chewing sticks are tested on germs . Most of them have antimicrobial properties. Ann Pharm Fr, 1998, 56(4), 181 - 3 {Antimicrobial activity of some derivatives of pyrimidine}; Mangalagiu I et al.; In this paper the authors present the antimicrobial and antifungical tests of some new 3-methylpyrimidine compounds . The test was performed using the diffusimetric method with rustlessteel cylinders based on the diffusion of the tested substances on the gelose surface . The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and biological activity in the pyrimidine series: 1 . The pyrimidinium ylides are less active comparatively with the corresponding salts . That means that the zwitter ionic structure did not favour the activity . 2 . Comparative with the corresponding pyridazine(1,2-diazine) derivatives, the pyrimidine(1,3-diazine) compounds are more active . The increase of activity of the pyrimidine compounds could be attributed of the influence of the pyrimidine ring . 3 . The most active pyrimidine compound which is tested is that one in which radical R is an amide group . 4 . In the case when the radical R is a phenyl ring, the substitute from para position of benzoylic radical does not appear decisive towards activity, these affecting especially the selectivity. Pathol Biol (Paris), 1998 Apr, 46(4), 272 - 8 {Management of epidemics of nosocomial infections}; Astagneau P et al.; Although nosocomial outbreaks contribute less than 10% of all nosocomial infections, they are a significant cause for concern because of their unpredictability, frequent association with instrumentation, and potential lethality in critically-ill patients . Also, they are commonly due to organisms that are atypical or resistant to antimicrobials . As soon as a nosocomial outbreak is suspected, a rigorous investigation should be undertaken . After the appropriate institutional measures, a case-definition should be developed, and the space and time patterns of the cases should be determined . Confirmation should be obtained that the number of cases is larger than usual, and working hypotheses regarding the source and mode of transmission should be developed . Even at this early descriptive stage, recommendations for prevention should be made . If needed, the investigation should be carried further by a case-control study aimed at identifying risk factors, a molecular analysis of the organisms, and examination of samples taken from the environment . A review of hygiene procedures is useful in many cases. Pathol Biol (Paris), 1998 Apr, 46(4), 268 - 71 {Control of nosocomial infections by multiresistant bacteria in geriatric services}; Prieur B et al.; Geriatric wards have a higher prevalence of infection than surgical or acute medical wards, and multiresistant organisms contribute a nonnegligeable proportion of infections in elderly inpatients . The measures used to prevent nosocomial infections in geriatric wards are the same as in other types of wards . They include identifying and ensuring the technical and geographic isolation of colonized and infected patients . Health care providers should be informed of the situation, and antimicrobials used with discernment to avoid the selection of multiresistant organisms . Implementation of these measures is made difficult by architectural factors, the fact that many geriatric patients require assistance in all the activities of daily living, and the long duration of stays in geriatric wards . Additional measures are probably essential to achieve long-term control of nosocomial infections . Insufficient attention has been given to health care providers' perceptions of nosocomial infection and to defining the tasks actually performed by these providers. Orv Hetil, 1998 Sep 13, 139(37), 2179 - 84 {Current problems of antibacterial therapy}; Ludwig E; The development of medicine has been accompanied by the increase of the proportion of immunocompromised patients and as a consequence of antibiotic use, bacterial resistance has reached an unexpected level . Along with these changes, we have been witnessing the rapid development of antimicrobial therapy that comprises several components besides the development of new molecules . The learning of pharmacodynamic effects of particular antibiotic classes can improve the efficacy of therapy and a better cure rate can be achieved in empiric therapy by the knowledge of risk factors and local resistance patterns . It has become clear that an antibiotic policy based exclusively on restriction would result in increased bacterial resistance rate after a temporary decrease of antibiotic cost and was unable to prevent the emerge and spread of multiresistant strains . The solution is the rational and adequate use of antimicrobials, based on the modern theory and practice of antibiotic policy and infection control, that cannot be carried out without the activities of experts in this field. Am J Respir Crit Care Med, 1998 Oct, 158(4), 1156 - 62 Effects of aerosolized interferon-alpha in patients with pulmonary tuberculosis; Giosue S et al.; Interferon-alpha (IFN-alpha) is a cytokine exerting pleiotropic activities, including antimicrobial effects, especially directed against intracellular infectious bacteria . It may be administered by aerosol to reach the lower respiratory tract without systemic side effects . The aim of the study reported here was the evaluation of aerosolized IFN-alpha treatment (3 MU/dose, given three times a week; total study dose: 72 MU/2 mo) in combination with conventional antimycobacterial therapy in patients with pulmonary tuberculosis . Two groups of 10 patients each were compared before and after 2 mo of conventional antituberculous chemotherapy with or without inhaled IFN-alpha . Several biologic (bronchoalveolar lavage fluid {BALF} cellularity, Mycobacterium tuberculosis {MT} number in sputum), biochemical (BALF concentrations of 10 cytokines, BALF IFN-alpha receptor levels), and clinical (fever, vital signs, high-resolution computed tomography {HRCT} images) measures were made in these patients at the time of their enrollment and at the end of the observation period of the study . Fever, MT number in sputum, and abnormalities in HRCT images showed significantly earlier resolution in the IFN-alpha-treated group, together with a more significant decrease in BALF interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) concentrations and significantly greater pre- versus posttreatment variations in IL-2 and IFN-gamma . These data, taken together, suggest that IFN-alpha administration may favorably affect the evolution of pulmonary tuberculosis when combined with antimycobacterial therapy. Rev Cubana Med Trop, 1992, 44(2), 109 - 12 {Sensitivity of Mycobacterium fortuitum by the broth microdilution method determining the inhibitory minimal concentration}; Ferra Salazar C et al.; A study was conducted on 40 Mycobacterium fortuitum strains isolated from symptomatic patients suffering from respiratory diseases and skin lesions . Their susceptibility to different antimicrobial agents was determined by the broth microdilution method, measuring minimal inhibitory concentration . There was sensitivity of the strains to gentamicin and tetracycline as well as resistance to the tuberculostatic drugs used (isoniazid and ethambutol) and cefalotin. Immunology, 1998 Aug, 94(4), 488 - 95 Interferon-gamma-activated primary enterocytes inhibit Toxoplasma gondii replication: a role for intracellular iron; Dimier IH et al.; Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of nucleated cells in its numerous intermediate hosts including man . The oral route is the natural portal of entry of T . gondii . Ingested organisms are released from cysts or oocysts within the gastrointestinal tract and initially invade the intestinal epithelium . We show that T . gondii invades and proliferates in cultured primary rat enterocytes, obtained with an original procedure . Activation of the enterocytes with rat recombinant interferon-gamma (IFN-gamma) inhibits T . gondii replication, the inhibition being dose dependent . Neither nitrogen and oxygen derivatives nor tryptophan starvation appear to be involved in the inhibition of parasite replication by IFN-gamma . Experiments using Fe2+ salt, carrier and chelator indicate that intracellular T . gondii replication is iron dependent, suggesting that IFN-gamma-treated enterocytes inhibit T . gondii replication by limiting the availability of intracellular iron to the parasite . Our data show that enterocytes probably play a major role on mucosal surfaces as a first line of defence against this coccidia, and possibly other pathogens, through an immune mechanism . The results suggest that limiting the availability of iron could represent a broad antimicrobial mechanism through which the activated enterocytes exert control over intracellular pathogens. J Antibiot (Tokyo), 1998 Aug, 51(8), 693 - 8 Demethyl mutactimycins, new anthracycline antibiotics from Nocardia and Streptomyces strains; Speitling M et al.; New anthracycline antibiotics 3'-O-demethyl mutactimycin (3) and 4-O,3'-O-didemethyl mutactimycin (4) were isolated from two actinomycetes strains, Nocardia transvalensis and Streptomyces sp . GW 60/1571 . The chemical structures were elucidated by mass spectrometry and NMR spectroscopy . Antibiotic 3 displayed moderate antimicrobial activity against Gram-positive bacteria and cytotoxicity against P388, L1210 and HeLa tumor cells (IC50; 9.6, >25 and 20 microg/ml, respectively). Eur J Clin Microbiol Infect Dis, 1998 Jul, 17(7), 519 - 21 Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a region of Germany; Wolle K et al.; To evaluate the prevalence of resistance among Helicobacter pylori in Germany, the minimum inhibitory concentrations of amoxicillin, tetracycline, clarithromycin, and metronidazole were determined by means of the E test, for 271 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1996 and 1997 . The prevalence of metronidazole resistance was 32.1%, with resistance found more frequently in women (38.5%) than in men (24.4%) . Clarithromycin resistance was rare (3.3%) . Eight of nine strains resistant to clarithromycin were also resistant to metronidazole . Resistance to either metronidazole or clarithromycin was significantly (P=0.022) higher in patients with duodenal ulcer . No strain was found to be resistant to amoxicillin or tetracycline. Eur J Clin Microbiol Infect Dis, 1998 Jul, 17(7), 505 - 7 Stomatococcus mucilaginosus septicemia in a patient with acute lymphoblastic leukaemia; Trevino M et al.; A 16-year-old patient with acute lymphoblastic leukaemia which had relapsed for the third time developed clinical signs and symptoms of septicemia during a period of neutropenia . The patient had signs of oral mucositis, and Stomatococcus mucilaginosus was isolated from blood cultures . The patient responded well to antibiotic therapy . The biochemical characteristics and antimicrobial susceptibility patterns of 68 other pharyngeal isolates of Stomatococcus mucilaginosus from immunocompromised patients are presented. Farmaco, 1998 Jun 30, 53(6), 425 - 30 Synthesis and antimicrobial activity of coumarin 7-substituted cephalosporins and sulfones; Bonsignore L et al.; Some coumarin 7-substituted cephalosporins and related sulfones were prepared and an antimicrobial assay was performed . The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) carried out on cephalosporins showed a potential activity of some of the synthesized compounds against Gram-positive microorganisms . The tests performed on the corresponding sulfones showed no significant activity, neither as antimicrobial agents nor as inhibitors of beta-lactamase . An association of sulfone 6a with ampicillin was observed to inhibit Gram-positive microorganisms with a lower MIC than for ampicillin alone. Gut, 1998 Jul, 43 Suppl 1, S66 - 9 The European meeting on Helicobacter pylori: therapeutic news from Lisbon; Peitz U et al.; The current standard of Helicobacter pylori treatment has been confirmed by the studies presented at the Lisbon workshop--that is, one of three one week proton pump inhibitor (PPI) based triple therapies comprising a twice daily standard dose of a PPI in combination with two of the following antimicrobial agents: clarithromycin, amoxycillin, or a nitromidazole . This standard of treatment is also highly efficacious and cost-effective in routine community practice . The current data confirm the equivalence of ranitidine bismuth citrate to PPI, and of azithromycin to clarithromycin . The optimum dose for azithromycin has not yet been defined . There is some evidence that in certain regions treatment for more than one week may be advantageous . The reasons are still not clear . However, microbial resistance may be one important factor, as it has a substantial effect on treatment outcome and the prevalence of resistance varies considerably in different areas . The negative impact of resistance is increased by shortening the treatment time . At present, there is no general necessity to test for resistance before treatment . However, before selection of a second line treatment, testing for resistance is recommended. Ned Tijdschr Geneeskd, 1998 Jul 25, 142(30), 1728 - 32 {An rare cause of vaginal discharge: sarcoma botryoides}; Oude Elberink CS et al.; A general practitioner was consulted by a 15-year-old girl, virgo, suffering from foetid vaginal discharge . The girl was seen by a gynaecologist after antimicrobial treatment had failed . Further investigations revealed that a embryonal rhabdomyosarcoma was present, a sarcoma botryoides . The tumour originating from the cervix uteri was resected completely after which chemotherapy was started . One year later there were no sequelae or indications of metastases . Sarcoma botryoides has a better prognosis than other types of rhabdomyosarcoma . The prognosis is also influenced by the site of origin, which is favourable for the cervix. Blood, 1998 Oct 15, 92(8), 2719 - 24 Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B; Ozsahin H et al.; X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells . Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy . Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting . We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and gamma-interferon . During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes . This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions . Clinical and biological signs of infection began to disappear on day 7 post-BMT . Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci . At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection . Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal . FEBS Lett, 1998 Sep 18, 435(2-3), 159 - 62 Novel defensin subfamily from spinach (Spinacia oleracea); Segura A et al.; Antimicrobial peptides (So-D1-7) were isolated from a crude cell wall preparation from spinach leaves (Spinacia oleracea cv . Matador) and, judged from their amino acid sequences, six of them (So-D2-7) represented a novel structural subfamily of plant defensins (group IV) . Group-IV defensins were also functionally distinct from those of groups I-III . They were active at concentrations < 20 microM against Gram-positive (Clavibacter michiganensis) and Gram-negative (Ralstonia solanacearum) bacterial pathogens, as well as against fungi, such as Fusarium culmorum, F . solani, Bipolaris maydis, and Colletotrichum lagenarium . Fungal inhibition occurred without hyphal branching . Group-IV defensins were preferentially distributed in the epidermal cell layer of leaves and in the subepidermal region of stems. Pharm World Sci, 1998 Aug, 20(4), 149 - 60 Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis; Touw DJ; The disposition of many drugs in cystic fibrosis is abnormal compared with healthy individuals . In general, changes include an increased volume of distribution expressed in liters per kg bodyweight for highly hydrophilic drugs such as aminoglycosides, and, to a lesser extent, for penicillins and cephalosporins, together with an increased total body clearance . The main reason for the increased volume of distribution is the increased amount of lean tissue per kg bodyweight, since patients with CF are generally undernourished and have a paucity of adipose tissue . The reason for the increased renal clearance is less clear . Increased glomerular filtration and tubular secretion have been observed . Protein binding generally is unaltered in CF . The fluorquinolones and vancomycin show no altered pharmacokinetics in CF although gastro-intestinal absorption may be delayed for fluorquinolones . Sulphamethoxazole shows increased clearance due to an increased acetylation and, in the case of trimethoprim, renal clearance is increased compared with healthy individuals . As a consequence, drugs that show increased clearance, will lead to reduced serum concentrations and smaller AUCs and therefore CF patients require larger doses per kg bodyweight. Ann Pharmacother, 1998 Sep, 32(9), 915 - 28 Update on drug interactions with azole antifungal agents; Lomaestro BM et al.; OBJECTIVE: To review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole . DATA SOURCES: Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term "interaction" as MeSH headings . Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996 . STUDY SELECTION: Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included . In vitro data were selected from literature review and citations . DATA EXTRACTION: Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided . DATA SYNTHESIS: The incidence of fungal infections and consequent azole antifungal usage continues to increase . By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions . The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant . CONCLUSIONS: The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions . Recent data have increased our understanding of drug--drug interactions with azoles . Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care. Gastroenterol Clin Biol, 1998 Apr, 22(4), 407 - 12 {Comparison of quantifying Helicobacter pylori gastric infection by culture, histology and C13 urea breath test}; Auroux J et al.; OBJECTIVES: In Helicobacter pylori infection, the bacterial burden may play a role in the pathogenesis of gastric or duodenal ulcerated lesions . It could also influence the results of antimicrobial therapy . No simple test has been validated to quantify Helicobacter pylori density . The aim of this study was to determine the value of histology and/or 13C-urea breath test to quantify the infection as compared with quantitative culture, taken as a reference method . PATIENTS AND METHODS: Biopsies samples were taken from the antrum at endoscopy in 72 patients . Thirty-seven patients with positive urease test at 20 minutes were enrolled in the study . Bacterial density was evaluated from biopsies by quantitative culture and semi-quantitative histological examination (score from 0 to 3) . The bacterial density was evaluated as well by 13C-urea breath test from the proportion of 13CO2 in exhaled air (delta 13CO2) at 20, 40, and 60 minutes as compared with the basal level . RESULTS: The bacterial density, evaluated by quantitative culture ranged from 5 CFU to 110,000 CFU per mg of tissue . By histology, a score 1 was found in 5 patients, a score 2 in 17, and a score 3 in 15 . delta of 13CO2 measured by 13C-urea breath test ranged from 0.2 to 117.5, from 0.2 to 102, and from 0.6 to 66.7 at 20, 40 and 60 minutes respectively . The quantity of bacteria measured by culture was not significantly higher for these with a score of 3 as compared with those with a pooled score of 1 and 2 (P < 0.05) . No significant correlation was found between the results of quantitative culture and these of breath test . CONCLUSION: In practice, evaluation of bacterial burden by a histological score seems only accurate for the most severe density (score 3) . The 13C-urea breath test does not allow a reliable quantitative evaluation. Int J Food Microbiol, 1998 Aug 18, 43(1-2), 73 - 9 Relationship between volatile components of citrus fruit essential oils and antimicrobial action on Penicillium digitatum and penicillium italicum; Caccioni DR et al.; This study examined the effect of volatile components of citrus fruit essential oils on P . digitatum and P . italicum growth . The hydrodistilled essential oils of orange (Citrus sinensis cvv . "Washington navel", "Sanguinello", "Tarocco", "Moro", "Valencia late", and "Ovale"), bitter (sour) orange (C . aurantium), mandarin (C . deliciosa cv . "Avana"), grapefruit (C . paradisi cvv . "Marsh seedless" and "Red Blush"), citrange (C . sinensis x Poncirus trifoliata cvv . "Carrizo" and "Troyer"), and lemon (C . limon cv . "Femminello", collected in three periods), were characterized by a combination of GC and GC/MS analyses . The antifungal efficacy of the oils was then examined at progressively reduced rates . Findings showed a positive correlation between monoterpenes other than limonene and sesquiterpene content of the oils and the pathogen fungi inhibition . The best results were shown by the citrange oils, whose chemical composition is reported for the first time, and lemon . Furthermore P . digitatum was found to be more sensitive to the inhibitory action of the oils. J S Afr Vet Assoc, 1998 Jun, 69(2), 55 - 6 Lack of susceptibility of Ehrlichia canis to imidocarb dipropionate in vitro; Kelly PJ et al.; In vitro antimicrobial susceptibility testing was used to compare the efficacy of imidocarb dipropionate and doxycycline on the growth of Ehrlichia canis in DH82 cell cultures . Over a 9-day period there were no significant differences (p < 0.01) in the growth of E . canis in untreated control wells and those to which imidocarb dipropionate was added at 1.2, 2.4, 4.8 or 12 micrograms/ml for the 1st 3 days . Average infection rates rose from 50 to 55% on day 0 to 100% on day 5 or 6 . Doxycycline at 1 microgram/ml had residual or rickettsiocidal activity against E . canis with the average percentages of DH82 cells infected declining from 51 to 24% while the organism was exposed to the drug (3 days) and from 21 to 2% in the 6 days following removal of the drug from the cell culture medium. Arch Pediatr, 1998, 5 Suppl 3, 296S - 301S {Antibiotic treatment of acute pyelonephritis in the child}; Begue P; Antimicrobial therapy for pyelonephritis in children must quickly eradicate the bacterial infection and prevent scars in renal parenchyma . Escherichia coli (E Coli) is found in about 90% of cases of acute pyelonephritis in outpatients, 40% of E coli being ampicillin-resistant . The present effective antibiotics are: 3rd-generation cephalosporines, amoxicillin-clavulanic acid association, and aminoglycosides . In the literature therapeutical guides are divergent concerning the route of administration (oral or i.v.), mono or bitherapy, the duration of the treatment (usually for 10 days), and the need for hospitalisation . The criteria for choice are risk factors such as: very young age (< 6 months), fever with toxic symptoms, vomiting, dehydration, uropathy, and poor compliance . There are few long term studies which compare two, therapeutic regimens and no evaluation of the frequency of consequent chronic pyelonephritis in adult age has taken place . Recent data suggest that an oral sequential treatment may permit a shorter hospital stage . The trend is chiefly to do bona fide recommendations more than elaboration of a true consensus. Arch Intern Med, 1998 Sep 28, 158(17), 1916 - 22 Factors related to in-hospital deaths in patients with tuberculosis; Sacks LV et al.; BACKGROUND: Deaths from tuberculosis (TB) continue to occur despite the availability of effective antimicrobial agents . Multidrug resistance, human immunodeficiency virus (HIV) infection, and delayed therapy have been implicated . OBJECTIVE: To examine clinical factors associated with in-hospital death in patients with active TB . METHODS: A retrospective case-control study was performed on patients admitted to a government hospital in Johannesburg, South Africa, used as a referral center for patients with TB . Eighty patients admitted with TB who died during hospitalization were matched with 80 similar patients with TB who survived hospitalization . Clinical, demographic, and radiological characteristics of each group were compared . RESULTS: In-hospital fatalities were associated with female sex (P=.01), lower admission hemoglobin level (P<.01), and weight (P<.01), and a trend to more extensive infiltrative patterns on chest radiographs . Multidrug resistance, extrapulmonary disease, and HIV infection were unexpectedly not related to in-hospital mortality . High mortality in the first weeks of admission suggested that late presentation was a major factor for in-hospital death . The HIV-infected participants in the study showed less drug resistance than HIV-negative patients (P=.07), equivalent extents of infiltrative patterns on chest radiographs, but much less cavitation and fibrosis (P<.01) . CONCLUSIONS: Clinical predictors of early mortality from TB included anemia, low body weight, and extensive infiltrates, while multidrug resistance and HIV infection were not significant factors . Previous exposure to TB and delayed presentation may have influenced our findings . Since patients present late in their illness, aggressive case finding would be important in controlling TB in this population. Lab Invest, 1998 Sep, 78(9), 1121 - 9 Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis; Redl B et al.; Members of the lipocalin protein family are characterized by their ability to bind small hydrophobic molecules . Some of them are known to be produced by various glands and secretory cells . Under certain conditions, these proteins would be ideally suited for clearance of lipophilic, potentially harmful substances and might also act as protection factors in airway secretions . We therefore used RT-PCR analysis with a set of oligonucleotide primers deduced from conserved regions of lipocalin members to identify specific RNA isolated from human trachea . With two of these oligonucleotide primers, a positive result was obtained . Sequencing of the RT-PCR products revealed that the DNA fragments were identical to the lipocalin 1 (LCN1) encoding cDNA . LCN1 is an unusual lipocalin member that binds a variety of lipophilic compounds and exhibits cysteine proteinase inhibitor and antimicrobial activities . The local production and topographic distribution of LCN1 in the human tracheobronchial tree was then investigated by immunoperoxidase staining on thin-layer sections using a specific antiserum . LCN1 was detectable in the acini of serous mucosal glands and sometimes within the glandular lumen, suggesting excretion of the protein . The latter finding was tested and verified by Western blot analysis of bronchial secretions of healthy individuals . Furthermore, the results of SDS-PAGE and Western blot analysis of bronchial secretions from patients with cystic fibrosis (CF), which are usually characterized by an increase of airway lipids, suggested that LCN1 secretion was enhanced . Northern blot analysis of RNA from normal trachea and RNA isolated from tracheal biopsies of patients with CF indicated that induced secretion was due to an up-regulated expression of the LCN1 gene . Thus, our investigations present the first clear evidence that LCN1 is induced in infection or inflammation and support the idea that this lipocalin functions as a physiologic protection factor of epithelia in vivo. Crit Rev Food Sci Nutr, 1998 Aug, 38(6), 421 - 64 Tannins and human health: a review; Chung KT et al.; Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that are present in many plant foods . They have been reported to be responsible for decreases in feed intake, growth rate, feed efficiency, net metabolizable energy, and protein digestibility in experimental animals . Therefore, foods rich in tannins are considered to be of low nutritional value . However, recent findings indicate that the major effect of tannins was not due to their inhibition on food consumption or digestion but rather the decreased efficiency in converting the absorbed nutrients to new body substances . Incidences of certain cancers, such as esophageal cancer, have been reported to be related to consumption of tannins-rich foods such as betel nuts and herbal teas, suggesting that tannins might be carcinogenic . However, other reports indicated that the carcinogenic activity of tannins might be related to components associated with tannins rather than tannins themselves . Interestingly, many reports indicated negative association between tea consumption and incidences of cancers . Tea polyphenols and many tannin components were suggested to be anticarcinogenic . Many tannin molecules have also been shown to reduce the mutagenic activity of a number of mutagens . Many carcinogens and/or mutagens produce oxygen-free radicals for interaction with cellular macromolecules . The anticarcinogenic and antimutagenic potentials of tannins may be related to their antioxidative property, which is important in protecting cellular oxidative damage, including lipid peroxidation . The generation of superoxide radicals was reported to be inhibited by tannins and related compounds . The antimicrobial activities of tannins are well documented . The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins . We have also found that tannic acid and propyl gallate, but not gallic acid, were inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing microorganisms . Their antimicrobial properties seemed to be associated with the hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after ripening of many edible fruits . Tannins in these fruits thus serve as a natural defense mechanism against microbial infections . The antimicrobial property of tannic acid can also be used in food processing to increase the shelf-life of certain foods, such as catfish fillets . Tannins have also been reported to exert other physiological effects, such as to accelerate blood clotting, reduce blood pressure, decrease the serum lipid level, produce liver necrosis, and modulate immunoresponses . The dosage and kind of tannins are critical to these effects . The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannins on human health. C R Seances Soc Biol Fil, 1998, 192(3), 445 - 62 {Scorpion toxins and defensins}; Goyffon M et al.; The scorpion venoms possess many neurotoxic peptides which constitute a group of molecular families with a common architecture and a high degree of polymorphism . This architecture is found also in circulating antimicrobial peptides belonging to the defensins family, which are especially structurally related to the blocking potassium channels neurotoxins . The diversification in functions with a unique architectural scheme is discussed taking in account the biophysiological characteristics of the scorpion order. Appl Environ Microbiol, 1998 Oct, 64(10), 4047 - 52 Specific cell wall proteins confer resistance to nisin upon yeast cells; Dielbandhoesing SK et al.; The cell wall of a yeast cell forms a barrier for various proteinaceous and nonproteinaceous molecules . Nisin, a small polypeptide and a well-known preservative active against gram-positive bacteria, was tested with wild-type Saccharomyces cerevisiae . This peptide had no effect on intact cells . However, removal of the cell wall facilitated access of nisin to the membrane and led to cell rupture . The roles of individual components of the cell wall in protection against nisin were studied by using synchronized cultures . Variation in nisin sensitivity was observed during the cell cycle . In the S phase, which is the phase in the cell cycle in which the permeability of the yeast wall to fluorescein isothiocyanate dextrans is highest, the cells were most sensitive to nisin . In contrast, the cells were most resistant to nisin after a peak in expression of the mRNA of cell wall protein 2 (Cwp2p), which coincided with the G2 phase of the cell cycle . A mutant lacking Cwp2p has been shown to be more sensitive to cell wall-interfering compounds and Zymolyase (J . M . Van der Vaart, L . H . Caro, J . W . Chapman, F . M . Klis, and C . T . Verrips, J . Bacteriol . 177:3104-3110, 1995) . Here we show that of the single cell wall protein knockouts, a Cwp2p-deficient mutant is most sensitive to nisin . A mutant with a double knockout of Cwp1p and Cwp2p is hypersensitive to the peptide . Finally, in yeast mutants with impaired cell wall structure, expression of both CWP1 and CWP2 was modified . We concluded that Cwp2p plays a prominent role in protection of cells against antimicrobial peptides, such as nisin, and that Cwp1p and Cwp2p play a key role in the formation of a normal cell wall. Eur J Clin Microbiol Infect Dis, 1998 Jun, 17(6), 391 - 3 Comparison of three media for agar dilution susceptibility testing of Bordetella pertussis using six antibiotics; Hoppe JE et al.; Since antimicrobial susceptibility testing of the fastidious species Bordetella pertussis is not standardized, the most suitable medium for agar dilution testing of this species has not yet been determined . In the present study, Mueller-Hinton, Bordet-Gengou, and Oxoid charcoal agars (each supplemented with 5% horse blood) were evaluated for agar dilution susceptibility testing of Bordetella pertussis against ampicillin, chloramphenicol, ciprofloxacin, doxycycline, erythromycin, and trimethoprim-sulfamethoxazole . Mueller-Hinton agar was the most suitable medium. Ther Umsch, 1998 Aug, 55(8), 493 - 7 {Therapeutic management of neurodermatitis atopica}; Kagi MK; The therapy of atopic dermatitis remains a challenge . The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens . During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended . Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations . Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis. Clin Pharmacol Ther, 1998 Sep, 64(3), 278 - 85 Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences; Greenblatt DJ et al.; BACKGROUND: Macrolide antimicrobial agents may impair hepatic clearance of drugs metabolized by cytochrome P4503A isoforms . Potential interactions of triazolam, a substrate metabolized almost entirely by cytochrome P4503A in humans, with 3 commonly prescribed macrolides were identified using an in vitro metabolic model . The actual interactions, and their pharmacodynamic consequences, were verified in a controlled clinical study . METHODS: In an in vitro model using human liver microsomes, 250 mumol/L triazolam was incubated with ascending concentrations (0 to 250 mumol/L of troleandomycin, azithromycin, erythromycin, and clarithromycin . In a randomized, double-blind, 5-trial clinical pharmacokinetic-pharmacodynamic study, 12 volunteers received 0.125 mg triazolam orally, together with placebo, azithromycin, erythromycin, or clarithromycin . In a fifth trial they received placebo plus placebo . RESULTS: Mean 50% inhibitory concentrations versus 4-hydroxytriazolam formation in vitro were as follows: 3.3 mumol/L troleandomycin, 27.3 mumol/L erythromycin, 25.2 mumol/L clarithromycin, and greater than 250 mumol/L azithromycin . Apparent oral clearance of triazolam when given with placebo or azithromycin was nearly identical (413 and 416 mL/min), as were peak plasma concentrations (1.25 and 1.32 ng/mL) and elimination half-life (2.7 and 2.6 hours) . Apparent oral clearance was significantly reduced (P < .05) during erythromycin and clarithromycin trials (146 and 95 mL/min) . Peak plasma concentration was correspondingly increased, and elimination half-life was prolonged . The effects of triazolam on dynamic measures were nearly identical when triazolam was given with placebo or azithromycin, but benzodiazepine agonist effects were enhanced during erythromycin and clarithromycin trials . CONCLUSION: The in vitro model identifies macrolides that may impair triazolam clearance . Anticipated interactions, and their pharmacodynamic consequences in volunteer subjects, were verified in vivo. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2765 - 7 PMX-622 (polymyxin B-dextran 70) does not alter in vitro activities of 11 antimicrobial agents; Fuchs PC et al.; Because of its capacity to neutralize the lethality of gram-negative bacterial endotoxic lipopolysaccharides, PMX-622 (polymyxin B bound to dextran 70) is being developed for possible adjunctive therapy of gram-negative sepsis . In this study, it was determined that the in vitro antimicrobial activity of PMX-622 was minimal and that it does not interfere with the in vitro antimicrobial activity of 11 antibiotics commonly used to treat gram-negative infections. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2694 - 9 Translation elongation factor 2 is part of the target for a new family of antifungals; Capa L et al.; Translation elongation factor 2 (EF2), which in Saccharomyces cerevisiae is expressed from the EFT1 and EFT2 genes, has been found to be targeted by a new family of highly specific antifungal compounds derived from the natural product sordarin . Two complementation groups of mutants resistant to the semisynthetic sordarin derivative GM193663 were found . The major one (21 members) consisted of isolates with mutations on EFT2 . The minor one (four isolates) is currently being characterized but it is already known that resistance in this group is not due to mutations on EFT1, pointing to the complex structure of the functional target for these compounds . Mutations on EF2 clustered, forming a possible drug binding pocket on a three-dimensional model of EF2, and mutant cell extracts lost the capacity to bind to the inhibitors . This new family of antifungals holds the promise to be a much needed and potent addition to current antimicrobial treatments, as well as a useful tool for dissection of the elongation process in ribosomal protein synthesis. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2595 - 601 Targeted antimicrobial photochemotherapy; Soukos NS et al.; This study explores a new approach for antimicrobial therapy with light activation of targeted poly-L-lysine (pL)-chlorin e6 (ce6) conjugates . The goal was to test the hypothesis that these conjugates between pL and ce6 would efficiently target photodestruction towards gram-positive (Actinomyces viscosus) and gram-negative (Porphyromonas gingivalis) oral species while sparing an oral epithelial cell line (HCPC-1) . Conjugates of ce6 with pL (average molecular weight, 2,000) having a positive, neutral, or negative charge were prepared . Illumination with red light (lambdamax = 671 nm) from a diode array produced a dose-dependent loss of CFU from the bacteria, under conditions that did not affect the viability of the epithelial cells . For P . gingivalis, the cationic conjugate produced 99% killing, while the neutral conjugate killed 91% and the anionic conjugate killed 76% after 1 min of incubation and exposure to red light for 10 min . For A . viscosus, the cationic conjugate produced >99.99% killing while HCPC-1 cells remained intact . The importance of the positive charge was shown by the effectiveness of ce6-monoethylenediamine monoamide (a monocationic derivative of ce6) in killing both bacteria . The clinically employed benzoporphyrin derivative under the same conditions killed epithelial cells while leaving P . gingivalis relatively unharmed . A mixture of ce6 with pL did not show phototoxicity comparable with that of the cationic conjugate . These results were explained by the selective uptake of the conjugates by bacteria (20- to 100-fold) compared to that by mammalian cells, while free ce6 showed much less selectivity for bacteria (5- to 20-fold) . The data suggest that the cationic pL-ce6 conjugate may have an application for the photodynamic therapy of periodontal disease. Antimicrob Agents Chemother, 1998 Oct, 42(10), 2492 - 4 Mucoadhesive microspheres containing amoxicillin for clearance of Helicobacter pylori; Nagahara N et al.; In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared . The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil . The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension . The in vivo clearance of H . pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions . The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H . pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used . In conclusion, the mucoadhesive microspheres more effectively cleared H . pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion . A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H . pylori. Chemotherapy, 1998 Nov-Dec, 44(6), 427 - 35 New strategies in the treatment of infectious complications in haematology and oncology: is there a role for out-patient antibiotic treatment of febrile neutropenia? Karthaus M, Carratala J, Jurgens H, Ganser A. Febrile neutropenia is associated with a significant risk of complications and mortality . Patients with neutropenia secondary to cytostatic chemotherapy who develop fever are normally admitted to hospital and treated promptly with broad-spectrum antibiotics . Over the last 10 years, chemotherapy for solid tumours has been shifting out of the hospital setting into the ambit of community-based oncologists, and out-patient treatment with complex multidrug protocols is becoming increasingly common . In North America high-dose protocols combined with peripheral blood stem cell transfusion are already being administered on an out-patient basis . With the increase in the numbers of out-patients undergoing multidrug chemotherapy, there has been a corresponding rise in the severity and duration of neutropenia and in the incidence of associated infections . Patients with neutropenia of short duration (<7 days) and fever are at a relatively low risk for complications, and in these circumstances, out-patient antibiotic treatment is an alternative to costly hospitalisation . Drugs, whose antimicrobial coverage and pharmacokinetics make them particularly suitable for out-patient treatment of febrile neutropenia, include intravenous and oral quinolones and, for once-daily dosing, intravenous glycopeptides, ceftriaxone and intravenous aminoglycosides . Response rates of 60-95% have been achieved with such regimens in clinical trials, with hospital admission avoided in 75-95% of the cases . There is no doubt that out-patient treatment improves the quality of life of cancer patients . In Europe, however, there is a need for randomised clinical trials to support the establishment of out-patient-based treatment of febrile neutropenia . Out-patient antibiotic treatment of febrile neutropenia is still not standard practice, and community-based providers of such treatment must be adequately equipped and experienced in the management of this condition. Int J Tuberc Lung Dis, 1998 Sep, 2(9), 751 - 5 E-test for susceptibility testing of Mycobacterium tuberculosis; Hausdorfer J et al.; SETTING: Initial isolates should be tested for drug susceptibility to confirm the anticipated effectiveness of chemotherapy . OBJECTIVE: To evaluate E-test strips for susceptibility testing of Mycobacterium tuberculosis . DESIGN: A proportion method using Lowenstein-Jensen medium and the Bactec radiometric system were compared with the E-test (isoniazid {INH}, rifampicin {RMP}, ethambutol {EMB} and streptomycin {SM}) . RESULTS: For 73 of the 81 M . tuberculosis isolates (90.1%) the proportion and E-test methods yielded concordant susceptibility results against all four antimicrobial agents tested . Of these 73 strains, 69 were fully susceptible; the four isolates showing resistance to antimicrobial drugs by both methods were also resistant when tested by Bactec 460TB . While the proportion method indicated susceptibility for the eight remaining strains, E-test results showed mono EMB resistance in five strains, INH resistance for two isolates (including one isolate resistant to EMB plus INH), and for one strain E-test yielded resistance to EMB and SM . Using Bactec as the reference method, the E-test resulted in false resistance in eight strains and no false susceptibility . CONCLUSION: Due to a substantial rate of false resistance, this method cannot be recommended at present for practical use in clinical laboratories. Mycopathologia, 1998, 141(3), 115 - 21 Antimicrobial susceptibilities of strains of Nocardia brasiliensis isolated from soil of Tucumán; van Gelderen de Komaid AA et al.; The activity of antimicrobial agents against soil isolates of N . brasiliensis was studied by determination of the minimum inhibitory concentrations (MICs) and disk diffusion technique, according to the National Committee for Clinical Laboratory Standards (NCCLS) . The objectives were: (a) to study the patterns of sensitivity among regional strains of N . brasiliensis isolated from natural sources (soil) of different zones of Tucuman province; (b) to correlate these results with those previously obtained with regional strains of N . brasiliensis isolated from human mycetomas, as a contribution in the evaluation of the importance of the natural reservoir area of the potentially pathogen strains . The results obtained by both methods identified strains of N . brasiliensis from soils with similar patterns of susceptibility to the strains N . brasiliensis isolated from human mycetomas . This showed strains sensitive and resistant to antibiotics . The majority of the isolates of N . brasiliensis from soils showed higher susceptibilities to antibiotics than the strains isolated from human mycetomas . Among the antibiotics studied, cefotaxime, ceftriaxone and gentamicin were the most effective against all the regional strains tested, and these results are correlated with those obtained with regional strains that cause human mycetomas. Pediatrics, 1998 Oct, 102(4 Pt 1), 905 - 8 Lyme arthritis in children: clinical epidemiology and long-term outcomes; Gerber MA et al.; OBJECTIVE: Although Lyme disease has become a relatively common cause of arthritis among children in areas of the country in which the disease is endemic, little information is available about the clinical epidemiology and long-term outcomes of children with Lyme arthritis . We conducted a long-term follow-up study to determine the clinical epidemiology of Lyme arthritis in children as well as their long-term outcomes . PATIENTS AND METHODS: All children seen between 1982 and 1991 at the Pediatric Rheumatology Clinic at Newington Children's Hospital (Newington, CT) with an initial diagnosis of Lyme disease were identified . Medical records were reviewed and structured telephone interviews were conducted to obtain demographic, clinical, and follow-up data . RESULTS: A total of 90 children (63% boys) with a mean age of 8.3 years (range, 1.8-16 years) at the time of diagnosis of Lyme arthritis were evaluated . Lyme arthritis was preceded by early Lyme disease in 23 (26%) of the children; however, only 8 (35%) of these children had been treated with appropriate antimicrobial therapy at that early stage . Ninety percent of the children had arthritis of at least one knee, while small joints were rarely involved . For the 31 children who underwent arthrocentesis, the mean white blood cell count in the synovial fluid was 38 000 cells/mm3 (range, 7000-99 000 cells/mm3) with predominantly neutrophils . For the 79 children for whom an erythrocyte sedimentation rate was determined, the highest level for 61 (77%) was >20 mm/h and for 36 (46%) was >50 mm/h . Antimicrobial therapy was initiated 2 days to 5.5 years (median, 2 months) after the onset of symptoms . However, 5 of the children were never treated with antimicrobials . Fifty-one percent of the patients had a single episode of arthritis, while 49% reported recurrent episodes of arthritis over a period of 1 week to 8 years (median, 6 months) . Two children (2%) developed chronic arthritis and underwent arthroscopic synovectomy . At the time of the telephone follow-up evaluation, performed 2 to 12 years (median, 7 years) after the onset of the Lyme arthritis, 4 children had ongoing musculoskeletal complaints that resulted in mild to moderate impairment of school or sports activities, but none of the children had evidence of active arthritis . CONCLUSION: The results of this investigation suggest that the prognosis for children with Lyme arthritis who are treated with appropriate antimicrobial therapy is excellent. Pediatrics, 1998 Oct, 102(4 Pt 1), 879 - 84 A novel use of xylitol sugar in preventing acute otitis media; Uhari M et al.; BACKGROUND: Xylitol, a commonly used sweetener, is effective in preventing dental caries . As it inhibits the growth of pneumococci, we evaluated whether xylitol could be effective in preventing acute otitis media (AOM) . DESIGN: Altogether, 857 healthy children recruited from day care centers were randomized to one of five treatment groups to receive control syrup (n = 165), xylitol syrup (n = 159), control chewing gum (n = 178), xylitol gum (n = 179), or xylitol lozenge (n = 176) . The daily dose of xylitol varied from 8.4 g (chewing gum) to 10 g (syrup) . The design was a 3-month randomized, controlled trial, blinded within the chewing gum and syrup groups . The occurrence of AOM each time the child showed any symptoms of respiratory infection was the main outcome . RESULTS: Although at least one event of AOM was experienced by 68 (41%) of the 165 children who received control syrup, only 46 (29%) of the 159 children receiving xylitol syrup were affected, for a 30% decrease (95% confidence interval {CI}: 4.6%-55.4%) . Likewise, the occurrence of otitis decreased by 40% compared with control subjects in the children who received xylitol chewing gum (CI: 10.0%-71.1%) and by 20% in the lozenge group (CI: -12.9%-51.4%) . Thus, the occurrence of AOM during the follow-up period was significantly lower in those who received xylitol syrup or gum, and these children required antimicrobials less often than did controls . Xylitol was well tolerated . CONCLUSIONS: Xylitol sugar, when given in a syrup or chewing gum, was effective in preventing AOM and decreasing the need for antimicrobials. Ophthalmology, 1998 Sep, 105(9), 1652 - 8 Nontuberculous mycobacterial keratitis in south Florida; Ford JG et al.; OBJECTIVE: This study aimed to review the clinical features, therapeutic response, and histopathology of cases of nontuberculous mycobacterial keratitis at the Bascom Palmer Eye Institute . DESIGN AND PARTICIPANTS: Retrospective review of medical records, clinical photographs, histopathology, and microbiology of 24 cases of nontuberculous acid-fast keratitis over the past 15 years . RESULTS: Causal organisms included Mycobacterium chelonae (16), M . fortuitum (3), M . avium-intracellulare (2), M . nonchromogenicum (1), M . triviale (1), and M . asiaticum (1) . Clinically, the keratitis had a superficial location except in those patients with a history of surgery . Amikacin was the most commonly used antibiotic (63%) . Three patients were treated with Clarithromycin . In one patient, it was stopped because of toxicity; the other two had resolution of their infiltrates . Fifty-five percent did not respond to topical antimicrobial therapy . The organisms as a group were sensitive to amikacin and Clarithromycin and resistant to the fluoroquinolones . Sixty-four percent of the group that failed to respond to medical treatment were treated with steroids after the diagnosis was known, in comparison to 44% of the group treated successfully with medications . The histopathology of the patients treated with steroids showed minimal inflammation despite a large number of organisms, in contrast to the dense infiltrates seen in the specimens from patients not treated with topical steroids . CONCLUSION: Nontuberculous mycobacterial keratitis is a chronic insidious infection that is often unresponsive to medical therapy . The authors recommend that steroids be withheld . Based on the authors' experience of three patients, topical Clarithromycin may hold promise as a therapeutic agent . Lamellar keratectomy or penetrating keratoplasty should be considered in those patients who do not respond to medical therapy or those who have recurrent exacerbations on attempted weaning of topical antibiotic therapy. Biochemistry, 1998 Sep 29, 37(39), 13791 - 9 Insertion of magainin into the lipid bilayer detected using lipid photolabels; Jo E et al.; We investigated the interaction of the antimicrobial peptides Ala19-magainin 2 amide and magainin 2 amide with lipid using two lipid photolabels, azidobenzoyl galactosylceramide (GalCer-PL) and azidobenzoylamido capryloyl galactosylceramide (GalCer-C8-PL), which position their photosensitive groups near the apolar-polar interface and near the center of the bilayer, respectively . Magainins have been postulated to permeabilize membranes either by inserting in a transmembrane fashion into the bilayer and forming a channel or by binding to the surface of the bilayer and disturbing lipid packing . Evidence for channel formation has been difficult to obtain, possibly because only a fraction of the peptide may form a channel at any one time and because the channels may have a short lifetime . Both photolabels significantly labeled the peptides when bound to acidic phospholipid vesicles . The extent of labeling by GalCer-C8-PL was at least 70% of that by GalCer-PL, indicating that some of the peptide was inserted deeply into the bilayer at least transiently . The extent of labeling of Ala19-magainin 2 amide increased significantly with an increase in the peptide to lipid mole ratio, indicating cooperativity and supporting the channel model . The extent of labeling of this peptide was maximal by 30 s and did not change over 30 min, indicating that peptide insertion is rapid and either that the peptide remains inserted for at least 30 min or that equilibrium between inserted and noninserted peptide is achieved by 30 s . The latter is supported by other studies in the literature . Use of this hydrophobic photolabeling technique has permitted detection of peptide monomers which inserted into the bilayer and/or formed a channel at some time during the labeling procedure. Obstet Gynecol Surv, 1998 Sep, 53(9), 575 - 85 Nutritional and antimicrobial interventions to prevent preterm birth: an overview of randomized controlled trials; Villar J et al.; The study was conducted to assess the effectiveness of interventions for the prevention or treatment of nutritional and infectious disorders during pregnancy on preterm birth rates . Cochrane systematic reviews or any other more up-to-date systematic review of antimicrobial and nutritional interventions were sought . Electronic searches of the Cochrane Controlled Trials Register were carried out to identify any trials published since the most recent update of the systematic review . Also, authors of Cochrane systematic reviews, which have not been updated recently, were contacted regarding new information . Systematic reviews of nutritional and antimicrobial interventions during pregnancy, reporting preterm delivery rates (delivery before 37 weeks) and "prematurity" (including low birth weight) either as primary or secondary outcomes, were included . General interventions without a specific nutritional supplementation or antimicrobial component were not considered for inclusion . Interventions to stop labor or prolong pregnancy after a diagnosis of preterm labor were excluded . For each systematic review, data on preterm delivery rate by intervention group was obtained . The total number of trials in the review, number of trials reporting preterm birth as an outcome, number of participants and events have been systematically extracted . Eighteen systematic reviews (10 nutritional and 8 antimicrobial) were considered . Our results indicated that, overall, the treatment of asymptomatic bacteriuria reduces the incidence of preterm birth or low birth weight (< 2500 gm) (typical relative risk (RR): 0.67; 95 percent confidence interval (CI): 0.52-0.85) . The protective effect of treating asymptomatic bacteriuria for preterm delivery persisted when only the three trials reporting preterm delivery (< 37 weeks) were included in the meta-analysis (typical RR: 0.53, 95 percent CI: 0.33-0.86) . Routine iron supplementation prevents maternal anemia and one trial comparing routine versus selective iron supplementation showed a statistically nonsignificant reduction in preterm birth . Zinc, magnesium, and fish oil supplementations show promising results in reducing preterm birth, but the evidence is not strong . Calcium supplementation remains controversial, although there was a statistically significant reduction in preterm delivery in the subgroup of women at high risk of developing hypertension during pregnancy . Two trials with use of metronidazole (alone or with erythromycin) showed a reduction in preterm delivery in women who were at a high risk of preterm delivery and had bacterial vaginosis at screening . We have concluded that asymptomatic bacteriuria should be screened and treated in all settings that offer antenatal care . Single dose treatment seems to be as effective as longer (4-7 days) treatment, although this needs to be confirmed by a large, methodologically rigorous trial . There are a number of promising interventions such as calcium supplementation in women with low calcium intake, iron, zinc, magnesium, and fish oil supplementation, and treatment of bacterial vaginosis in women at high risk of preterm delivery that need additional research to determine a possible role for prevention of preterm delivery. Prikl Biokhim Mikrobiol, 1998 Jul-Aug, 34(4), 419 - 25 {Coimmobilization on unmodified polymers of the proteolytic enzyme protease S and antimicrobial drugs}; Skokova IF et al.; In order to develop materials of prolonged biological effects, the proteolytic enzyme protease S was coimmobilized with antimicrobial drugs chlorhexidine bigluconate and gentamicin sulfate on unmodified cellulose and polyester fibrous materials . The drugs were incorporated into the polymeric composition, which was attached to the materials studied. Biochim Biophys Acta, 1998 Sep 8, 1387(1-2), 239 - 48 Structure-activity analysis of brevinin 1E amide, an antimicrobial peptide from Rana esculenta; Kwon MY et al.; Brevinin 1E, consisting of 24 amino acid residues, from Rana esculenta has potent antimicrobial and hemolytic activity . From a structural point of view, this peptide has a N-terminal hydrophobic region, a proline hinge region in the middle and a C-terminal loop region delineated by an intra-disulfide bridge, which is a common structural feature of antimicrobial peptides from Rana species . To investigate the structural features for antimicrobial and hemolytic activity, truncated and linearized brevinin 1E amides were synthesized and characterized . A deletion of three amino acids from the N-terminal region did not greatly affect antimicrobial activity but dramatically reduced hemolytic activity . The contribution of the intra-disulfide bridge to antimicrobial and hemolytic activity was somewhat different between brevinin 1E amide and truncated fragments . In brevinin 1E amide, the elimination of the intra-disulfide bridge did not greatly affect antimicrobial and hemolytic activity whereas the elimination of the intra-disulfide bridge in the truncated fragments did not decrease antimicrobial activity but did decrease hemolytic activity . Circular dichroism spectra and the retention time on the C18 reverse phase column revealed that the intra-disulfide bridge (i, i+6) formed an amphipathic loop which increased hydrophobicity and helped to induce the alpha-helical structure in the membrane-mimetic environment . Even though the intra-disulfide bridge and the N-terminal region were responsible for the alpha-helical structure and hydrophobicity, these two structural features were not essential for antimicrobial activity . The hemolytic activity of brevinin 1E amide and its analogs also correlated well with the retention time rather than the alpha-helicity. J Nat Prod, 1998 Sep, 61(9), 1082 - 5 New melampolides from Schkuhria schkuhrioides; Delgado G et al.; The novel melampolides (11R)-11,13-dihydro-schkuhriolide (7), (11S)-11,13-dihydro-schkuhriolide (8), and schkuhrioidiol (11), along with the known constituents, frutescin (1), schkuhriolide (2), frutescinic acid (4), allo-schkuhriolide (5), and epoxyschkuhriolide (6) were isolated from the aerial parts of Schkuhria schkuhrioides . The structures of the new compounds were determined by spectroscopic methods . Compounds 1, 2, 4, 5, and 6 displayed no significant cytotoxic or antimicrobial activities. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi, 1994 May, 27(2), 70 - 9 Susceptibility of avian mycoplasmas isolated in Taiwan to 21 antimicrobial agents; Lin MY et al.; Twenty-one antimicrobial agents were incorporated individually into Frey's agar to evaluate their inhibitory activities against 86 isolates of avian mycoplasmas recently detected in Taiwan . Among them, 45 and 37 isolates were found positive with Mycoplasma gallisepticum and Mycoplasma synoviae fluorescent antibody conjugate, respectively . Twenty-one other isolates were unable to be identified by the above 2 conjugates . All of the field isolates were highly sensitive (with MIC50 < 1 microgram/ml) to enrofloxacin, gentamicin, myplabin, tiamutin and tylosin . However, those field isolates were highly resistant (with MIC50 > 32 micrograms/ml) to apramycin, chlortetracycline (CTC), erythromycin (ER), flumequine (FI), nalidixic acid (NA), oxolinic acid (OA), oxytetracycline (OTC) and spiramycin (SP) . The inhibitory activities of the antibiotics which possessed an MIC90 of 50 micrograms/ml or less against local isolates were, in decreasing order, enrofloxacin (< 0.004 microgram/ml), gentamicin (1.53 micrograms/ml), tiamutin (1.81 micrograms/ml), tylosin (3.2 micrograms/ml), streptomycin (SM; 12.0 micrograms/ml), colistin (13.1 micrograms/ml), chloramphenicol (14.0 micrograms/ml), spectinomycin (15.0 micrograms/ml), myplabin (16.0 micrograms/ml), spiramycin (30.0 micrograms/ml), minocycline (32.0 micrograms/ml) . The MIC90 of OA, CTC, SM, FI, SP, OTC, ER or NA was greater than 50 micrograms/ml; which work poorly in the control of mycoplasmoses . Since the antibiotic control policy is quite loose in Taiwan, many antimicrobial agents are often freely used in clinics, with a resulting gradual decrease in the inhibitory activity to the avian mycoplasmas. Anim Genet, 1998 Aug, 29(4), 283 - 9 Characterization of beta-defensin prepropeptide mRNA from chicken and turkey bone marrow; Brockus CW et al.; Four avian beta-defension prepropeptide cDNA sequences {gallinacins: Gal 1 (synonym CHP 1, chicken heterophil peptide 1), and Gal 2; turkey heterophil peptides: THP 1 and THP 2} were amplified from chicken or turkey bone marrow mRNA samples, respectively . Partial chicken beta-defensin cDNA sequences were obtained using degenerate primers based on chicken peptide sequences (Gal 1/CHP 1 and Gal 2) . The complete cDNA sequences of the chicken beta-defensins were then determined by designing specific intrapeptidal primers, from the newly acquired sequence, and pairing one primer with a specific poly A primer tail sequence (3' end) and the other primer with an adapter primer in a 5' rapid amplification of cDNA ends (RACE) reaction . The two, turkey beta-defensins were amplified from turkey marrow using primers designed from chicken beta-defensin preproregions . The complete amino acid sequences for the prepropeptides were deduced for all four avian beta-defensins . Previously, only partial mature peptide sequences for the turkey beta-defensins and complete mature peptide sequences for the chicken beta-defensins were known . All sequences obtained translated accurately to complete and partial amino acid sequences reported for beta-defensins purified from chicken and turkey heterophil granules except for one additional amino acid for Gal 1/CHP 1 . The four deduced beta-defensin proregions lack the long, negatively charged propiece reported in classical defensin proregions . These regions are thought to stabilize and inactivate the positively charged mature peptide and target the propeptide to the storage granule . Instead, these beta-defensin proregions are shorter and similar to storage granule-free beta-defensins proregions reported for bovine tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) . These are the first prepropeptide beta-defensins from leukocyte granules to be completely characterized. J Eval Clin Pract, 1998 Aug, 4(3), 191 - 5 Improving clinical outcome in bacteremia; Herchline T et al.; Bacteremia is associated with significant morbidity and mortality . There is wide variation in morbidity and mortality rates according to organism and predisposing conditions . Additionally, prompt administration of appropriate antimicrobial agents is associated with a decrease in mortality . Unfortunately, many bacteremic patients receive inappropriate or no antibiotics . Infectious disease consultation can decrease the number of patients receiving inappropriate initial therapy . 'Quality standard for the treatment of bacteremia' (Gross et al., 1994, Infection Control and Hospital Epidemiology 15, 189-192) is a consensus paper; its purpose is to 'improve the treatment of hospitalized patients with documented bacteremia by ensuring that they receive an antibiotic appropriate in light of the blood-culture susceptibility of the pathogen isolated.' A programme to assess the treatment of bacteremia can improve the quality of care with a modest commitment of additional resources . Many of the activities could be performed by a pharmacist, infection control practitioner, or pathologist . However, physician-to-physician communications are most likely to be successful . This programme should be considered a component of a hospital's quality-improvement programme; either the hospital quality assurance or infection control committee could be responsible for the programme . We encourage adoption of the standard, and recommend prospective monitoring to include the choice of empiric antimicrobial agents. Jpn J Antibiot, 1997 Jul, 50(7), 640 - 9 {Antimicrobial activities of roxithromycin against recently obtained clinical isolates}; Igari J et al.; The purpose of our investigation was to monitor current trends in the susceptibility patterns of clinical bacterial isolates to roxithromycin (RXM) . We measured the MICs of macrolide antibiotics, such as RXM, erythromycin (EM), clarithromycin (CAM), rokitamycin (RKM) and midecamycin (MDM), and other classes of antibacterial compounds against various clinical isolates at seven institutions between October and December in 1994 and 1995 . RXM had excellent antibacterial activities for S . pyogenes, S . agalactiae, M . (B.) catarrhalis and methicillin sensitive S . aureus . Against methicillin sensitive S . epidermidis, RXM activity was fairly good but about 20% of the strains had MIC > or = 128 micrograms/ml . The activity against S . pneumoniae was not so potent and similar to activities of EM, CAM, MDM, and clindamycin . The vast majority of methicillin resistant S . aureus and S . epidermidis were also resistant to macrolide antibiotics and other classes of compounds tested . In conclusion, RXM is an unique macrolide antibiotic by retaining potent activity against S . pyogenes, S . agalactiae, S . aureus except MRSA, M . (B.) catarrhalis and M . pneumoniae. Contraception, 1998 Jul, 58(1), 35 - 8 Dose-response effects of gramicidin-D, EDTA, and nonoxynol-9 on sperm motion parameters and acrosome status; Centola GM; Previous reports showed that gramicidin-D (G-D), a polypeptide with antiviral and antimicrobial properties, nonoxynol-9 (N9), a common spermicidal detergent, and EDTA, a Ca-Mg chelating agent, inhibited sperm motility and cervical mucus penetration . The purpose of this study was to determine the dose-response effects of G-D, N9, EDTA and G-D + EDTA on sperm motion parameters and acrosome status . Semen specimens from known fertile donors were subjected to computer-assisted semen analysis of motility, path velocity, progressive velocity, and hyperactivation prior to and after incubation with varying concentrations of gramicidin-D, EDTA and nonoxynol-9 . Each specimen was also prepared for acrosome status using rhodamine isothiocyanate conjugated pisum sativum agglutinin (RITC-PSA) . There was a significant decrease in motility by G-D, EDTA, G-D + EDTA, and N9 at all doses as compared to the fresh specimen . N9 completely immobilized all sperm at each dose . Progressive velocity and path velocity also decreased in a dose-response manner . Sperm hyperactive motility also significantly decreased in all groups . The majority of sperm remained acrosome intact following exposure to all doses tested, whereas N9 resulted in complete breakdown/release of the acrosomal contents . This study confirms previous reports that G-D, EDTA, and N9 significantly impair sperm motility and motion parameters . The effective 100% inhibitory concentration was seen only with N9, whereas G-D, EDTA, and G-D + EDTA resulted in incomplete impairment of sperm motion parameters . At the concentrations used, N9 demonstrated potent spermostatic activity . Gramicidin-D and EDTA should be further studied for their potential contraceptive spermostatic activityPIP: Gramicidin-D (G-D), a polypeptide with antiviral and antimicrobial properties, the spermicidal detergent nonoxynol-9 (N-9), and the Ca-Mg chelating agent EDTA have been shown in previous studies to inhibit sperm motility and cervical mucus penetration . This study utilized computer-assisted methods to investigate the dose-response effects of incubation with G-D, N-9, EDTA, and G-D plus EDTA on sperm motion parameters and acrosome status . Semen specimens were acquired within 30 minutes of ejaculation from six fertile US sperm donors . Compared to the fresh (untreated) specimen, there was a significant decrease in sperm motility produced by G-D, EDTA, G-D plus EDTA, and N-9 at all doses . Progressive and path velocity and sperm hyperactive motility also decreased in a dose-response manner in all groups . However, sperm immobilization was complete at the concentrations used only with N-9 . The majority of sperm remained acrosome-intact after exposure to all tested doses of G-D and EDTA, but N-9 resulted in complete breakdown and release of the acrosomal contents . A combination of N-9 and G-D or N-9 and EDTA at lower doses might produce the desired inhibition of sperm motility without toxicity and this possibility should be investigated . At the present time, however, G-D or EDTA, alone or in combination, cannot be considered effective contraceptive agents . South Med J, 1998 Sep, 91(9), 861 - 3 Blastomycosis as an etiology of acute lung injury; Thompson CA et al.; Blastomyces dermatitidis, a dimorphic broad-based budding yeast endemic to the Mississippi River Valley region, is responsible for morbidity in humans via inhalation and dissemination . The response of acute lung injury, which produces an illness with serious morbidity and an approximately 50% mortality, uncommonly occurs . Diagnosis can be difficult, and a high index of suspicion should be maintained in endemic regions for patients with acute lung injury of uncertain etiology, especially if their condition deteriorates on broad-spectrum antimicrobial and antitubercular therapy and they have a previous insidious respiratory complaint and constitutional symptoms . Diagnosis should be aggressively pursued and treatment with amphotericin B (0.6 to 0.8 mg/kg/day) initiated as early as possible. Postgrad Med, 1998 Sep, 104(3), 93 - 9, 103-4 What role for antibiotics in otitis media and sinusitis? Ahuja GS, Thompson J. In patients with otitis media or sinusitis, antibiotics must be used judiciously . First-line treatment for both uncomplicated acute otitis media and acute sinusitis is amoxicillin . Erythromycin ethylsuccinate and sulfisoxazole or TMP-SMZ may be used in patients who are allergic to penicillin . Beta-lactamase-stable agents should be given when no response occurs within 48 to 72 hours . In cases in which penicillin-resistant pneumococcus is suspected, high-dose amoxicillin, with or without clavulanate, or clindamycin should be considered . Antibiotics are not indicated for initial treatment of otitis media with effusion but may be considered for effusions lasting longer than 3 months . Prophylactic antibiotics should be considered only for recurrent acute infections occurring three or more times within 6 months or four or more times within a year . The common cold should not be treated with antibiotics, and antimicrobial therapy should be initiated only when there is reasonable clinical certainty about the presence of acute sinusitis. Vet Clin North Am Equine Pract, 1998 Aug, 14(2), 291 - 307 Pathophysiology of acquired dental diseases of the horse; Crabill MR et al.; Periodontitis, infundibular necrosis, and periapical infection are dental diseases commonly affecting adult horses . Routine dental examinations and care may help to prevent these diseases . Further investigation of the treatment of horses with these diseases using local antimicrobial therapy, restorative dentistry, and endodontic therapy is needed . An understanding of the pathogenesis of these diseases aids in diagnosis and treatment . Gingival hyperplasia and odontogenic tumors are uncommon but should remain in a list of differential diagnoses when examining a horse with pertinent clinical signs . Recognition of odontogenic tumors as early as possible may facilitate surgery . Examination of the oral cavity of foals beyond the neonatal period should allow identification of brachygnathia and timely treatment when indicated. J Control Release, 1998 Jun, 54(1), 29 - 37 Pharmacodynamic and pharmacokinetic rationales for the development of an oral controlled-release amoxicillin dosage form; Hoffman A et al.; The goal of this investigation was to develop an oral sustained-release formulation for amoxicillin that would maximize the duration of active drug concentration in the extracellular fluid, thus increasing the dosing interval while assuring antimicrobial activity . This rationale is based on the pharmacodynamic properties of the drug which is non- concentration dependent on the one hand, while requiring long exposure of the pathogen to the drug with minimal post-antibiotic effect on the other . Due to pharmacokinetic constraints, including short biological half-life and limited 'absorption window' (confined to the small intestine) with poor colonic absorption, the new matrix tablet formulation, composed of hydrophilic (hydroxypropyl methyl-cellulose) polymer, was designed to release 50% of its contents within the first 3 h and to complete the drug release process over 8 h (under in vitro conditions) . The pharmacokinetics of the new formulation was evaluated in 12 healthy volunteers and compared to a conventional gelatin capsule with both formulations containing 500 mg amoxicillin . The plasma concentrations of active amoxicillin and penicilloic acid were determined by an HPLC method with a fluorometric detector . It was found that the area under the concentration-time curve and maximal serum amoxicillin concentrations following the sustained release preparation were lower than the immediate release formulation . However, the time over the required threshold concentrations, i.e . the minimal inhibitory concentration (MIC) as well as the more clinically relevant parameter--four times MIC of the drug against susceptible pathogens, was found to be maintained for significantly longer periods . The results suggest that in order to achieve a twice daily dosing regimen that will provide therapeutic concentrations for the whole 12 h dosing intervals, a larger dose of the new formulation should be given (e.g . 750 mg or even 1 g twice daily) . This recommendation is based on the large interindividual differences of the extent of amoxicillin absorption found in this investigation, and is intended to assure that the 'poor' absorbers will also benefit from full antibiotic efficacy . This dosing regimen will lead to increased patient compliance and improved therapeutic outcome. J Ethnopharmacol, 1998 Sep, 62(2), 183 - 93 Screening of some Indian medicinal plants for their antimicrobial properties; Ahmad I et al.; A total of 82 Indian medicinal plants traditionally used in medicines were subjected to preliminary antibacterial screening against several pathogenic and opportunistic microorganisms . Aqueous, hexane and alcoholic extracts of each plant were tested for their antibacterial activity using agar well diffusion method at sample concentration of 200 mg/ml . The results indicated that out of 82 plants, 56 exhibited antibacterial activity against one or more test pathogens . Interestingly, extracts of five plants showed strong and broad spectrum activity as compared to rest of 51 plant extracts which demonstrated moderate activity . On the whole the alcoholic extracts showed greater activity than their corresponding aqueous and hexane extracts . Among various extracts, only alcoholic extracts of Emblica officinalis, Terminalia chebula, Terminalia belerica, Plumbago zeylanica and Holarrhena antidysenterica were found to show potentially interesting activity against test bacteria . These active crude alcoholic extracts were also assayed for cellular toxicity to fresh sheep erythrocytes and found to have no cellular toxicity. Control Clin Trials, 1998 Oct, 19(5), 499 - 514 Design of the PID Evaluation and Clinical Health (PEACH) Study; Ness RB et al.; This paper describes the PID Evaluation and Clinical Health Study (PEACH), a multicenter, randomized clinical trial designed to compare treatment with outpatient and inpatient antimicrobial regimens among women with pelvic inflammatory disease (PID) . PEACH is the first trial to evaluate the effectiveness and cost-effectiveness of currently recommended antibiotic combinations in preventing infertility, ectopic pregnancy, chronic pelvic pain, recurrent PID, and other health outcomes . It is also the largest prospective study of PID ever conducted in North America . We describe the PEACH study's specific aims, study organization, patient selection criteria, conditions for exclusion, data collected upon entry, randomization and treatment, adherence measures, follow-up activities, quality-of-life measures, outcomes, and statistical analyses . In the first 11 months of enrollment (March 1996-January 1997), 312 women were randomized . Of eligible women, 59% consented to enroll . Participating women are primarily black (72%) and young (mean age 24 years) . After a median of 5.5 months of follow-up, we were in contact with 95% of study participants . The PEACH study will provide a rationale for selecting between inpatient and outpatient antibiotic treatment, the two most common treatment strategies, for PID. Pharmazie, 1998 Aug, 53(8), 543 - 7 Pyridines and pyrazolines from salicylic acid derivatives with propenone residue and their antimicrobial properties; Grant N et al.; Reaction of the propenones 1c, d with chlorosulfonyl isocyanate followed by hydrolysis gave the corresponding carbamoyloxybenzoates 2a, b . While their reaction with ethyl isocyanate afforded the 1,3-benzoxazine-2,4-diones 3a, b . Reaction of 1a, b with aryl hydrazines gave the pyrazolines 4a, d, whereas, with hydrazine hydrate in acetic acid, the acetyl derivatives 4e, f were produced . 1c, d reacted with malononitrile and ethyl cyanoacetate affording the cyanopyridines 5 and cyanopyridones 6 respectively . The products show antimicrobial activities. Nahrung, 1998 Aug, 42(3-4), 187 - 93 On the novel catalytically-independent antimicrobial function of hen egg-white lysozyme: a conformation-dependent activity; Ibrahim HR; Dependency of the antimicrobial activity on the conformation of lysozme was examined by the means of gradual thermal inactivation at neutral pH and different temperatures . We found that heating of lysozyme at increasing temperatures for 20 min in pH 6.0 results in progressive loss of enzyme activity, while greatly promotes its antimicrobial action to the Gram-negative bacteria without a detrimental effect on the inherent bactericidal activity to Gram-positive ones, suggesting action independent of catalytic function . The most potent bactericidal conformation of lysozyme to either Gram-negative or -positie bacteria was that retaining approximately 50% of the native enzyme activity (HL80/6) . HL80/6 showed several fold increase in surface hydrophobicity, with exposed two thiol groups, and 17% deamidation . Spectrophotometric analysis of HL80/6 revealed slight changes in its secondary structures, but considerable global conformational changes as a result of the formation of beta conformation, via cyclic imide, at the three aspartylglycyl sequences of lysozyme molecule . Direct damage to the bacertial membranes by HL80/6, was demonstrated by using ELISA and liposomal membrane model . Furthermore, the antimicrobial activity of HL80/6 was inhibited by the divalent cations Ca2+ and Mg2+ suggesting that HL80/6 interacts at a divalent cation binding site on the bacterial membrane and subsequently permeabilize it . The results introduce an interesting structure-antimicrobial relationship that the antimicrobial action of lysozyme is independent of its catalytic function . In addition, it is worth emphasizing that the naturally-occurring conformational transition of lysozyme at physiological temperatures can be a biologically relevant event to switch its antimicrobial specificity to include the food-borne pathogens and heralding fascinating opportunities for application in formulated food systems. Semin Perinatol, 1998 Aug, 22(4), 260 - 6 Cytomegalovirus infection; Brown HL et al.; Cytomegalovirus (CMV) infection is the most common perinatal infection and may result in severe injury to the fetus . Forty percent to 50% of infants delivered to mothers with primary CMV will have congenital infections . Of these, 5% to 18% will be overtly symptomatic at birth . The mortality rate in these children is almost 30%; approximately 80% of the survivors have severe neurological morbidity . The majority of congenitally infected infants will be asymptomatic at birth; 10% to 15% of these children subsequently have sequelae such as visual and auditory defects . If recurrent or reactivated CMV infection develops during pregnancy, the risk of serious fetal injury is very low . Similarly, neonatal infection acquired during delivery or from breast feeding also poses minimal risk to the child . Because antimicrobial therapy and immunoprophylaxis for CMV infection are unsatisfactory, pregnant women must be educated about preventive measures. J Antimicrob Chemother, 1998 Aug, 42(2), 241 - 3 Diethylcarbamazine-related antimicrobial activity in Mycobacterium tuberculosis-infected blood; Kitchen LW et al.; Previous studies have suggested that diethylcarbamazine (DEC), a drug used for filariasis control, may be useful in the treatment of mycobacterial infections . In this experiment, Mycobacterium tuberculosis was added to blood samples from two groups (healthy and diabetic) of adult non-smoking donors . Portions of each sample were tested with and without DEC at clinically achievable levels . Statistically significant DEC-related percentage decreases in BACTEC growth index counts were noted for each group (Wilcoxon one-sample signed-rank tests, alpha = 0.05, two-tailed) . These results suggest that administration of DEC for filariasis control could have a positive impact on tuberculosis control. Pediatrics, 1998 Sep, 102(3 Pt 1), 546 - 53 Comparative Efficacy of the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine and Lederle whole-cell component DTP vaccine in German children after household exposure . Pertussis Vaccine Study Group; Heininger U et al.; BACKGROUND: A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany . DESIGN: Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY) . An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age . Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period . RESULTS: During a 3.5-year study period, 10271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses . Depending on the case definition, 160 to 519 household exposures to pertussis were identified . In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis . Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of greater than or equal to 7 days duration caused by Bordetella pertussis was 84% (95% confidence interval {CI} = 65-93) and that of DTaP was 58% (95% CI = 30-75) . Using similar criteria, the efficacy against typical pertussis (greater than or equal to 21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95% CI = 77-99) and 86% (95% CI = 62-95) for DTP and DTaP, respectively . The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32-69) and 38% (95% CI = 13-56) for DTP and DTaP, respectively . CONCLUSION: This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy . Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness . When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines. Rev Clin Esp, 1998 Jul, 198(7), 420 - 3 {Microbiologic diagnosis of Helicobacter pylori and its resistance to antibiotics}; Lopez Bartolome O et al.; From March 1995 to February 1996 a total of 386 gastroduodenal biopsies were processed for microbiological diagnosis of Helicobacter pylori which included culture, Gram staining and urease test . For susceptibility studies to five antimicrobial agents, 35 additional gastroduodenal biopsies (n = 421) were added . There were 272 (70.4%) positive cultures, 220 (56.9%) samples with positive urase test and 244 (63.2%) with positive result in Gram-staining; both tests were statistically significant compared with culture (p < 0.05) . Considering culture as the reference method, sensitivity and specificity values for the urease test were 77.0% and 92.1% and for Gram staining 86.7% and 92.9%, respectively . A total of 11 isolates were recovered from the 35 biopsies processed only for culture . Susceptibility testing of 283 isolates (272 + 11) was performed to the following antimicrobials: amoxicillin, metronidazole, clarithromycin, azythromycin and tetracycline . Resistance to metronidazole was 25.4% and the corresponding values for clarithromycin and azithromycin 9.5% . No resistance to amoxicillin or tetracycline was observed . Urease test and Gram staining are two easy-to-perform tests and when taken together allow the microbiological diagnosis of Helicobacter pylori infection . Culture should be performed to know the evolution of resistance to antimicrobials used for treatment of this infection. J Can Dent Assoc, 1998 Jul-Aug, 64(7), 496 - 502 Antimicrobial resistance: dentistry's role; Haas DA et al.; The resistance of bacteria, fungi and viruses to antimicrobials is increasing rapidly, with deleterious consequences . Dentistry's role in this development is unclear, because the necessary information has not yet been collected . Nevertheless, dentists should recognize that it is essential to use antimicrobials in an appropriate and responsible manner, both to treat infection effectively, and to minimize the likelihood that the bacteria in the general population will develop resistance to antimicrobials . The purpose of this article is to make dentists aware of the concerns raised by antimicrobial resistance, and how it can be avoided. Curr Opin Chem Biol, 1998 Aug, 2(4), 529 - 34 Novel approaches to the discovery of antimicrobial agents; Schmid MB; With the completion of numerous bacterial genome sequences, the discovery of antibacterial drugs has fully entered the genomic era . The strategies for effectively using genomic information for target identification, target characterization, screen development and compound evaluation are emerging, and have greatly increased the number of antibacterial targets available for screening . Fortunately, simultaneous efforts in improving miniaturization, robotics and database tools are underway so that the potential of genomics can be realized. Proc Natl Acad Sci U S A, 1998 Sep 15, 95(19), 11342 - 7 Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study; Uttenweiler-Joseph S et al.; We have developed an approach based on a differential mass spectrometric analysis to detect molecules induced during the immune response of Drosophila, regardless of their biological activities . For this, we have applied directly matrix-assisted laser desorption/ionization MS to hemolymph samples from individual flies before and after an immune challenge . This method provided precise information on the molecular masses of immune-induced molecules and allowed the detection, in the molecular range of 1.5-11 kDa, of 24 Drosophila immune-induced molecules (DIMs) . These molecules are all peptides, and four correspond to already characterized antimicrobial peptides . We have further analyzed the induction of the various peptides by immune challenge in wild-type flies and in mutants with a compromised antimicrobial response . We also describe a methodology combining matrix-assisted laser desorption ionization time-of-flight MS, HPLC, and Edman degradation, which yielded the peptide sequence of three of the DIMs . Finally, molecular cloning and Northern blot analyses revealed that one of the DIMs is produced as a prepropeptide and is inducible on a bacterial challenge. Antimicrob Agents Chemother, 1998 Sep, 42(9), 2160 - 70 Inhibitory action of a truncated derivative of the amphibian skin peptide dermaseptin s3 on Saccharomyces cerevisiae; Coote PJ et al.; The inhibitory activity of a truncated derivative of the natural amphibian skin peptide dermaseptin s3-(1-16)-NH2 {DS s3 (1-16)} against Saccharomyces cerevisiae was studied . Significant growth inhibition was observed after exposure to 3.45 microgram of the peptide per ml at pH 6.0 and 7.0, with complete growth inhibition occurring at 8.63 microgram of peptide per ml for all pH values tested . Using confocal scanning laser microscopy, we have shown that DS s3 (1-16) disrupted the yeast cell membrane resulting in the gross permeabilization of the cell to the nuclear stain ethidium bromide . However, the principal inhibitory action of the peptide was not due to disruption of intracellular pH homeostasis . Instead, growth inhibition by the peptide correlated with the efflux of important cellular constituents such as ADP, ATP, RNA, and DNA into the surrounding medium . The combination of DS s3 (1-16) with mild heating temperatures as low as 35 degreesC significantly enhanced the inhibitory effect of the peptide (8.63 microgram/ml), and at 45 degreesC greater than 99% of the population was killed in 10 min . In summary, a derivative of a natural antimicrobial peptide has potential, either alone or in combination with mild heating, to prevent the growth of or kill spoilage yeast. Am J Vet Res, 1998 Sep, 59(9), 1096 - 100 Detection of milk antibiotic residues by use of screening tests and liquid chromatography after intramammary administration of amoxicillin or penicillin G in cows with clinical mastitis; Anderson KL et al.; OBJECTIVE: To compare results of 6 commercially available milk antimicrobial screening tests with results of liquid chromatography (LC) when testing milk samples from individual cows treated for mild clinical mastitis by intramammary (IMM) infusion with amoxicillin or penicillin G . ANIMALS: 6 cows with noninduced clinical mastitis: 3 treated by IMM infusion with amoxicillin and 3 treated by IMM infusion with penicillin G . PROCEDURE: Composite milk samples were collected before, during, and after treatment . Samples were assayed by use of the screening tests and their results and those of LC were compared . The LC results were assumed to represent the true result . RESULTS: Results of screening tests compared well with results of LC, with agreement of 94% . Positive screening test results for samples containing drug values below the established tolerance or safe level, as evaluated by LC, were obtained from 2 cows in which abnormal milk, as well as marked increases in composite milk somatic cell count, were observed . With the exception of 1 test in 1 cow, all screening tests had negative results at the end of the labeled milk-withholding time . CONCLUSIONS AND CLINICAL IMPLICATIONS: On the basis of results of the limited sample reported, the screening tests appeared to provide good agreement overall, compared with LC results, when testing milk of individual cows treated by IMM infusion with amoxicillin or penicillin G . Positive screening test results for milk samples containing amoxicillin or penicillin G at values below the established tolerance or safe level, as evaluated by LC, may occasionally be obtained. Surg Neurol, 1998 Sep, 50(3), 208 - 12 Topical irrigation with polymyxin and bacitracin for spinal surgery; Savitz SI et al.; BACKGROUND: The purpose of the present study was to evaluate constant irrigation with saline containing 50,000 units each of polymyxin and bacitracin in a regimen of antimicrobial prophylaxis for clean spinal surgery at two community hospitals with a zero infection rate . METHODS: The focus was on the bactericidal effects of prophylactic topical antibiotics by assessing random contamination in neurosurgical wounds from: 1) the flora of the integument and nares of the operating team, 2) the surgical apparel, 3) the patient's skin, 4) air-borne organisms in the operating theater, and 5) the surgeon's gloves . RESULTS: Based on individual biotyping of bacteria and antimicrobial sensitivity testing, no consistent source or pattern could be uncovered for the organisms recovered from the operative site . Relying on longitudinal data, the incidence of intraoperative bacterial growth with continuous saline lavage was reduced from 64 to 4% when the combination of topical polymyxin and bacitracin was added . CONCLUSIONS: Although the virtual elimination of bacterial growth in the surgical site was accomplished, the efficacy of topical antibiotics in the prevention of wound infection remains unproven. Curr Opin Chem Biol, 1997 Aug, 1(2), 162 - 8 Combinatorial approaches to polyketide biosynthesis; Leadlay PF; Polyketides are a large and structurally diverse family of natural products based on chains of carboxylic acid units . The polyketide synthases that make aromatic polyketides have already been used to generate small combinatorial libraries, by expressing individual genes from different biosynthetic pathways together, so that the enzymes they encode can interact to make novel products . Recent work has shown how to choose these individual components to increase the chances of obtaining such hybrid aromatic compounds . In other polyketide synthases which synthesise complex reduced polyketides, the constituent enzymes are actually linked as domains in a giant multienzyme complex along which the growing polyketide chain is passed . A combinatorial approach here therefore requires the fusing together of individual enzymatic domains from several such synthases in as many productive ways as can be devised, so that the enzyme assembly line produces a library of altered products . A key recent advance has been to demonstrate that such genuinely hybrid enzymes do work as predicted, for example a broad-specificity enzyme that recruits the chain starter unit for an antiparasitic compound has been grafted onto a synthase that makes antimicrobial macrolides. J Rheumatol, 1998 Sep, 25(9), 1807 - 12 Chemically modified non-antimicrobial tetracyclines inhibit activity of phospholipases A2; Pruzanski W et al.; OBJECTIVE: Tetracyclines have been recognized as useful agents for therapy of inflammatory arthritides . However, prolonged use of tetracyclines is limited by their detrimental antimicrobial properties . Recently, a group of chemically modified tetracyclines (CMT) devoid of antimicrobial properties has been synthesized . Some CMT were found to inhibit various matrix metalloproteinases (MMP) . We reported previously that antimicrobial tetracyclines inhibit the activity of proinflammatory secretory group II phospholipase A2 (sPLA2) . The objective of this study was to detect whether non-antimicrobial CMT also inhibit sPLA2 and other phospholipases A2 . METHODS: Ten synthetic CMT were tested for inhibition of sPLA2 human and porcine PLA2, and Naja naja PLA2 . PLA2 activity was assessed by radiolabeled Escherichia coli assay using standard and high calcium concentrations . RESULTS: Six of 10 CMT inhibited sPLA2 activity at concentrations close to or lower than 50 microg/ml . All 6 CMT had identical C1-3 and C10-12a positions in the 4-ringed nucleus of the tetracycline molecule . Calcium concentrations up to 20 mM did not eliminate the inhibitory activity of CMT . Inhibition of other PLA2 was induced by some CMT, all but one (CMT-9) belonging to the group of strong inhibitors of sPLA2 . Thus, inhibition of PLA2 different from sPLA2 does not necessarily require identical C1-3/C10-12a residues . CONCLUSION: Since CMT, which inhibit proinflammatory sPLA2, are also inhibitors of some MMP, they may be useful for therapy of inflammatory diseases in which both MMP and sPLA2 are overexpressed. Cell Biol Toxicol, 1998 Aug, 14(4), 283 - 92 In vitro study of cytotoxicity of quinolones on rabbit tenocytes; Bernard-Beaubois K et al.; Tendinitis and tendon rupture complicating fluoroquinolone therapy have been reported recently, especially affecting men over 60 years . These new quinolones are more potent antimicrobial agents than older nonfluorinated compounds like nalidixic acid . We compared the effects of one quinolone (nalidixic acid) and two fluoroquinolones (norfloxacin and pefloxacin) on cultured rabbit Achilles tendon cells . First, we examined their effects on cell viability, mitochondrial succinate dehydrogenase and global activity, mitochondrial activity using microtitration methods . Pefloxacin and norfloxacin were more cytotoxic than nalidixic acid according to IC50 values . These results confirm that mitochondria represent a biological target of fluoroquinolones . Moreover, the extracellular matrix was studied by molecular hybridization . After a 72 h treatment, the level of type I collagen transcripts was not modified with any of the three antimicrobial agents, whereas mRNA encoding decorin was decreased with 10(-4) mol/L pefloxacin only . The decrease of transcripts encoding decorin suggests that this matrix component is another target of pefloxacin and modification of decorin seems to be an early event (before mitochondrion alteration) which may contribute to the explanation of tendon rupture. Poult Sci, 1998 Sep, 77(9), 1306 - 11 Effect of tylosin tartrate (Tylan Soluble) on cellular immune responses in chickens; Baba T et al.; Although many antimicrobial agents have been reported to cause immunosuppression in animals, macrolide antibiotics enhance immune function . Tylosin is a macrolide antibiotic approved for the control of mycoplasmosis in poultry . The purpose of this investigation was to determine the effect of tylosin on cellular immune functions in chickens . There was no significant difference in adherent splenocyte chemotaxis between tylosin-treated and untreated (control) chickens . Tylosin increased splenocyte proliferation and splenocyte conditioned medium (CM) proliferative activity above control levels . Removal of adherent splenocytes before preparation of CM caused a reduction in CM proliferative activity . Tylosin also increased antitumor activity of splenocytes . These data are the first to suggest that the macrolide antibiotic, tylosin tartrate, has a modulatory effect in chickens on the immune parameters studied. Am J Gastroenterol, 1998 Sep, 93(9), 1432 - 5 Clarithromycin-resistant Helicobacter pylori in patients with duodenal ulcer in the United States; Vakil N et al.; BACKGROUND: Clarithromycin is a key component of several antimicrobial treatment regimens for Helicobacter pylori . Cure rates with clarithromycin-containing regimens are significantly decreased when resistance is present . Resistance develops by a point mutation in the ribosomal RNA of some organisms exposed to clarithromycin . We studied the prevalence of clarithromycin-resistant organisms in patients with duodenal ulcer in the United States from 1993-96 . METHODS: Patients with endoscopic evidence of a duodenal ulcer were studied . Gastric biopsies were cultured for H . pylori and antimicrobial sensitivity was determined by the E-test (epsilometer agar diffusion gradient) . RESULTS: In 1993-94, three of 78 patients (4%) had clarithromycin-resistant strains of H . pylori . In 1995-96, 44 of 348 patients (12.6%; p = 0.025) had resistant strains of H . pylori . Patients who had previously failed antimicrobial treatment for H . pylori accounted for much of the increase in resistant strains (25%) . CONCLUSIONS: Failed therapy with clarithromycin-based regimens is a growing cause of antimicrobial resistance in H . pylori in the United States . Whereas the overall rates of primary resistance are low, the increase in secondary resistance over a short period of time is worrisome . New treatments that prevent the emergence of resistance may be important in the future. Chemotherapy, 1998 Sep-Oct, 44(5), 355 - 63 Antimicrobial prophylaxis in laparoscopic and conventional cholecystectomy . Conclusions of a large prospective multicenter quality assurance study in Germany; Lippert H et al.; BACKGROUND: Postoperative infection following cholecystectomy poses a significant threat to recovery, with major cost repercussions . Though antimicrobial prophylaxis is commonly practiced, its value - particularly in laparoscopic cholecystectomy - has not yet been adequately documented . METHOD: In a prospective multicenter quality assurance study in 28 German hospitals, an analysis of data collected on 4,477 patients undergoing conventional (n = 1,349) or laparoscopic (n = 3,128) cholecystectomy was performed; 2,217 patients received and 2,260 did not obtain perioperative antibiotic cover . RESULTS: Postoperative infections occurred in a total of 136 patients, with infection rates of 5.0% in those without prophylaxis, 0.8% in those on ceftriaxone, and 1.2% in those on other antibiotic regimens . Patients receiving prophylaxis fared significantly better than those with no prophylaxis in terms of the rate of postoperative wound infections, chest infections, other complications, reoperation and mortality . CONCLUSION: Neither laparoscopic nor conventional open cholecystectomy should be performed without adequate perioperative antimicrobial prophylaxis in future, especially since such measures also reduce hospital stay and hence the costs. Helicobacter, 1998 Sep, 3(3), 206 - 11 Cure of H . pylori infection using a 7-day triple therapy combining pantoprazole with two antibiotics; Adamek RJ et al.; BACKGROUND: Acid pump inhibitors combined with antimicrobials cure gastritis and peptic ulcer disease but a standard therapy has not yet been established . We therefore investigated a triple therapy with pantoprazole . METHODS: The aim of this open-label monocenter trial, involving 30 intention-to-treat patients with peptic ulcer disease or functional dyspepsia, was to assess the H . pylori cure rate after a 7-day triple therapy with pantoprazole (40 mg bid) plus metronidazole (500 mg bid) and amoxicillin (1 g bid) . The H . pylori status was assessed by rapid urease test, histological examination and culture at the initial examination and by histological examination and culture at the study end 4 weeks after ending all therapy . RESULTS: At the end of the trial H . pylori was eradicated in 21 of 27 per protocol patients (78%; 95% CI 58-91%) and in 21 of 30 patients included in the trial (70%; 95% CI 51-85%) . In 15 of 16 per protocol patients with metronidazole-sensitive strain (94%; 95% CI 70-100%) the infection was cured, but in contrast eradication was accomplished in only one of 3 patients with a metronidazole-resistant H . pylori strain . Post-treatment resistance to metronidazole was observed in 6 cases, although 4 of them had had H . pylori strains sensitive to metronidazole at the initial visit . The gastritis had clearly been improved, and the activity of gastritis had completely disappeared 4 weeks after treatment . Seven adverse events were observed in 7 patients, the intensity of which was moderate in 6 cases . CONCLUSIONS: This short-term triple therapy with pantoprazole, amoxicillin and metronidazole provides an effective regimen especially in patients with metronidazole-sensitive strain. Helicobacter, 1998 Sep, 3(3), 163 - 9 Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by "proteome" technologies; McAtee CP et al.; BACKGROUND: There is great interest in characterizing the proteins of the gastric pathogen, Helicobacter pylori, especially those proteins to which humans respond immunologically . Such proteins have potential importance in diagnosis and vaccine development . METHODS: Two-dimensional gel electrophoresis in combination with Western blotting was used to separate and identify potential antigens of Helicobacter pylori strain Z-170 . Proteins found to be reactive with pooled sera from 14 infected patients were individually digested in situ with endoproteinase Lys-C, and the resulting fragments were analyzed by matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) . RESULTS: Over 20 proteins were reactive in Western blots with pooled sera from 14 infected patients . The mass spectral data was compared with predictions from the H . pylori genome DNA sequence . Each of the 20 proteins was readily identified . CONCLUSIONS: We propose that this "proteome" approach for identification of previously unknown proteins will be useful in examining regulation of H . pylori gene expression and protein localization in the development of improved serologic tests to detect and monitor H . pylori infection . This approach will also be useful for identifying potential targets for antimicrobial or vaccine development for H . pylori and other pathogens whose genomes have been sequenced. J Vet Pharmacol Ther, 1998 Aug, 21(4), 274 - 81 Antibiotic effects on cytochromes P450 content and mixed-function oxygenase (MFO) activities in the American alligator, Alligator mississippiensis; Mayeaux MH et al.; There are no Food and Drug Administration (FDA)-approved antimicrobial agents for use in cultured American alligators (Alligator mississippiensis) destined for human consumption yet some producers administer antibiotics for prophylaxis . The cytochromes P450-dependent mixed-function oxygenases (MFO) catalyze the oxidation of xenobiotic compounds such as drugs, pesticides and polycyclic aromatic hydrocarbons . Herein, we describe the effects of oxytetracycline, ceftazidime and enrofloxacin on the MFO system of the American alligator, Alligator mississippiensis . Juvenile alligators (4 animals/treatment) were administered these antibiotics intraperitoneally in an effort to induce hepatic microsomal cytochromes P450 . Alligators treated with enrofloxacin exhibited emesis and convulsive spasms within 5 min of the initial injection . Total hepatic cytochromes P450 contents were significantly decreased in oxytetracycline-and enrofloxacin-pretreated alligators . In vitro hepatic microsomal benzyloxyresorufin O-dealkylase (BROD) activity was significantly decreased by enrofloxacin pretreatment . Western blots of proteins from antibiotic-pretreated alligator hepatic microsomes incubated with several mammalian and fish cytochromes P450 (CYP) antibodies exhibited little or no induction of CYP1A1, 2B, 2C and 2E1 . In vitro incubation with enrofloxacin and oxytetracycline caused a concentration-dependent decrease in alkyl-substituted phenoxazone dealkylase activities catalyzed by phenobarbital- and 3-methylcholanthrene-induced alligator hepatic microsomes. Biochem Biophys Res Commun, 1998 Aug 28, 249(3), 943 - 7 Identification of human beta-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia; Hiratsuka T et al.; Human beta-defensin-2 (hBD-2), a novel antimicrobial peptide, was originally isolated from human skin . We found that synthetic hBD-2 has high bactericidal activity against Escherichia coli under conditions nearly the same as in human bronchial airway surface liquid . We prepared an antiserum against hBD-2 and established a highly sensitive radioimmunoassay (RIA) . Reverse-phase high-performance liquid chromatography coupled with the RIA showed that hBD-2 in patients with human lung, bronchoalveolar lavage flid, and plasma . The plasma concentration of hBD-2 in patients with bacterial pneumonia was 32.1 +/- 3.7 fmol/ml (mean +/- SE), 3.9-fold that of normal individuals . By reverse transcription-polymerase chain reaction, the hBD-2 gene transcript was detected in the respiratory epithelial surface of human lung . Human beta-defensin-2 seems to function in airway mucosal defense . Our findings provide a clue to elucidate its pathophysiological significance in respiratory infection. Am J Respir Cell Mol Biol, 1998 Sep, 19(3), 352 - 6 Antibacterial peptides in bronchoalveolar lavage fluid; Schnapp D et al.; Defensins and other antimicrobial peptides act in the innate host defense of epithelial surfaces . Human beta defensin 1 (hBD-1) has recently been shown to be expressed in airway epithelial cells and so has been implicated as a primary component of antibacterial activity in human lung . We attempted to purify these molecules from bronchoalveolar lavage fluid (BALF) . Extraction of BALF on SepPak C-18 cartridges, followed by continuous acid-urea polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography yielded one fraction with antibacterial activity associated with factors of < 6.5 kD . N-terminal amino acid sequencing identified these peptides as human neutrophil defensins (HD) 1 through 3 . No hBD-1 was detected . Together with lysozyme, it appears that HD-1 through -3 are the most prominent antimicrobial factors in BALF . The contribution of epithelial defensins such as hBD-1 to antibacterial defense of human airway in vivo remains to be elucidated. J Reprod Immunol, 1998 Jul, 38(2), 155 - 67 The in vitro antimicrobial capacity of human colostrum against Chlamydia trachomatis; Ramsey KH et al.; We sought to assess the antimicrobial capacity of human colostrum against Chlamydia trachomatis . a common agent of ophthalmia neonatorum . Colostrum was collected from 13 post-partum females and tested in an in vitro assay of chlamydial growth inhibition using HeLa 229 cells as the host cell line . All samples significantly inhibited chlamydial growth in a dose-response manner . The percent inhibition ranged from 45.3 to 99.0 (mean=88.1+/-4.1) . The chlamydial growth inhibition activity of colostrum was found to be: heat- and freezing-resistant: more concentrated in colostrum than breast milk; was not attributable to interferon or antibody activity; and, could not be attributed to host cell cytotoxicity . Additionally, chlamydial growth inhibition occurred in < or = 15 min and was effective only when colostrum was incubated with chlamydiae prior to addition to HeLa 229 monolayers . Lastly, centrifugal fractionation of the colostrum yielded similar activity in the lipid pellicle and in the lipid-free supernatant . These results indicate that topically applied colostrum may have efficacy in the prophylaxis of ophthalmia neonatorum of chlamydial etiology in the absence of conventional modalities.
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