Bactericidal

J Antimicrob Chemother, 1996 Dec, 38(6), 1097 - 101
Trends in-original research published from the United Kingdom in the antimicrobial chemotherapy literature, 1980-1994; Williams AR et al.; There is a feeling that the contribution of researchers from the United Kingdom in the antimicrobial chemotherapy area is in decline, and we, therefore, reviewed publications in the Journal of Antimicrobial Chemotherapy (JAC) and Antimicrobial Agents and Chemotherapy (AAC) in 4 of the last 14 years . In absolute numbers the total number of UK first author publications in these two journals were 103, 78, 107 and 82 in 1980, 1985, 1990 and 1994 respectively . The percentage of first author papers from the UK in JAC was 35%, 21%, 24%, 23% and in AAC was 5.7%, 4.9%, 5.1% and 4.7% for the years 1980, 1985, 1990 and 1994 respectively . Within the UK there has been a relative decline in the number of publications produced by NHS hospital departments and an increase in those produced by universities . Ten institutions (four universities, two pharmaceutical companies and four NHS departments) produced almost half of the UK publications . There is no room for complacency about the state of British antimicrobial research and the relative decline in the NHS hospital sector's contribution, the largest contributor numerically, even before the full impact of the ongoing NHS reforms, is cause for concern.

J Antimicrob Chemother, 1996 Dec, 38(6), 1001 - 12
Optimising antimicrobial drug use in surgery: an intervention study in a Dutch university hospital; Gyssens IC et al.; Following a one-month prospective study of antimicrobial drug use in surgical departments, new guidelines were implemented . The review was repeated after two years . In both study periods, one third of patients were prescribed antimicrobial drugs . Prophylactic antibiotic consumption decreased from 0.75 to 0.53 defined daily doses/operation . Compliance with guidelines improved from 32% to 79% . Duration of prophylaxis > 24 h decreased from 21% to 8% . Single dose prophylaxis increased from 34% to 80% . Quality of the prophylactic courses improved, as evaluated by experts using established criteria . For prophylaxis, cost savings amounted to 57% . Better quality of therapeutic courses was associated with a cost increase of 15% . Indicators of satisfactory outcome with the new policy were a stable median length of stay (5.5 days in the first review and 5.0 days after intervention) and a reduction in the number of nosocomial infections treated with antimicrobial drugs/100 bed days (1.0 before intervention vs 0.77 after intervention).

J Antimicrob Chemother, 1996 Dec, 38(6), 963 - 8
The Etest for antimicrobial susceptibility testing of Bartonella henselae; Wolfson C et al.; The in-vitro susceptibility of 10 isolates of Bartonella henselae was assessed using the Etest . The organisms, one reference human strain and nine feline isolates, were grown on chocolate agar and the Etests read at days 5, 8 and 11 . Six antibiotics, erythromycin, azithromycin, doxycycline, ciprofloxacin, rifampicin and vancomycin were evaluated . The results correlated well with published results using agar dilution . The results confirmed the high in-vitro susceptibility of B . henselae to erythromycin, azithromycin, doxycycline and rifampicin and to a lesser extent ciprofloxacin . The majority of isolates were resistant to vancomycin . Although in-vitro results of B . henselae susceptibility testing may not necessarily correlate with clinical response, the Etest may be a simpler way for laboratories to monitor for the development of resistance particularly in the setting of relapsing infection.

Nihon Kyobu Shikkan Gakkai Zasshi, 1996 Dec, 34(12), 1349 - 53
{Defensin in plasma and in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome}; Ashitani J et al.; We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS) . High levels of plasma defensins were observed in samples from patients with ARDS . Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis . In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects . A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS . These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

J Cardiovasc Surg (Torino), 1996 Dec, 37(6), 631 - 3
Prosthetic valve endocarditis due to Legionella pneumophila; Chen TT et al.; Prosthetic valve endocarditis is a potential complication of valve replacement surgery and warrants prompt diagnosis and appropriate treatment . Thus, the blood culture in addition to providing an etiological organism is important in establishing appropriate antibiotic therapy . A case of prosthetic valve endocarditis (PVE) is presented with repeatedly negative blood cultures at a community hospital and refractory to prolonged therapy with standard antibiotic regimens . Appropriate workup eventually identified the causative organism as Legionella pneumophila, and antimicrobial therapy directed against Legionella combined with a repeat valve replacement effectively treated this case . Aspects of culture-negative PVE including the microbiology and etiology are discussed . Legionella endocarditis represents an important cause of culture negative PVE and should be considered in the differential diagnosis of culture negative PVE refractory to standard antimicrobial therapy.

Br J Urol, 1996 Dec, 78(6), 940 - 1
Burns to the genitals and the perineum in children; Michielsen D et al.; OBJECTIVE: To determine the management of perineal and genital burns in children . PATIENTS AND METHODS: Twenty-seven children (aged 6 months to 12 years) suffering from genital or perineal burns between 1981 and 1995 were reviewed . Most burns occurred in boys (70%), were due to scalds (85%) and caused superficial second-degree lesions (63%) . The initial treatment consisted of topical antimicrobials or grafting with allografts . RESULTS: Spontaneous healing by conservative therapy, not early excision therapy, occurred in 96% of the patients . Contractures occurred in two patients and were treated with multiple Z-plasties and circumcision . CONCLUSION: The management of perineal and genital burns in children should be conservative.

Arch Dis Child, 1996 Dec, 75(6), 482 - 8
Dexamethasone and bacterial meningitis in Pakistan; Qazi SA et al.; The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes . A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis . Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge . Forty eight patients received dexamethasone and 41 placebo . Initial antimicrobial drugs used were ampicillin and chloramphenicol . For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness . Seventeen of 89 (19%) patients died . The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo . Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death . Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively . Altered state of consciousness was a predictor of neurological sequelae . The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss . No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis . Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.

Hinyokika Kiyo, 1996 Dec, 42(12), 981 - 2
{A case of Fournier's gangrene with healing accelerated by argatroban}; Soda T et al.; A 58-year-old man was admitted to our hospital complaining of pain and marked swelling of scrotum and perineum . Physical and radiological examinations revealed gas-producing gangrenous changes involving the scrotum . Debridement was urgently carried out . Following the debridement under control of diabetes mellitus, antimicrobial agents and argatroban, a newly synthesized antithrombin medicine, were administered . Argatroban was used for the purpose of improving vascular insufficiency . Healthy granulation tissue was present five weeks later . Then surgical closure was carried out . Computed tomography was useful to make early diagnosis, and argatroban was thought to accelerate healing of the gangrene.

Protein Eng, 1996 Dec, 9(12), 1219 - 24
Specific antimicrobial and hemolytic activities of 18-residue peptides derived from the amino terminal region of the toxin pardaxin; Thennarasu S et al.; Peptides are part of the host defense system against bacteria and fungi in species right across the evolutionary scale . However, endogenous antibacterial peptides are often composed of 25 residues or more and, therefore, are not ideal for therapeutic use . Hence it is of considerable interest to design and engineer short peptides having antimicrobial activity . Peptides composed of 18 amino acids, derived from the N-terminal region of the 33-residue toxin pardaxin (PX), GFFALIPKIISSPLFKTLLSAVGSALSSSGEQE, were synthesized and examined for biological activities . Peptide corresponding to the 1-18 stretch of PX exhibited antimicrobial activity only against Escherichia coli and not against Gram-positive microorganisms . The peptide also did not possess hemolytic activity . Replacement of P7 by A resulted in a peptide possessing both antibacterial and hemolytic activity . Substitution of both K residues by Q in the 'A' analog resulted in a peptide having only hemolytic activity . Conformational analysis of these peptides and investigation of their model membrane permeabilizing activities indicated that selective activity can be explained by their biophysical properties . Hence, by a rational design approach based on biophysical principles, it should be possible to generate short peptides having specific biological activity.

J Biochem (Tokyo), 1996 Dec, 120(6), 1253 - 60
Tachycitin, a small granular component in horseshoe crab hemocytes, is an antimicrobial protein with chitin-binding activity; Kawabata S et al.; Small granules of horseshoe crab hemocytes contain two known major antimicrobial substances, tachyplesin and big defensin (S5), and at least five protein components (S1 to S6), with unknown functions . In the present study, we examined the biological properties and primary structure of a small granular component S2, named tachycitin . This component was purified from the acid extract of hemocyte debris by two steps of chromatography . The purified tachycitin was a single chain protein with an apparent M(r) = 8,500 on Tricine-SDS-polyacrylamide gel electrophoresis . Ultracentrifugation analysis revealed tachycitin to be present in monomer form in solution . Tachycitin inhibited the growth of both Gram-negative and -positive bacteria, and fungi, with a bacterial agglutinating property . Moreover, tachycitin and big defensin acted synergistically in antimicrobial activities . The amino acid sequence and intrachain disulfide bonds of tachycitin were determined by amino acid and sequence analyses of peptides produced by enzymatic cleavages . The mature tachycitin consisted of 73 amino acid residues containing five disulfide bonds with no N-linked sugar . A cDNA coding for tachycitin was isolated from a hemocyte cDNA library . The open reading frame coded for an NH2-terminal signal sequence followed by the mature peptide and an extension sequence of -Gly-Arg-Lys at the COOH-terminus, which is a putative amidating signal . The COOH-terminal threonine amide released after digestion of tachycitin with lysylendopeptidase was identified . The NH2-terminal 28 residues of tachycitin shows sequence homology to a part of chitin-binding regions found in antifungal chitin-binding peptides, chitin-binding lectins, and chitinases, all of which have been isolated from plants . Tachycitin showed a specific binding to chitin but did not bind with the polysaccharides cellulose, mannan, xylan, and laminarin . Tachycitin may represent a new class of chitin-binding protein family in animals.

J Biochem (Tokyo), 1996 Dec, 120(6), 1130 - 40
Selective interaction of synthetic antimicrobial peptides derived from sapecin B with lipid bilayers; Hirakura Y et al.; By measuring carboxyfluorescein leakage from liposomes and the increase in membrane current through planar lipid bilayer membranes, we examined the capacities of a series of low-molecular-weight cationic amphiphilic peptides derived from the alpha-helix domain of sapecin B for membrane-perturbation and ion-channel formation . Some of these peptides strongly interact with membranes containing acidic phospholipids and phosphatidylethanolamine, with a very negative potential, which are characteristic of the Escherichia coli membrane, in parallel with their antimicrobial activity . In contrast, they do not interact with membranes which predominantly contain choline phospholipids and cholesterol in their outer leaflets, with a slightly negative potential, all of which are characteristic of eukaryotic membranes, thereby providing a molecular basis for their selective toxicity . Membranes doped with these peptides are as permeable to inorganic phosphates as to chloride ions and are far more permeable to cations . The loss of inorganic phosphates may damage bacterial cells due to rapid depletion of cytoplasmic ATP . Examination of the structure-activity relationships of a series of derived peptides in their interaction with a model of the E . coli membrane confirmed the necessity of cationic amphiphilicity for the peptides to attack the bacterial membrane and to exhibit antimicrobial activity.

Appl Microbiol Biotechnol, 1996 Dec, 46(5-6), 587 - 92
The action of antibiotics on the anaerobic digestion process; Sanz JL et al.; Antibiotics can disturb the production of biogas during anaerobic digestion . This study shows a systematic approach to understanding how the different bacterial populations involved in the final conversion of organic matter into methane are inhibited by 15 antimicrobial agents with different specificities and modes of action . The results obtained show the following trends: (i) some inhibitors, such as the macrolide erythromycin, lack any inhibitory effect on biogas production; (ii) some antibiotics, with different specificities, have partial inhibitory effects on anaerobic digestion and decrease methane production by interfering with the activity of propionic-acid- and butyric-acid-degrading bacteria, (e.g . antibiotics that interfere with cell wall synthesis, RNA polymerase activity and protein synthesis, especially the aminoglycosides); (iii) the protein synthesis inhibitors chlortetracycline (IC50 40 mg l-1) and chloramphenicol (IC50 15-20 mg l-1) are very powerful inhibitors of anaerobic digestion . The majority of the antibiotics tested lacked activity against acetoclastic methanogens, being active only on the acetogenic bacteria . However, chloramphenicol and chlortetracycline could cause the complete inhibition of the acetoclastic methanogenic archaea.

Int J Qual Health Care, 1996 Dec, 8(6), 519 - 26
Influence of location and staff knowledge on quality of retail pharmacy prescribing for childhood diarrhea in Kenya; Goel PK et al.; BACKGROUND: Retail pharmacies are important sources of advice on pharmaceuticals in developing countries, where many purchasing decisions are unmediated by medical professionals . For childhood diarrhea, choice of drug sales in pharmacies has been found to be consistently poor, whether with or without prescription, as evidenced by a low use of effective oral rehydration salts (ORS) and high use of marginally effective or ineffective products such as antimotility agents, adsorbents, and antimicrobials . Little information is available about factors influencing prescribing by pharmacy personnel in these settings . This paper reports results of an analysis which examined the influence of rural versus urban location, neighborhood socio-economic status (SES), and clinical knowledge of pharmacy assistants on quality of prescribing in retail pharmacies in Kenya . METHODS: Using WHO treatment guidelines, we measured quality of prescribing in childhood diarrhea as: (1) the proportion of client encounters in which ORS is prescribed (indicating higher quality practice); and (2) the proportion of visits in which an antidiarrheal product is prescribed (lower quality practice) . We obtained data on prescribing in a simple case of childhood diarrhea using surrogate patient visits to 91 pharmacies located in the major urban area of Kenya (Nairobi) and four rural towns . Multivariate logistic regression was used to examine the association between pharmacy predictor variables and the quality of prescribing . RESULTS: No consistent relationship was found between the clinical knowledge of pharmacy assistants and quality of prescribing . Controlling for number of products prescribed, gender of the assessor, and level of knowledge, multivariate analyses indicated that in comparison to rural pharmacies, the odds of prescribing ORS were significantly higher in pharmacies located in high SES (OR = 4.7; 95% CI = 1.4,16.1) or middle SES (OR = 4.5; CI = 1.9,10.6) urban neighborhoods; the odds in low SES urban pharmacies were similar to those in rural areas (OR = 2.0; CI = 0.6,6.2) . The odds of prescribing antidiarrheal products did not differ significantly in any geographic area . CONCLUSIONS: Location of a retail pharmacy in a rural area or in a low-income urban neighborhood was associated with suboptimal quality of prescribing as evidenced by lower use of ORS . No relationship between clinical knowledge and quality of practice was detected . Future research is needed to examine such factors as the influence of intra-pharmacy authority structure, perceived efficacy of pharmaceuticals, local patterns of physician practice, and economic incentives on the quality of prescribing.

Aust Vet J, 1996 Dec, 74(6), 430 - 2
Nocardial peritonitis in a cat; Tilgner SL et al.; OBJECTIVE: To illustrate a successfully managed case of nocardial peritonitis in a cat . DESIGN: Case report . ANIMAL: An 8 year old neutered male Burmese cat presented for nonspecific signs of depression, anorexia, pallor and mild dehydration . Pyrexia, loss of weight and abdominal distension developed despite treatment with amoxycillin-clavulanate and supportive therapy . PROCEDURE: Various medical and surgical procedures were used . RESULTS: Haematology revealed severe inflammatory left shift . Biochemistry showed mild prerenal azotemia . A "ground glass" appearance to the abdomen was seen on radiographs . Fluid collected by abdominocentesis contained "sulphur granules" and had characteristics of a septic exudate . Laparotomy allowed drainage of peritoneal fluid and extensive lavage of the peritoneal cavity . Culture of the fluid revealed Nocardia sp . Sensitivity testing resulted in a change of antimicrobial therapy to trimethoprim-sulphadiazine . CONCLUSION: Response to surgical drainage and change in antibacterial therapy was excellent . No toxic side effects were encountered during the 3 months course of trimethoprim-sulphonamide . The cat made a complete recovery.

Arzneimittelforschung, 1996 Dec, 46(12), 1163 - 8
Chemistry and biological activity of a tryptamine and beta-carboline series of bases; Begum S et al.; Twenty-six derivatives of harmaline and tetrahydroharmine were prepared and characterized by UV, IR, MS, and NMR spectroscopy . They were tested for their antimicrobial, antiplatelet aggregation and cytotoxic activity . Their effect on central nervous system was also studied.

Am J Surg, 1996 Dec, 172(6A), 13S - 19S
Diagnosis and treatment of bacteremia and intravascular catheter infections; Bullard KM et al.; The past decade has witnessed an explosive rise in the rate of bacteremia and intravascular catheter infection . Although gram-negative organisms continue to account for up to one third of these infections, gram-positive organisms have become increasingly prevalent pathogens . Virulent antibiotic-resistant bacterial strains have emerged and present a formidable treatment challenge . Simultaneously, management of catheter infection has evolved . Although patients who develop fungemia, gram-negative bacteremia, or sepsis syndrome are best treated by catheter removal in addition to antimicrobial therapy, an increasing body of evidence suggests that many gram-positive bacterial catheter infections can be treated by use of antimicrobial agents without catheter removal . Advances in catheter design and immunotherapy for sepsis syndrome also hold promise . Despite these innovations, determining the initial need for catheter placement, adherence to meticulous sterile surgical technique during insertion, and subsequent fastidious catheter maintenance remain the mainstays of preventing these potentially disastrous infections.

J Clin Periodontol, 1996 Dec, 23(12), 1133 - 6
Gingival fluid tetracycline release from bioerodible gels; Maze GI et al.; Intracrevicular antimicrobial therapy is consistent with the site-specific nature of periodontitis . Considerable research has focused on the use of nonresorbable fibers . However, a bioerodible system is desirable . The purpose of this study was to assess tetracycline release and safety following a single application of a syringable 35% tetracycline hydrochloride in a lactic-glycolic acid gel . 31 generally healthy adult volunteers (mean age = 59 years) were enrolled in and completed this randomized, double-blind eight day study . 2, 6-10 mm non-adjacent interproximal pockets that bled on pocket probing were chosen as experimental sites in each subject . I experimental site and the surrounding gingival crevice received small particle size tetracycline in gel while the other site received larger particle size tetracycline in gel . Gingival crevicular fluid (GCF) was collected prior to treatment and 15 min, 1, 2, 3, 4 and 8 days post-treatment . GCF tetracyline concentrations were determined by agar diffusion bioassay and GCF volume measurements . 61% and 71% of sites had > or = 100 micrograms/ml tetracycline 3 days following application of large (mean concentration = 430 +/- 92 micrograms/ml) and small particle gels (mean concentration = 418 +/- 70 micrograms/ml), respectively . 37% and 55% of sites had measurable tetracycline 8 days after placement of large (mean concentration = 86 +/- 31 micrograms/ml) and small particle gels (mean concentration = 293 +/- 79 micrograms/ml), respectively . The most common adverse event was "bitter taste" (10% of subjects) . Based upon the reduction in probing depths and % of sites bleeding on probing at 8 days relative to pretreatment, and the absence of any serious adverse events, it is concluded that these bioerodible gels are safe, and since the bacteriostatic range for most putative periodontopathogens is in the 2-10 micrograms/ml range, the tetracycline levels observed at days 3 and 8 likely represent significant antimicrobial efficacy.

J Clin Periodontol, 1996 Dec, 23(12), 1084 - 92
In vitro and in vivo studies on salifluor/PVM/MA copolymer/NaF combination as an antiplaque agent; Nabi N et al.; Salifluor (5-n-octanoyl-3'-trifluoromethyl-salicylanilide), a broad spectrum antimicrobial agent, was investigated for its ability to inhibit dental plaque formation . A combination of salifluor with PVM/MA copolymer and NaF was optimized for its antiplaque effect in mouthrinse and dentifrice formulations based on a series of both laboratory and clinical studies . It was found that salifluor, a highly hydrophobic compound, could not be adequately solubilized with the conventional amount of sodium lauryl sulfate (SLS), the most commonly used anionic surfactant in oral hygiene products . However, it was possible to prepare stable mouthrinse formulations using a mixed surfactant system containing both anionic and nonionic surfactants . The most suitable mixture was found to be a combination of SLS, Pluronic and Tauranol in a proportion of 1:1:1 . This combination provided adequate stability and high antimicrobial activity as determined by in vitro microbiological tests . Addition of a PVM/MA copolymer to the formulation improved the adsorption and retention of salifluor on stimulated tooth surfaces in vitro (saliva coated hydroxyapatite disks) by almost two-fold and also increased the antiplaque efficacy in both laboratory and human clinical studies . It was also found that a non fluoride dentifrice containing a combination of salifluor and PVM/MA copolymer with a dicalcium phosphate dihydrate abrasive, was highly effective in reducing smooth surface and fissure caries in rats . The results of the present studies demonstrated that salifluor is an effective antiplaque agent in mouthrinse and dentifrice when carefully formulated to maximize its delivery and bioavailability on oral surfaces . They also illustrated the difficulties encountered in exploiting the antimicrobial efficacy of highly hydrophobic, nonionic antimicrobial agents such as salifluor in commonly used oral hygiene vehicles.

J Clin Periodontol, 1996 Dec, 23(12), 1068 - 72
Saliva composition in children and young adults with Papillon-Lefèvre syndrome; Lundgren T et al.; The aim of the present study was to evaluate the salivary secretion rate and composition in a group of 16 children and young adults (6-27 years) with Papillon-Lefevre Syndrome (PLS), and to compare the findings with a group (n = 16) of healthy controls . Unstimulated and stimulated whole saliva was collected at least 2 h after meals and the secretion rate determined . The stimulated saliva was assessed for buffer capacity, total protein, peroxidase and hexosamine, while the unstimulated samples were evaluated for total protein, lysozyme, thiocyanate, lactoferrin and salivary IgA . Both the unstimulated (p < 0.01) and stimulated (p < 0.05) saliva secretion rates were significantly lower among the PLS patients compared with the controls . Furthermore salivary buffer capacity was significantly (p < 0.01) lower in the PLS patients . The total protein content in saliva was comparatively high in the study group, while the concentrations of immunoglobulins and non-immunoglobulins were within normal ranges . When calculating the output of the assessed antimicrobial factors, the mean peroxidase level in stimulated whole saliva was found to be significantly (p < 0.01) lower in the PLS patients than in the healthy controls . In conclusion, the present study indicates an impaired water secretion and a somewhat altered saliva gland function in children and young adults with PLS.

Biol Chem, 1996 Dec, 377(12), 765 - 74
Retroviral proteases: structure, function and inhibition from a non-anticipated viral enzyme to the target of a most promising HIV therapy; von der Helm K; Retrovirally encoded proteases are responsible for the maturation of immature viral particles yielding mature, infectious virus . This is done by apparent (auto)-processing and self-activation of the protease (PR) from a larger viral gag-PR-(pol) protein (zymogen) precursor and subsequent processing of the viral reverse transcriptase (RT) and integrase (IN), and the gag protein precursor into mature gag proteins . Only the matured components are capable of forming capsids for intact, infectious viruses . Blocking this proteolytic process results in production of immature, non-infective virions . All retroviral proteases are aspartic-type proteases . Determination of the three-dimensional structure revealed retroviral proteases as small, nearly symmetric homodimers . This prompted de novo design of inhibitors for the HIV protease taking advantage of the unique symmetric structure of the active center, unparalleled by cellular proteases . The novel substances inhibit in vitro the HIV protease at nanomolar/subnanomolar concentrations and exhibit very low toxicity . They are inactive against human proteases such as renin or pepsin . The HIV protease inhibitors (PI) represent a promising alternative to the reverse transcriptase (RT) inhibitors (AZT, ddC, ddI) hitherto used with limited success for HIV chemotherapy . Clinical studies confirmed the low toxicity but revealed a pharmacological pattern typical for these hydrophobic compounds, such as low water solubility, poor oral bioavailibility, and short plasma half-life . Typical for antimicrobial agents, also a resistance phenomenon became evident . Latest clinical results show, however, promisingly that both problems might be overcome by application of the PI in combination with RT inhibitors (such as AZT, ddI or ddC) exerting a remarkable synergistic antiviral effect with lasting restoration of the CD4-T-cell level.

Acta Odontol Scand, 1996 Dec, 54(6), 391 - 7
Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia; Kirstila V et al.; This study evaluates the effects of two oral hygiene products containing nonimmunoglobulin antimicrobial agents on whole saliva and on subjective oral symptoms in patients with xerostomia . Twenty patients used a lactoperoxidase-system-containing toothpaste (Biotene) combined with the use of a mouthrinse (Biotene), comprising also lysozyme and lactoferrin, for 4 weeks . Saliva samples were collected at base line, after 4 weeks' use of the products, and at the end of a 4-week washout period . Samples were analyzed for selected biochemical and microbiologic factors . The effects on subjective oral symptoms were also recorded . A 4-week daily use of toothpaste and mouthrinse relieved the symptoms of oral dryness in 16 patients . The levels of salivary hypothiocyanite, lysozyme, lactoferrin, or myeloperoxidase activity did not change, but there was a significant decrease in salivary pH (P < 0.05), total peroxidase activity (P < 0.05), and total protein content (P = 0.01) . In patients with the lowest salivary flow rates (n = 5) a significant (P > or = 0.04) increase was detected in salivary hypothiocyanite concentrations . No major changes occurred in salivary microflora . The products relieved subjective oral symptoms in most xerostomic patients, but this was not necessarily related to the presence of antimicrobial agents.

Int J Clin Pharmacol Ther, 1996 Dec, 34(12), 555 - 7
Treatment of acute biliary tract infections with ofloxacin: a randomized, controlled clinical trial; Karachalios GN et al.; The combination of penicillin with an aminoglycoside has been recommended as an initial treatment of choice for patients with acute infections of the biliary tract . However, many patients have incidence of renal problems and for this reason aminoglycosides must be avoided . Newer antimicrobial agents with lesser nephrotoxic effects will be tried . We, therefore, performed a prospective, randomized trial of ofloxacin, a new quinolone and ceftriaxone in patients with acute biliary tract infections . Fifty-two patients with severe biliary tract infections (cholecystitis and cholangitis) were randomly assigned to receive either ofloxacin (n = 28) or ceftriaxone (n = 24) . The 2 groups receiving antibiotics were similar with respect to all clinical and laboratory parameters . Bacteria were documented in 48% of patients in the ofloxacin group and in 46% in the ceftriaxone group . The percentage of patients with a clinical cure or significant improvement was the same in the 2 groups . No significant difference was noted between the 2 treatment groups with respect to drug toxicity . These data suggest that intravenous ofloxacin followed by oral administration is an effective and safe single drug for the therapy of patients with acute biliary tract infections.

Clin Transplant, 1996 Dec, 10(6 Pt 2), 668 - 75
Liver transplantation for hepatitis B cirrhosis: clinical sequela of passive immunization; al-Hemsi B et al.; Aggressive administration of hepatitis B immune globulin (HBIg) has been shown to prevent hepatitis B viral (HBV) infection of the allograft; however, the clinical sequela of such therapy has not been previously described . We reviewed our experience with high dose, intravenous infusion of an intramuscular HBIg preparation to assess the effectiveness and complications of such therapy . Thirty three orthotopic liver transplants (OLTx) were performed in 32 patients with chronic HBV cirrhosis at the University of Virginia between March 1990 and June 1995 . Twenty-nine of 32 (91%) patients remain free of HBV recurrence (defined by undetectable serum HBsAg and HBV-DNA) after a mean of 21 months (2-54 months), with one patient requiring retransplantation . Three (10%) patients died of non-HBV causes (two vascular events, one infectious event) . Twenty episodes of acute cellular rejection were treated in 18 patients (two had two episodes) . Sixteen rejections occurred within 18 d of transplant, 19 by day 120, and one late rejection occurred at 18 months owing to medication non-compliance . Eighteen patients had at least one documented infection . Six patients were treated for CMV infection (five empirically) . Eight patients were treated for HSV infections (seven mild herpetic labialis and one herpetic keratitis) . Four patients had documented fungal infection (one mucormycosis pneumonia and three minor superficial mucosal infections) . With the exception of one necrotizing pneumonia, 11 bacterial infections were successfully treated with conventional antimicrobial agents . No patient developed post-transplant lymphoproliferative disorder . Symptoms associated with HBIg infusion were intermittent but frequent and consisted of myalgias, predominantly back pain (90%), headache (20%) and flushing (5%) . No patient experienced anaphylaxis, fever, rash, arthritis or hypotension . Despite the potential for mercury toxicity and HCV transmission in the HBIg formulations currently available in the United States, serum mercury levels remained below standards for industrial exposure (60 micrograms/ml), and only one individual developed post-transplant HCV infection after receiving multiple units of unscreened blood prior to 1991 . Summary: High-dose HBIg prevented HBV infection of the allograft in 29 of 32 patients transplanted for HBV cirrhosis with three non-HBV associated deaths . The intravenous infusion of HBIg was frequently associated with minor side effects that were safely tolerated by patients . The risk of HCV transmission and mercury toxicity are minimal, but support the need for a new intravenous formulation of HBIg . HBIg therapy successfully decreased post-OLTx HBV recurrence with no clinical events associated with immunosuppression . Patients did non experience allergic or infusion-related complications that altered or terminated therapy . Manufacturing modifications of HBIg may allow for improved patient tolerance and decreased risks.

J Vet Med Sci, 1996 Dec, 58(12), 1227 - 9
Monoclonal antibody against bovine Lactoferricin and its epitopic site; Shimazaki K et al.; Bovine lactoferricin (LFcin B) is a strong antimicrobial peptide derived from N-lobe of lactoferrin . To study the immunochemical and structural properties of LFcin B, monoclonal antibody (mAb) was prepared and the amino acid sequence concerning with the binding to mAb has been identified . Mice injected with LFcin B showed no production of antibody specific to this peptide, whereas those with LFcin B-KLH conjugate produced anti-LFcin B antibodies . None of the mAb reacted with bovine lactoferrin C-lobe, human lactoferrin or LFcin H . By the reactivity of the mAb against the peptides synthesized on cellulose membranes using SPOTs and against chemically modified derivatives of LFcin B, the antigenic determinant of LFcin B was identified to be the sequence of "QWR".

Biol Pharm Bull, 1996 Dec, 19(12), 1602 - 6
Synthesis and biological activity of four kinds of reversed peptides; Lie BL et al.; We have synthesized four kinds of reversed peptides of various physiologically active peptides, which inhibit TNF (tumor necrosis factor) cytotoxicity, produce NGF (nerve growth factor), exert antimicrobial activity and inhibit cell attachment, respectively . They were examined for their biological activity in comparison with that of normal peptides, that is, naturally occurring peptides . The reversed peptides induce similar activities, but to a lesser extent than those of the normal peptides, respectively . These results indicate that there may be conformationally ambiguous binding in some of the naturally occurring ligand-protein interactions . This method may be useful as a tool to rapidly generate a novel lead peptide with the desired biological function from a naturally occurring active peptide.

Nord Med, 1996 Dec, 111(10), 348 - 51
{Tetracyclines as anti-inflammatory treatment in skin diseases}; Autio P et al.; Tetracyclines are broad-spectrum bacteriostatic antimicrobials drugs, traditionally used in dermatology for the treatment of acne . Owing to their beneficial antiinflammatory properties, and the low risk and modest side effects associated with them, tetracyclines are also useful in treating several other skin diseases-either alone, or in combination regimens to reduce the intensity of the immunosuppressive effect.

Microbiol Rev, 1996 Dec, 60(4), 641 - 96
Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses; Davey HM et al.; The most fundamental questions such as whether a cell is alive, in the sense of being able to divide or to form a colony, may sometimes be very hard to answer, since even axenic microbial cultures are extremely heterogeneous . Analyses that seek to correlate such things as viability, which is a property of an individual cell, with macroscopic measurements of culture variables such as ATP content, respiratory activity, and so on, must inevitably fail . It is therefore necessary to make physiological measurements on individual cells . Flow cytometry is such a technique, which allows one to analyze cells rapidly and individually and permits the quantitative analysis of microbial heterogeneity . It therefore offers many advantages over conventional measurements for both routine and more exploratory analyses of microbial properties . While the technique has been widely applied to the study of mammalian cells, is use in microbiology has until recently been much more limited, largely because of the smaller size of microbes and the consequently smaller optical signals obtainable from them . Since these technical barriers no longer hold, flow cytometry with appropriate stains has been used for the rapid discrimination and identification of microbial cells, for the rapid assessment of viability and of the heterogeneous distributions of a wealth of other more detailed physiological properties, for the analysis of antimicrobial drug-cell interactions, and for the isolation of high-yielding strains of biotechnological interest . Flow cytometric analyses provide an abundance of multivariate data, and special methods have been devised to exploit these . Ongoing advances mean that modern flow cytometers may now be used by nonspecialists to effect a renaissance in our understanding of microbial heterogeneity.

Intensive Care Med, 1996 Dec, 22(12), 1307 - 14
Severe community-acquired pneumonia in ICUs: prospective validation of a prognostic score; Leroy O et al.; OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively . DESIGN: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994 . SETTING: Four medical ICUs in the north of France . PATIENTS: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index . Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index . RESULTS: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5) . An index was obtained by adding each patient's points . According to a receiver operating characteristic curve, the cut-off value of this index was 2.5 . In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98 . CONCLUSION: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Pharmazie, 1996 Dec, 51(12), 927 - 31
Synthesis of novel thiazolo{4,5-d}pyrimidine derivatives for antimicrobial, anti-HIV and anticancer investigation; Rida SM et al.; Some novel thiazolo{4,5-d}pyrimidines containing 6-arylideneamino (3a-e) . 2-dicyanomethylidene (5a), 2-(cyanoethoxy carbonyl) methylidene (5b) or 2-hydrazono (7a, b) moieties were synthesized . The prepared compounds were tested in vitro for their antibacterial, antifungal, anti-HIV and anticancer activities . Most of them showed promising antifungal activity, but only a few compounds exhibited anticancer activity.

Eur J Gastroenterol Hepatol, 1996 Dec, 8(12), 1161 - 3
Helicobacter pylori reinfection is rare in peptic ulcer patients cured by antimicrobial therapy; Miehlke S et al.; BACKGROUND: Cure of H . pylori infection in peptic ulcer patients significantly reduces the risk of ulcer recurrence . Since data on the rate of H . pylori reinfection in patients undergoing successful anti-H . pylori therapy are sparse, this study was conducted with the aim of determining the H . pylori reinfection rate in peptic ulcer patients receiving antibacterial treatment to heal their ulcer and cure H . pylori infection . METHODS: A total of 217 patients with H . pylori-associated duodenal or gastric ulcer were followed up after treatment with various antibacterial regimens resulting in histologically documented cure of H . pylori infection . Endoscopic and histological examinations were performed 4 weeks after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic symptoms occurred . To assess the H . pylori status two antral and two corpus biopsies were obtained for histological examination . RESULTS: Out of 217 patients with initially cured H . pylori infection 175 were available for endoscopic follow-up . At the time of analysis, 44 patients were re-examined after 1 year, 113 patients after 2 years and 18 patients after 5 years, giving a total of 360 patient years of follow-up . The mean duration of follow-up was 24.7 months . H . pylori reinfection was confirmed histologically in eight patients, three of whom becoming H . pylori-positive again within the first year of follow-up . Six of the eight patients with H . pylori reinfection also suffered an ulcer relapse . Eight cases of reinfection in 360 patient years represents an overall reinfection rate of 2.2% . Within the first 2 years of follow-up the reinfection rate was 0.8% per year . CONCLUSION: Our data suggest that H . pylori reinfection is rare in peptic ulcer patients receiving successful anti-H . pylori therapy . H . pylori reinfection frequently coincides with ulcer recurrence . Cure of H . pylori infection results in cure of peptic ulcer disease, provided H . pylori reinfection does not occur.

Inflammation, 1996 Dec, 20(6), 693 - 705
Membrane-stabilizing, anti-inflammatory interactions of macrolides with human neutrophils; Anderson R et al.; The effects of the macrolide antimicrobial agents azithromycin, clarithromycin, erythromycin and roxithromycin on the prooxidative activity of stimulated human neutrophils have been investigated in vitro . Superoxide generation by activated neutrophils was measured by lucigenin-enhanced chemiluminescence . At the concentrations used (2.5-80 micrograms/ml) none of the test agents was cytotoxic, nor did they possess superoxide-scavenging properties . Treatment of neutrophils with all 4 macrolides was accompanied by dose-related inhibition of superoxide production by cells activated with FMLP or the calcium ionophore (A23187), while the responses activated by phorbol myristate acetate (PMA) or opsonized zymosan were minimally affected . The anti-oxidative interactions of roxithromycin with FMLP-activated neutrophils were neutralized by pretreatment of the cells with low, non-cytotoxic concentrations (0.5 microgram/ml) of the prooxidative, proinflammatory bioactive phospholipids, lysophosphatidylcholine (LPC), platelet-activating factor (PAF) and lyso-PAF (LPAF) . Using an assay of membrane-stabilizing activity, the macrolides antagonized the membrane-disruptive effects of LPC, PAF and LPAF, without affecting enzymes involved in their synthesis . These membrane-stabilizing interactions of macrolides with neutrophils may counteract the proinflammatory, prooxidative activity of several bioactive lipids which have been implicated in the pathogenesis of bronchial asthma.

Semin Respir Infect, 1996 Dec, 11(4), 272 - 84
Nontuberculous mycobacterial pulmonary disease in cystic fibrosis; Olivier KN et al.; Since 1990, there have been an increasing number of reports of nontuberculous mycobacteria (NTM) recovered from lower respiratory tract specimens of patients with cystic fibrosis (CF) lung disease . The eight reports from series of prospectively screened patients collectively note a prevalence of approximately 13% . Reasons for the increased reports in CF patients may be related to: (1) active searching for NTM; (2) complications of advancing survival length in which more pathogens are emerging; (3) improvements in culture technique that decrease bacterial overgrowth: (4) factors that favor transmission such as contaminated hospital water supplies; and (5) a more susceptible host reflecting increasing NTM infection in the general population . Distinguishing airway colonization by NTM from pathogenic NTM infection that contributes to the progression of the underlying CF lung disease can be particularly difficult . Treatment of NTM in CF can also be more difficult because: (1) altered drug absorption and metabolism, (2) pre-treatment polypharmacy including multiple antimicrobials, and (3) the susceptibility of other pathogens to some antimycobacterial agents confounding assessment of NTM treatment response.

J Interferon Cytokine Res, 1996 Dec, 16(12), 1015 - 9
Delivery of human interferon-gamma via gene transfer in vitro: prolonged expression and induction of macrophage antimicrobial activity; Stoeckle MY et al.; Daily parenteral administration of exogenous interferon-gamma (IFN-gamma) induces or accelerates recovery in experimental and human infections . To develop an alternative delivery system, a replication-defective recombinant adenovirus expressing human IFN-gamma was constructed . The complete coding region of IFN-gamma was amplified by RT-PCR and inserted into an adenovirus cloning vector under the control of a human cytomegalovirus promoter . Recombinant adenovirus containing the IFN-gamma minigene (dAv-IFN-gamma) was isolated from 293 cells co-transfected with the linearized plasmid and an E1 region-deleted fragment of adenovirus genome . Following in vitro infection with dAv-IFN-gamma, dose-dependent and time-dependent expression of IFN-gamma, mRNA and production of soluble protein were demonstrated in human diploid fibroblat and HeLa cell cultures by Northern blot and ELISA, respectively . Extracellular protein secretion persisted for > = 4 weeks following initial transfection, and secreted IFN-gamma induced both antiviral activity (8000-25,000 U/ml) and macrophage activation with killing of intracellular Toxoplasma gondii and leishmania donovani . These results establish that dAv-IFN-gamma generates long-term secretion of biologically active IFN-gamma in vitro and suggest that this vector may be a useful delivery system for cytokine therapy.

Pediatr Clin North Am, 1996 Dec, 43(6), 1165 - 81
An evidence-based approach to treating otitis media; Rosenfeld RM; More than 20 years ago, a shrewd clinician remarked, "There is little evidence that those antimicrobial agents which hypothetically or in vitro are more effective .. . are superior in the treatment of otitis when compared to penicillin alone." Several hundred clinical trials later, the advantages of broad spectrum drugs remain unproved, and questions remains as to whether antibiotics are required for most episodes of AOM . Further, antibiotics have been demoted to the status of optional therapy for OME . This situation is unlikely to change as new studies with new antibiotics proliferate . What is clear, however, is that accelerated patterns of bacterial resistance mandate an evidence-based approach to managing otitis media . Bacteria have an uncanny ability to learn new mechanisms of antibiotic resistance . A large part of bacterial "education" has undoubtedly been fueled by antibiotic prescriptions from well-intentioned physicians, with unrealistic expectations of drug efficacy . A judicious approach to antibiotic treatment of otitis media can result only from knowing the spontaneous course of the disorder and incremental effect of antibiotics on clinical outcomes . In this article, a series of unifying concepts are developed to help practicing clinicians with an evidence-based approach to managing otitis media . Critical review of the published evidence suggests that the most favorable outcomes from medical treatment will occur if practitioners: appreciate the favorable natural history of untreated otitis media realize that OME may take months to resolve following a single AOM episode modify risk factors to improve the odds of spontaneous resolution use pneumatic otoscopy and confirmatory tympanometry to diagnose OME recognize the limited impact of antibiotic therapy on treatment and prevention balance the benefits of antibiotics against the risk of accelerated bacterial resistance avoid repetitive, prolonged, or prophylactic antibiotic treatment of chronic OME avoid ineffective therapy, such as antihistamine/decongestant preparations An important aspect of management is helping caregivers understand the natural history of otitis media and the impact of medical treatment on shortterm and long-term outcomes . Realistic expectations on the part of all involved parties should facilitate rational decisions about watchful waiting, medical therapy, and the need for surgical intervention.

Plant Physiol, 1996 Dec, 112(4), 1669 - 77
Molecular characterization of berberine bridge enzyme genes from opium poppy; Facchini PJ et al.; In Papaver somniferum (opium poppy) and related species, (S)-reticuline serves as a branch-point intermediate in the biosynthesis of numerous isoquinoline alkaloids . The berberine bridge enzyme (BBE) ({S}-reticuline:oxygen oxidoreductase {methylene bridge forming}, EC 1.5.3.9) catalyzes the stereospecific conversion of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon of (S)-scoulerine and represents the first committed step in the pathway leading to the antimicrobial alkaloid sanguinarine . Three unique genomic clones (bbe1, bbe2, and bbe3) similar to a BBE cDNA from Eschscholtzia californica (California poppy) were isolated from opium poppy . Two clones (bbe2 and bbe3) contained frame-shift mutations of which bbe2 was identified as a putative, nonexpressed pseudogene by RNA blot hybridization using a gene-specific probe and by the lack of transient expression of a chimeric gene fusion between the bbe2 5' flanking region and a beta-glucuronidase reporter gene . Similarly, bbe1 was shown to be expressed in opium poppy plants and cultured cells . Genomic DNA blot-hybridization data were consistent with a limited number of bbe homologs . RNA blot hybridization showed that bbe genes are expressed in roots and stems of mature plants and in seedlings within 3 d after germination . Rapid and transient BBE mRNA accumulation also occurred after treatment with a fungal elicitor or with methyl jasmonate . However, sanguinarine was found only in roots, seedlings, and fungal elicitor-treated cell cultures.

J Vet Pharmacol Ther, 1996 Dec, 19(6), 460 - 5
Evaluation of the dorsal aorta cannulation technique for pharmacokinetic studies in Atlantic salmon (Salmo salar) in sea water; Sohlberg S et al.; The antimicrobial drug flumequine was given intravascularly and orally to cannulated and non-cannulated Atlantic salmon (Salmo salar) in sea water at 11 degrees C . The cannulated fish were divided into two groups, which were given flumequine (25 mg/kg) intravenously into the caudal vein (n = 8) and orally via a stomach tube down the oesophagus (n = 8) . After a washout period of 2 days, the intravenously administered fish were given the drug orally, and the orally administered fish were given the drug intravenously . Blood samples were taken at different time points after drug administration through a cannula inserted into the dorsal aorta . The fish in the non-cannulated group were either given flumequine intravenously or orally, and blood samples were collected by killing five fish at predetermined time points after administration . The haematocrit values were measured in all the fish daily for 4 days after drug administration and thereafter, in all the collected blood samples throughout the whole experiment . The haematocrit values differed significantly between the cannulated and the non-cannulated fish . We found low haematocrit values and slow drug elimination in the cannulated groups, compared with higher haematocrit values and faster drug elimination in the non-cannulated groups, but further investigations are needed to prove any causal relations of this observation . The volume of distribution (Vd(ss)) was twice as large in the cannulated groups compared with the non-cannulated group, in the fish administered the drug intravenously . In the last part of the elimination phase, the half-lives differed considerably between the cannulated and the non-cannulated groups both after oral and intravenous administration . The slower depletion of the drug concentration in the plasma of the cannulated fish is due to the large Vd(ss) as there are only small differences in clearance (ClT) between the groups . In this study the elimination of flumequine in cannulated Atlantic salmon differed from the elimination of flumequine in non-cannulated Atlantic salmon.

J Vet Pharmacol Ther, 1996 Dec, 19(6), 431 - 8
The disposition of five therapeutically important antimicrobial agents in llamas; Christensen JM et al.; The disposition of five therapeutic antimicrobial agents was studied in llamas (Lama glama) following intravenous bolus administration . Six llamas were each given ampicillin, tobramycin, trimethoprim, sulfamethoxazole, enrofloxacin and ceftiofur at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg, 15 mg/kg, 5 mg/kg, and 2.2 mg/kg of body weight, respectively, with a wash out period of at least 3 days between treatments . Plasma concentrations of these antimicrobial agents over 12 h following i.v . bolus dosing were determined by reverse phase HPLC . Disposition of the five antimicrobial agents was described by a two compartment open model with elimination from the central compartment, and also by non-compartmental methods . From compartmental analysis, the elimination rate constant, half-life, and apparent volume of distribution in the central compartment were determined . Statistical moment theory was used to determine noncompartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at steady state . Based on the disposition parameters determined, and stated assumptions of likely effective minimum inhibitory concentrations (MIC) a dose and dosing interval for each of five antimicrobial agents were suggested as 6 mg/kg every 12 h for ampicillin; 4 mg/kg once a day or 0.75 mg/kg every 8 h for tobramycin; 3.0 mg/kg/15 mg/kg every 12 h for trimethoprim/sulfamethoxazole; 5 mg/kg every 12 h for enrofloxacin; and 2.2 mg/kg every 12 h for ceftiofur sodium for llamas . Steady-state peak and trough plasma concentrations were also predicted for the drugs in this study for llamas.

Aliment Pharmacol Ther, 1996 Dec, 10(6), 1001 - 4
High-dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection; Malaty H et al.; BACKGROUND: The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H . pylori infections . METHODS: Normal volunteers with H . pylori infection received high-dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s . for 14 days . The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously . Those receiving lansoprazole plus amoxycillin had not been previously treated . Four to 6 weeks after ending antimicrobial therapy, H . pylori status was determined by Genta stain of gastric mucosal biopsies . RESULTS: Forty-three volunteers entered the study and 41 completed it . The overall success with high-dose proton pump inhibitor plus amoxycillin was 34.9% . For the individual regimens the per-protocol results were 48% (95% CI = 28-69%) with lansoprazole and 12.5% (95% CI = 2-38%) with omeprazole . Compliance was > 95% for both regimens . Side-effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw . Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non-smokers . The level of the pre-treatment urea breath test also did not predict outcome . CONCLUSION: High-dose proton pump inhibitor plus amoxycillin combinations for treatment of H . pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate . These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.

Clin Pediatr (Phila), 1996 Dec, 35(12), 629 - 33
Comparative evaluation of cefixime versus amoxicillin-clavulanate following ceftriaxone therapy of pneumonia; Amir J et al.; Preliminary results have recently shown that an early switch from parenteral antimicrobials to an oral substitute provides an effective means of treating pneumonia in pediatric patients . In a controlled randomized study, 62 children with community-acquired lobar/segmental pneumonia were selected to receive 8 days of cefixime or amoxicillin-clavulanate after an initial therapy of two doses of parenteral ceftriaxone . Enrollment criteria included: age 6 months to 5 years, fever > 38.5 degrees C, white blood cell (WBC) count > or = 15,000/ mm3, and lobar/segmental pneumonia on chest radiograph . Twenty-nine patients were randomized to receive oral cefixime and 33 to oral amoxicillin-clavulanate . The two groups were comparable in the following pretreatment parameters: age, duration of illness, temperature, mean WBC count, erythrocyte sedimentation rate, C-reactive protein, and need for hospitalization . Days of resolution of high fever, tachypnea, cough, grunting, and laboratory test abnormalities were similar in the two groups . Clinical response at the end of treatment showed cure, improvement, and failure in 97%, 3%, and 0%, respectively, in the cefixime group and in 88%, 6%, and 6%, respectively in the amoxicillin-clavulanate group (P = NS) . We conclude that young children with community-acquired lobar/segmental pneumonia can be successfully treated with 2 days of parenteral ceftriaxone followed by 8 days of oral cefixime or amoxicillin-clavulanate.

Am J Respir Cell Mol Biol, 1996 Dec, 15(6), 738 - 44
A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion; Tasaka S et al.; Cationic antimicrobial protein of 18 kD (CAP18) was identified and purified from rabbit granulocytes and shown to inhibit various activities of lipopolysaccharide (LPS) . We investigated the effect of a 32-amino-acid C-terminal fragment of CAP18 (CAP18-derived peptide, CDP) on the pathogenesis of acute lung injury caused by intravenous endotoxin . Guinea pigs were divided into six groups: (I) saline control (n = 8), (2) CDP-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5) LPS+CDP10m (n = 8), and (6) LPS+CDP60m (n = 8) . A CDP dose of 0.2 mg/kg was injected at various time points after LPS injection . Lung wet-to-dry weight ratio, {125I}albumin leakage in lung tissue and bronchoalveolar lavage (BAL) fluid, differential cell count in BAL fluid, and histopathologic features were examined 4 h after intravenous administration of 0.02 mg/kg of LPS . The LPS+CDP0m and the LPS+CDP10m groups showed significantly attenuated lung injury compared to that seen in the LPS-alone group, however the LPS+CDP60m group revealed no attenuation of lung injury . The accumulation of peripheral white blood cells into pulmonary vasculature was attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups . We examined the effect of CDP on the expression of adhesion molecules using human umbilical vein endothelial cells, the result of which showed that CDP suppressed the LPS-induced expression of adhesion molecules in a dose-dependent manner . We conclude that CDP attenuates inflammatory cell migration into alveoli resulting in the attenuation of lung injury.

Contraception, 1996 Dec, 54(6), 367 - 72
Synergistic effect of gramicidin and EDTA in inhibiting sperm motility and cervical mucus penetration in vitro; Bourinbaiar AS et al.; Gramicidin, a linear polypeptide with antiviral and antimicrobial properties, was compared in vitro with a commonly used spermicidal detergent-nonoxynol-9 (N9) . The inhibition of sperm functions was evaluated by computer-assisted semen analysis (CASA) for sperm motility, in cervical mucus penetration assay, and by colorimetric tetrazolium salt and lactate dehydrogenase release assays routinely employed for testing the toxicity of drugs . The effective 100% inhibitory concentration (IC100) of gramicidin in a 2-min sperm immobilization assay by CASA was equal to 4 micrograms/ml, whereas IC100 of N9 was equal to 200 micrograms/ml . The presence of 0.1% of chelating agent, EDTA, reduced IC100 of gramicidin to 10 ng/ml, while less than a twofold enhancement in N9 activity was observed upon combination with EDTA . Likewise, the gramicidin/EDTA combination was 100,000 times more potent than N9/EDTA in the sperm penetration assay . Quantitative toxicity tests confirmed that gramicidin is a potent spermostatic rather than spermicidal agent . Further development of a gramicidin/EDTA formulation is warranted as a nontoxic topical contraceptive with activity against viral and microbial sexually transmitted diseases (STDs)PIP: The possibility of enhancing the anti-fertility potential of gramicidin with low doses of ethylenediaminetetraacetic acid (EDTA) was investigated in an in vitro study . The inhibition of sperm functions was evaluated by computer-assisted semen analysis for sperm motility, cervical mucus penetration assay, and colorimetric tetrazolium salt and lactate dehydrogenase release assays . Gramicidin, nonoxynol-9, and EDTA all were found to immobilize sperm, although their effective doses diverged by orders of magnitude . Gramicidin abolished sperm motility within 2 minutes at 4 mcg/ml, but a 50 times higher dose of nonoxynol-9 and 1250 times more EDTA were required to achieve a comparable effect . The combination of 10 ng/ml of gramicidin with 0.1% of EDTA resulted in activity that was four orders of magnitude higher than the optimal combination of nonoxynol-9 with EDTA; sperm penetration into mucus was completely prevented . Moreover, gramicidin inhibited sperm motility without affecting mitochondrial respiratory function or disrupting cell membrane integrity . Quantitative toxicity tests confirmed that gramicidin is a potent spermostatic agent rather than a spermicidal agent . Further development of a gramicidin-EDTA formulation is urged given its potential as a non-toxic topical contraceptive with activity against viral and microbial sexually transmitted diseases .

Am Fam Physician, 1996 Dec, 54(8), 2503 - 12
Fever without source in infants and young children; Daaleman TP; Febrile infants and young children pose a challenge to primary care physicians because the clinical appearance of children who present with fever without source that is related to a viral illness may be similar to the appearance of those with occult bacteremia . The evaluation of the febrile infant and child comprises a comprehensive history, a thorough physical examination and judicious use of laboratory studies . The information derived from this evaluation will help clinicians with the two key management decisions that face physicians caring for this vulnerable population: the initiation and use of antimicrobial therapy, and inpatient versus outpatient management . Although no optimal diagnostic and therapeutic schema exists, physicians should take a structured and rational approach to these patients, depending on their own clinical experience and interpretation of the literature on this topic.

Infect Dis Clin North Am, 1996 Dec, 10(4), 939 - 57
Current perspectives on multidrug-resistant bacteria . Epidemiology and control; Segal-Maurer S et al.; Antimicrobial resistance in bacteria has diminished the availability of effective antimicrobial agents . Knowledge of epidemiology, mechanisms of resistance, and new diagnostic modalities can help to identify and treat patients at risk for infection by these organisms . Limited or nonexistent effective microbial therapy underscores the importance of effective preventive and containment measures.

Infect Dis Clin North Am, 1996 Dec, 10(4), 777 - 96
Fever in the neutropenic host; Chanock SJ et al.; Fever in the neutropenic patient following myelosuppressive chemotherapy is a medical emergency . Appropriate antimicrobial therapy can dramatically reduce infection-related morbidity and mortality . This article reviews the rationale and methodology of treatment as well as its applicability to other neutropenic states . The utility of adjunct therapy with granulocyte- stimulating compounds is also discussed.

Clin Infect Dis, 1996 Dec, 23 Suppl 1, S19 - 24
Pharmacokinetics and pharmacodynamics of newer fluoroquinolones; Stein GE; Newer fluoroquinolones currently under development have excellent pharmacokinetic profiles, and several parameters have been improved compared with those of their predecessors . These compounds are well absorbed, have large volumes of distribution, and distribute into most tissues at concentrations equal to or greater than those observed in serum . Moreover, these newer agents have long serum elimination half-lives that allow for once-daily dosing . With the exception of complexes with multivalent cations that retard absorption, there is a relative lack of clinically significant drug-drug interactions with these antimicrobials . Increased microbiological potency against several important pathogens, along with an enhanced pharmacokinetic profile, will make these newer fluoroquinolones preferable over older compounds for the treatment of a variety of infections.

Clin Infect Dis, 1996 Dec, 23 Suppl 1, S9 - 14
Present studies of therapy for anaerobic infections; Finegold SM et al.; Therapeutic approaches to anaerobic infections are changing . Debridement, drainage, and other surgical approaches remain extremely important . Resistance to antimicrobial agents currently used for treatment of anaerobic infections is increasing . However, promising new agents are being introduced . We review the current status of therapy for anaerobic infections and discuss the potential role of these new agents . We stress an empirical approach to therapy that is based on the usual infecting flora in various types of infections.

Am J Pathol, 1996 Dec, 149(6), 2161 - 7
Cat scratch disease: detection of Bartonella henselae DNA in archival biopsies from patients with clinically, serologically, and histologically defined disease; Scott MA et al.; Serological and epidemiological studies suggest that Bartonella henselae is the etiological agent of cat scratch disease . We designed a study to detect B . henselae in archival biopsies by polymerase chain reaction amplification of the 16S rRNA gene followed by Southern blot hybridization . Forty-two histologically defined cat scratch disease biopsies and eighteen controls were selected for blinded analysis . After testing, charts were reviewed for clinical, immunological, and microbial evidence of infection . Results were correlated with duration of illness and antimicrobial therapy . B . henselae DNA was identified in 27 of 42 (64%) histologically defined patients and 23 of 34 (68%) patients defined both clinically and histologically . There were no false positives (0 of 18) . A small subset (n = 14) had cat scratch disease serological tests performed . B . henselae was identified in 8 of 10 serologically positive patients . Polymerase chain reaction detected 50% of our DNA-positive cases (most of these early in the clinical course) . Southern blotting of amplicons both doubled sensitivity (detecting patients > 4 weeks into illness) and confirmed B . henselae as the causative species . Our study strongly associates B . henselae with cat scratch disease, suggesting that it may be the most likely etiological agent in the majority of patients with cat scratch disease.

Am J Vet Res, 1996 Dec, 57(12), 1714 - 9
Experimentally induced Bartonella henselae infections followed by challenge exposure and antimicrobial therapy in cats; Regnery RL et al.; OBJECTIVES: To elucidate kinetics of Bartonella henselae bacteremia and IgG response, evaluate antibiotic therapy, and investigate challenge exposure in cats . ANIMALS: Specific-pathogen-free cats . PROCEDURE: Cats were inoculated with B henselae or B quintana and monitored . Convalescent cats were challenge exposed with B henselae . Amoxicillin, enrofloxacin, erythromycin, and tetracycline HCl were evaluated for effect on B henselae bacteremia . RESULTS: Cats developed B henselae bacteremia within 1 week; bacteremia persisted for longer than 2 months before subsiding spontaneously . IgG antibody titer developed shortly after onset of bacteremia; antibody co-existed with bacteremia for several weeks and remained detectable after bacteremia subsided . Cats inoculated with B quintana remained abacteremic . On challenge exposure to B henselae, cats previously infected with B henselae remained abacteremic; cats previously inoculated with B quintana supported B henselae infection . Tetracycline HCl and erythromycin depressed B henselae bacteremia; however, duration of bacteremia remained similar to that in untreated cats . Obvious signs of illness were not observed . CONCLUSIONS: Long-duration, high-titer B henselae infections were highly reproducible in cats . Convalescent cats were immune to reinfection . B quintana-inoculated cats did not have evidence of infection and were susceptible to B henselae challenge exposure . Antibiotic therapy was incompletely efficacious in terminating cat bacteremia . CLINICAL RELEVANCE: A cat with an inapparent B henselae infection must provisionally be regarded as a possible reservoir for infection for a minimum of 2 to 3 months . Convalescent cats are resistant to reinfection . Usual antibiotic therapy was not completely efficacious . Measurement of IgG antibody can be used to detect past or current infection.

Am J Forensic Med Pathol, 1996 Dec, 17(4), 343 - 6
Sudden death due to metronidazole/ethanol interaction; Cina SJ et al.; Metronidazole (Flagyl), a commonly prescribed antimicrobial agent, can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol . This drug/chemical interaction results in accumulation of acetaldehyde in the blood . Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic; no lethal serum acetaldehyde level has been established . Sudden death has been reported in patients taking disulfiram while using ethanol; no fatalities have been reported due to ethanol/ metronidazole interactions . Described is a case of a 31-year-old woman who died moments after an assault by a male companion, during which he inflicted minor physical trauma to her upper arm . Toxicologic analysis yielded elevated concentrations of serum ethanol (162 mg/d), acetaldehyde (4.6 mg/d), and metronidazole (0.42 mg/L) . The cause of death was reported to be cardiac dysrhythmia due to acetaldehyde toxicity due to an ethanol/ metronidazole interaction . Autonomic stress associated with the assault is likely to have contributed to this woman's death . The mechanism of death is examined.

Am J Gastroenterol, 1996 Dec, 91(12), 2509 - 12
Evaluation of whole blood antibody kit to detect active Helicobacter pylori infection; Borody TJ et al.; OBJECTIVES: To evaluate the sensitivity and specificity of a whole blood antibody test (Helisal Rapid Blood test) for the detection of Helicobacter pylori using endoscopic diagnostic criteria of histology and urease tests as the "gold standard." METHODS: A prospective trial of Helisal Rapid Blood (HRB) test was carried out in patients undergoing investigations for dyspepsia that included endoscopic biopsy for rapid urease test, microbiological culture, and histology . Blood samples were obtained at the time of endoscopy and were tested for the presence of antibody to H . pylori using the HRB test . In a separate patient group, results of antibody tests in whole venous and capillary blood were compared (n = 25) . RESULTS: The rapid blood test was carried out immediately after the endoscopic examination with a result available in under 10 min in all cases . In 203 patients examined, the HRB test detected 70 of 203 to be H . pylori positive as compared with 71 of 203 using urease/histology . Against combined urease/histology tests, the HRB test achieved 82% sensitivity and 91% specificity . Five patients were judged to be "false negative" on endoscopic tests for H . pylori (extensive intestinal metaplasia n = 3; recent use of antimicrobials) yet the HRB test diagnosed the presence of infection, which could be shown to resolve on treatment . The HRB achieved 89% sensitivity and 91% specificity upon correctly including these five patients in the calculations . In all 25 patients tested, venous and capillary blood results concurred giving HRB test positivity in each case . CONCLUSIONS: Whether using whole venous or capillary blood, the HRB test is a quick, convenient, and accurate test for the diagnosis of active H . pylori infection in patients previously not treated . In a subgroup of patients with low level infection due to recent antimicrobials or intestinal metaplasia negative to all endoscopic tests, the blood test can still correctly diagnose H . pylori infection . Because blood samples require no centrifugation before testing, the greatest usefulness of this test will be that of a primary office diagnostic device.

Ther Drug Monit, 1996 Dec, 18(6), 678 - 87
A liquid chromatography assay for the study of serum and gastric juice metronidazole concentrations in the treatment of Helicobacter pylori; Pollak PT; Metronidazole is an important component of combination antimicrobial therapies used in the eradication of Helicobacter pylori, a recognized cause of gastritis and duodenal ulcer . Studies are needed to understand which pharmacokinetic factors determine the success of metronidazole therapy and what role drug monitoring plays . Such studies require a rapid, accurate assay for small volumes of sample, including gastric juice, over a 200-fold range of concentrations . Using an isocratic high-performance liquid chromatography (HPLC) method, with an 8-min run time and protein precipitation of samples, metronidazole could be measured reliably to as low as 0.5 mg/L in 100 microliters samples of serum, gastric juice, or saliva . Standard curves for serum and gastric juice were linear between 0.5 and 50 mg/L . Within-day coefficients of variation (CVs) (n = 5 at six concentrations) ranged from 1.1 to 4.8% over this range and the between-day CV (n = 7 days) was 5.8% . Neither omeprazole nor common gastroenteric and cardiac medications interfered with this assay . A pilot study, done in four healthy volunteers given intravenous metronidazole 500 mg before and after 7 days of omeprazole therapy, found metronidazole to be present in higher concentrations in gastric juice and saliva than in serum 2 h after intravenous administration . The range and accuracy of the assay proved to be suitable for carrying out pharmacokinetic studies at clinically used doses of the drug.

J Inorg Biochem, 1996 Dec, 64(4), 259 - 71
Zinc, cadmium, and mercury complexes of 5,7-dimethyl-{1,2,4}triazolo{1,5-a}pyrimidine (dmtp) . Preparation, spectroscopic characterization, and biological activity . X-ray crystal structures of {Zn(dmtp)2Br2}, {Hg(dmtp)2Cl2}, and {Hdmtp}2{CdBr4} . 2H2O; Salas JM et al.; The preparation and spectroscopic characterization of a series of dmtp complexes of Zn, Cd, and Hg, where dmtp is 5,7-dimethyl{1,2,4}triazolo{1,5-a}pyrimidine, is reported . Crystal structure analyses of {Zn(dmtp)2Br2} and {Hg(dmtp)2Cl2} reveal distorted tetrahedral geometries about the central atoms and the dmtp ligands to coordinate via the N(3) atom exclusively . In the X-ray structure of {Hdmtp}2{CdBr4}.2H2O, the {Hdmtp}+ cation is protonated at the N(3) atom, there being no significant interaction between Hdmtp and cadmium . A study of the antimicrobial activity of the complexes shows that the {Cd(dmtp)X2(OH2)} (X = Cl, Br) compounds display activity against two strains.

Prim Care, 1996 Dec, 23(4), 793 - 804
Pertussis in primary care practice . Recent advances in diagnosis, treatment, and prevention; Waggoner-Fountain L et al.; Pertussis continues to be an important vaccine-preventable disease . The recent multiple outbreaks of pertussis have heightened interest in its diagnosis, treatment, and prevention . Diagnosis remains challenging, although new diagnostic tests, including enzyme-linked immunosorbent assay of sera and polymerase chain reaction of nasopharyngeal aspirates, offer the possibility of more rapid diagnosis . Erythromycin remains the preferred antimicrobial to reduce secondary transmission of pertussis . The recent approval of acellular pertussis vaccine for the primary series of immunizations ushers in an exciting new era of pertussis prevention.

Schweiz Med Wochenschr, 1996 Nov 30, 126(48), 2078 - 81
{Modifiability of antibiotic use in a medical clinic}; Bogli F et al.; The most costly drug interventions in hospitals are in the treatment of infectious diseases . To improve the cost-effective use of antibiotic drugs it is necessary to consider rational indications, appropriate administration (sequential therapy) and control of antimicrobial resistance . To obtain more information about prescribing habits, antibiotic prescription forms were collected prospectively over a six-month period in the Clinic of Internal Medicine at the Cantonal Hospital of Aarau . The influence of this new prescription form on antibiotic use, including the indication for therapy, was analyzed and compared with the results of a similar study done in 1994 . The results showed use of a wide variety of different antibiotics for the same indication, prevalence of intravenous administration, and widespread use of new and expensive antibiotics . The total cost of antibiotics was not reduced compared with the previous period . The characteristics of antibiotic use were easily analyzed with minimal additional effort . With such data, specific actions for quality improvement in antibiotic use can be taken through a multidisciplinary educational approach with regular instruction on therapy guidelines, definition of first-line agents, information on the advantages of sequential therapy, and periodic reevaluation.

FEBS Lett, 1996 Nov 25, 398(1), 87 - 90
Solution structure of an antimicrobial peptide buforin II; Yi GS et al.; The structure of 21-residue antimicrobial peptide buforin II has been determined by using NMR spectroscopy and restrained molecular dynamics . Buforin II adopts a flexible random structure in H2O . In trifluoroethanol (TFE)/H2O (1:1, v/v) mixture, however, buforin II assumes a regular alpha-helix between residues Val12 and Arg20 and a distorted helical structure between residues Gly7 and Pro11 . The model structure obtained shows an amphipathic character in the region from Arg5 to the C-terminus, Lys21 . Like other known cationic antimicrobial peptides, the amphipathic structure might be the key factor for antimicrobial activity of buforin II.

FEBS Lett, 1996 Nov 25, 398(1), 74 - 80
Structural, functional analysis and localization of the human CAP18 gene; Larrick JW et al.; CAP18 is an antimicrobial protein found in specific granules of PMNs . The human CAP18 (HCAP18) gene was cloned from a human genomic phage library . Sequence analysis revealed the HCAP18 gene to have 4 exons spanning 3 kb, including 700 bp of upstream DNA . Using 3' RACE no homologs of human HCAP18 were found in human bone marrow or leukocyte populations . By PCR analysis of a somatic cell mapping panel and fluorescence in situ hybridization of a genomic clone to metaphase chromosomes the gene was mapped to chromosome band 3p21.3 . Like several other genes expressed late in PMN development the CAP18 gene did not contain typical TATA box or CCAAT sequences . Expression in Cos 7 cells permitted limited mapping of the promoter function in upstream fragments of the HCAP18 gene . Western blot, Northern blot and RT-PCR analysis show HCAP18 to be produced specifically in granulocytes . This work forms the groundwork for future analysis of the genetic regulation of this antimicrobial protein during PMN differentiation.

Vet Rec, 1996 Nov 23, 139(21), 519 - 21
Discospondylitis in an adult horse; Hillyer MH et al.; Discospondylitis, of presumed bacterial origin, was diagnosed in an adult thoroughbred racehorse . The clinical signs were vague and associated with abnormal mobility of the neck and forelimbs . Clinical pathology showed only a non-specific inflammatory response . A scintigraphic examination revealed the site of the lesion and the diagnosis was confirmed by the identification of radiographic changes affecting two thoracic vertebrae . A prolonged course of antimicrobial agents produced a complete recovery and the horse returned to full athletic use.

J Biol Chem, 1996 Nov 22, 271(47), 29537 - 44
Characterization of novel cysteine-rich antimicrobial peptides from scorpion blood; Ehret-Sabatier L et al.; We have isolated, from the hemolymph of unchallenged scorpions of the species Androctonus australis, three distinct antimicrobial peptides, which we have fully characterized by Edman degradation, electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry . Two are novel molecules: (i) androctonin, a 25-residue peptide with two disulfide bridges, active against both bacteria (Gram-positive and Gram-negative) and fungi and showing marked sequence homology to tachyplesins and polyphemusins from horseshoe crabs; and (ii) buthinin, a 34-residue antibacterial (Gram-positive and Gram-negative) peptide with three disulfide bridges . The third peptide contains 37 residues and three disulfide bridges and clearly belongs to the family of anti-Gram-positive insect defensins . We have synthesized androctonin and explored its activity spectrum and mode of action.

J Am Vet Med Assoc, 1996 Nov 15, 209(10), 1753 - 5
Oxytetracycline residues in milk after intrauterine treatment of cows with retained fetal membranes; Dinsmore RP et al.; OBJECTIVE: To establish the maximum concentration and duration of oxytetracycline residues in milk from cows with retained fetal membranes given the antimicrobial via intrauterine infusion, and to investigate whether the number of infusions or the presence of fever (> 39.7 C) affected the duration of residues . DESIGN: Prospective study . ANIMALS: 54 Holstein cows with retained fetal membranes on a single 1,400-cow commercial dairy . PROCEDURE: Cows were treated once a day with 5 g of oxytetracycline (50 ml of 100 mg/ml solution in a povidone base) by intrauterine infusion for at least 2 days, or until the membranes were expelled . Cows that became febrile (rectal temperature > or = 39.7 C) were also given 20,000 IU of procaine penicillin G/kg of body weight, i.m., for 2 to 4 days . Milk samples were collected at 24-hour intervals during treatment . and at 12-hour intervals after the last treatment . All samples were frozen and submitted every 2 weeks for high performance liquid chromatography analysis for oxytetracycline . RESULTS: Oxytetracycline was detected in milk of all cows during treatment, at a maximum concentration ranging from 47.2 to 1,804.6 micrograms/kg (mean, 316.9 micrograms/kg) . Duration of oxytetracycline residues after the last infusion ranged from 0 to 144 hours (mean, 52.3 hours) . Neither the number of infusions received, nor development of rectal temperature > 39.7 C, affected the maximum concentration or the duration of oxytetracycline residues in milk . CLINICAL IMPLICATIONS: Milk obtained from cows that had been treated for retained fetal membranes by intrauterine infusion of oxytetracycline should be discarded to avoid illegal residues.

Pharmacoeconomics, 1996 Dec, 10(6), 575 - 93
Rational prescribing of antibacterials in hospitalised children; Hoppe JE; The subject of this review is the rational prescribing of antimicrobial agents for the therapy of serious community-acquired infections in hospitalised infants and children . First, cost-containment strategies such as streamlining of antibacterial therapy, outpatient parenteral antibacterial therapy and sequential ('stepdown') therapy with parenteral followed by oral therapy are reviewed . In most of these areas, paediatric studies are scant or lacking . Then specific paediatric aspects of the choice of parenteral antibacterials such as penicillins, cephalosporins, aminoglycosides, macrolides and other agents are discussed . With particular reference to cost containment, rational treatment strategies for some serious bacterial infections such as meningitis, occult bacteraemia, endocarditis, osteomyelitis, arthritis, pyelonephritis, Lyme borreliosis (advanced stages) and pneumonia are proposed . In most of these disease, there is potential for cutting treatment costs and studies that compare these newer strategies with traditional treatment regimens are urgently needed.

Vestn Otorinolaringol, 1996 Nov-Dec, (6), 18 - 9
{Endoprosthesis of the frontonasal anastomosis after extranasal radical operations using biocompatible tubular polymeric materials}; Klochikhin AL et al.; The authors present pilot experience of extranasal radical operations on the frontal sinuses with the use of polymeric tube endoprostheses made of biocompatible polymeric materials EFOS 1, 2, 3 containing antimicrobial drugs (dioxidin, chinoxidin) and active substances promoting regeneration and epithelization (orotic acid derivatives) . The above technique was employed in operations on frontal sinuses in 12 patients . Polymeric endoprostheses EFOS provide adequate lumen of the formed frontonasal anastomosis, reduce the occurrence of postoperative complications and recurrences as well as hospital stay.

Rozhl Chir, 1996 Nov, 75(11), 544 - 8
{Cefoperazone in the treatment of infections of the gallbladder, biliary ducts and liver in surgical patients}; Vyhnanek F et al.; In 20 patients treated on account of advanced cholecystitis, inflammations of the biliary pathways and liver a cephalosporin of the third generation, cefoperazone, was administered within the framework of antimicrobial treatment after surgery or after endoscopic intervention . In the laboratory investigation of the study in isolated bacteria minimal inhibitory concentrations and serum, biliary and tissue levels of cefoperazone were assessed . The minimal inhibitory concentrations in the assessed bacteria were several times lower than the levels assessed in serum, bile and the wall of the gallbladder . The infection was eradicated in 20 patients . Seventeen patients were cured (85%).

Indian Heart J, 1996 Nov-Dec, 48(6), 677 - 80
Reuse of pacemaker; Panja M et al.; Implantation of a permanent pacemaker is an expensive proposition for the poor patients of our country . Many patients on permanent pacemaker die prematurely due to diseases or conditions not related to pacemaker function . The purpose of this study was to reuse these pacemakers after thorough cleansing and proper sterilisation in other suitable patients and compare the efficiency of the reused pacemakers with that of newly implanted ones . Between April 1979 and April 1992, 642 patients implanted with reused pacemakers were studied . The study population consisted of patients ranging in age from 15-85 years and included patients of both sexes (M:F = 4:1) . The mean period of follow-up was 7.5 +/- 5.6 years . Removal and reimplantation of the pulse generators was carried out after obtaining the State Government's approval, informed consent of the donors, relatives and recipients . The functional status of the pulse generators was tested by a "pacing system analyser" . The clinical indications for reuse were chronic complete heart block, symptomatic bifascicular heart block, sick sinus syndrome and chronic complete heart block with congestive heart failure, in decreasing order of frequency . In terms of morbidity and mortality, the efficacy of reused pacemakers was highly comparable with that of newly implanted ones . The infection rate in cases of reuse from dead patients was comparable to that in cases of new implantation . However, pacemakers reused in the same patient showed a high rate of infection . With the aid of newer generations of antimicrobials, infection when matched with efficacy and economy (of reuse) does not seem to be a major factor against pacemaker reuse.

Ann Acad Med Singapore, 1996 Nov, 25(6), 797 - 803
Bronchoscopy in immunocompromised host with pulmonary infiltrates; Hsu AA et al.; Pulmonary complications related to immunosuppression may be secondary to infection, neoplasia, toxic effects of chemotherapy and radiotherapy or the primary disease itself . The diagnostic yield from bronchoscopic studies on immunocompromised hosts (ICH) with pulmonary infiltrates varies widely and the indication and timing for bronchoscopic procedures remain uncertain . We prospectively studied 60 consecutive ICH with pulmonary lesions over a 12-month period . Bronchoscopic studies were performed as soon as pulmonary lesions were detected and within 72 hours of antimicrobial treatment . The patients were divided into two groups: E (40 patients) and L (20 patients) were bronchoscoped on average 1.6 days (SD 0.8) and 16.7 days (SD 10.8) respectively after clinical detection and antimicrobial treatment . A total of 131 bronchoscopic procedures were performed . These included bronchoalveolar lavage 60, bronchoscopic lung biopsy 47, bronchial biopsy 8, brushing 8 and washing 8 . Diagnostic yields for bronchoscopically obtained fluid and tissue histology were 45% and 49% respectively . Both complement each other resulting in a higher diagnostic yield of about 70% of the patients in both groups . Procedural complications were minor (13% of cases) and mortality was zero . Infections accounted for approximately two-thirds of the pulmonary lesions . Patients bronchoscoped earlier received less antimicrobial empiric therapy and had shorter hospitalisation . Despite delayed bronchoscopy in ICH in the late group, bronchoscopic results influenced in 85% of patients . However, based on earlier use of appropriate therapy, shorter hospitalisation and decreased costs, we recommend early bronchoscopy when response to empiric treatment has been unsatisfactory.

Anticancer Res, 1996 Nov-Dec, 16(6B), 3901 - 5
The clinical applications of granulocyte colony-stimulating factor in hematopoietic stem cell transplantation: a review; Tabbara IA et al.; The administration of recombinant human granulocyte colony-stimulating factor (G-CSF) following chemotherapy, has been shown, in controlled randomized trials, to decrease the incidence of febrile neutropenic episodes, the duration of severe neutropenia and intravenous antimicrobial therapy, and the length of hospitalization . This review focuses on the evolving role of G-CSF in bone marrow and peripheral blood stem cell transplantation, and in hematopoietic stem cell mobilization.

Dev Comp Immunol, 1996 Nov-Dec, 20(6), 427 - 39
Deactivation of primed respiratory burst response of goldfish macrophages by leukocyte-derived macrophage activating factor(s); Neumann NF et al.; Macrophage activation factors (MAF), induced maximal priming of the respiratory burst response in GMCL after 6 h of stimulus, but by 24 or 48 h no priming effect was observed . Bacterial lipopolysaccharide (LPS) also primed the respiratory burst of goldfish macrophages, but the kinetics of priming were different from that induced by MAF . LPS induced a gradual increase in priming potential over 48 h of cultivation . Co-stimulation of macrophages with MAF and LPS resulted in enhanced priming of respiratory burst activity compared to either factor alone; however, the kinetics of priming were similar to those induced by MAF only . The MAF antagonized the ability of LPS to prime the respiratory burst over extended cultivation . The priming kinetics of the respiratory burst induced by MAF and/or LPS were not unique to GMCL, but were also similar for primary cultures of IVDKM . Respiratory burst deactivated macrophages-mounted potent nitric oxide response, indicating that this deactivation event was selective for respiratory burst activity . Autocrine factors produced by MAF-activated macrophages augmented priming of the respiratory burst, suggesting that deactivation of primed respiratory burst responses was not due to cytokine mediators produced by activated macrophages, but was most likely an intracellular deactivation event . Furthermore, production of reactive intermediates by activated fish macrophages was biphasic; with maximal ROI production occurring 6 h after stimulus, and maximal RNI occurring 72 h after stimulus . Our results indicate that activated fish macrophages mount sequential antimicrobial responses that are selectively deprogrammed once maximal induction has occurred . The ability to selectively deactivate ROI production without affecting subsequent RNI production may play an important role in host defense: regulating the duration of ROI production, and thus minimizing host tissue damage in an otherwise futile attempt to eliminate ROI resistant pathogens.

PDA J Pharm Sci Technol, 1996 Nov-Dec, 50(6), 352 - 5
Use of the green fluorescent protein to rapidly assess viability of E . coli in preserved solutions; Casey WM et al.; E . coli strain HB101 was genetically engineered to a fluorescent phenotype by transformation with a plasmid containing complementary DNA for a green fluorescent protein . The level of fluorescence in the transformed strain was directly proportional to the number of viable cells . There was a rapid decrease in fluorescence when transformed cells were inoculated into lamivudine solutions containing ten different preservative formulations . The decrease in fluorescence correlated to a decrease in the number of viable cells, allowing the relative antimicrobial properties of each solution to be compared . This methods provides a simple, rapid (< 2 min/assay), and accurate means of determining the effects of antimicrobial solutions on the viability of E . coli.

Farmaco, 1996 Nov, 51(11), 757 - 60
Synthesis and antimicrobial assays of 3-diazoindole-2-carboxamides; Garuti L et al.; Some 3-diazoindole-2-carboxamides have been synthesized and their antimicrobial activity have been tested . Antimicrobial activity was practically lacking.

Farmaco, 1996 Nov, 51(11), 707 - 13
Biological studies on 1,2-benzisothiazole derivatives VI Antimicrobial activity of 1,2-benzisothiazole and 1,2-benzisothiazolin-3-one derivatives and of some corresponding 1,2-benzisoxazoles; Zani F et al.; Numerous 1,2-benzisothiazole and 1,2-benzisothiazolin-3-one derivatives, variously substituted in the different positions of the molecule, were tested for their in vitro antimicrobial activity . Some corresponding 1,2-benzisoxazoles and 1,2-benzisoxazolin-3-ones were also considered . Several compounds possess a potent and broad antibacterial and antifungal activity, particularly against Gram positive microorganisms, yeasts and dermatophytes . 1,2-Benzisothiazolin-3-ones were found to be the most active substances . On the contrary, the benzisoxazoles and the benzisoxazolin-3-ones considered were devoid of activity . The results obtained are discussed on the basis of structure-activity relationships.

Z Naturforsch {C}, 1996 Nov-Dec, 51(11-12), 807 - 12
Localization of benzoxazinones that occur constitutively in wheat seedlings; Iwamura H et al.; Occurrence and localization of novel antimicrobial and antifeeding compounds in wheat, 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and their glucosides, were examined by staining wheat plants (Triticum aestivum L.) in the juvenile stage of growth by ferric chloride . The methanol extracts of the stained plant tissues gave a characteristic blue color, which was shown by spectroscopic and chromatographic analyses to be exclusively due to benzoxazinones . When ferric chloride was applied to the root in the seedlings, the blue color immediately developed, the staining being strongest at the tip region and becoming lighten towards the basal part . The staining pattern of the radicle in the pre-emerging seed was similar to that in the root, but the coleorhiza was not stained . Little staining was observed in the epidermal layer of the leaf sheath in the shoot but the underlying tissue was stained strongly . The foliage leaf folded in the sheath was also stained, but less intense than the shealth tissue . It is suggested that the DIBOA and DIMBOA are produced within the stained region of the leaf and root . Together with previous findings that the benzoxazinones appear constitutively in wheat during the juvenile stage of growth . their localized occurrence in the tissues exposed to microbial and insect attacks suggests that they act as defense compounds during this vulnerable plant stage.

Semin Liver Dis, 1996 Nov, 16(4), 357 - 67
Mechanisms of liver damage; Losser MR et al.; The liver is implicated in many processes, and its failure induces severe consequences for metabolism, immune response, detoxification and antimicrobial defenses . The mechanisms involved in liver injury are complex and interactive, and can be artificially separated as chemical and immune injuries . The biochemical mechanisms concern various chemicals that are detoxified in the liver via cytochrome P-450 and conjugation . Toxic metabolites may alter plasma membrane, mitochondria, intracellular ion homeostasis, or degratative enzyme activity . Immune mechanisms involve cell cooperation, and are mediated by cytokines, nitric oxide, and complement . Pathologic apoptosis is potentially an important mechanism of acute liver injury . Specific attention is paid here to the more frequent causes of acute liver failure: hypoxia/reoxygenation, liver congestion, acetaminophen poisoning, posttransplant acute liver rejection, severe sepsis, viral hepatitis, and alcoholic liver disease . Knowledge of the intimate mechanisms of liver injury at the cellular level may lead to adaptation of therapeutic strategies that will prevent end-stage liver failure.

Rev Mal Respir, 1996 Nov, 13(5 Suppl), S71 - 84
{Lung complications of hematopoietic stem cell transplantation}; Philit F et al.; Bone marrow transplantation (BMT) is a potentially curative therapy in selected patients with hematologic disorders (acute leukemia, chronic myelogenous leukemia, lymphoma) or solid tumors (testicular or breast cancer) . Pulmonary complications occur in 40 to 60% of patients receiving BMT, and are related to various mechanisms: chemotherapy-induced neutropenia, pulmonary toxicity of radiotherapy or chemotherapy, graft-versus-host disease . Bacterial or fungal pneumonia occurring during the initial period of neutropenia, and interstitial pneumonia (related to cytomegalovirus or of unknown origin) are the major respiratory complications of the first 100 days . Bacterial sinusitis and pulmonary infections, and obstructive airways disease related to bronchiolitis are the main late-onset respiratory disorders . No single risk factor can predict the development of these complications, which result from a sequence of events including infections, pulmonary injuries related to chemotherapy or radiotherapy, and inappropriate immunological reaction after transplantation . Antimicrobial prevention has been shown to reduce the mortality of these complications, but they still result in both important morbidity and mortality . They are the most frequent non relapse cause of death among long term surviving patients . Better understanding of their pathogenesis, and early recognition and treatment of respiratory complications of BMT should improve the efficacy of this therapy.

Prikl Biokhim Mikrobiol, 1996 Nov-Dec, 32(6), 615 - 9
{Preparation of fiber materials containing both the immobilized proteolytic enzyme and antimicrobial substance, and study of their properties}; Virnik AD et al.; Properties of joint immobilization of a proteolytic enzyme (terrilytin, trypsin, collytin, or protease C) and an anti-microbe compound to cellulose copolymer containing carboxyl groups were investigated . It was established that the molecule of anti-microbe substance containing a few base groups enhanced stability of the enzyme immobilized, most likely due to additional fixation of the enzyme macromolecule . Changes in activity of the materials containing both protease and anti-microbe compound were studied upon gamma-sterilization and subsequent prolonged storage . The materials with combined biological action were demonstrated to accelerate markedly wound cleansing and healing.

Pathology, 1996 Nov, 28(4), 366 - 9
Vancomycin and amikacin in cell cultures for virus isolation; Lo JY et al.; Contamination of cell cultures for virus isolation has been increasingly encountered . By reviewing and changing the antimicrobials incorporated in cell culture media, we aim to control this problem . Contaminated cell culture fluids were inoculated for bacterial and fungal isolation, identification and antibacterial susceptibility testing . Based on the above results, vancomycin and amikacin were chosen to replace the penicillin and gentamicin used conventionally . Analysis was carried out on various characteristics of cell culture with respect to antimicrobial change . All contaminating Gram-positive bacteria were susceptible to vancomycin while about 80% of the Gram-negative bacteria were sensitive to amikacin . The new antimicrobial combination was not toxic to cell cultures and both antimicrobials were found to remain stable in media for over six months . The virus isolation rate was maintained after antimicrobial change while the contamination rate was reduced from nearly 10% to 1.5% . We thus conclude that vancomycin and amikacin can well replace the conventional penicillin and gentamicin to be incorporated into maintenance and transport media to control the emerging problem of viral culture contamination.

Infection, 1996 Nov-Dec, 24(6), 480 - 4
Empirical monotherapy with meropenem versus imipenem/cilastatin for febrile episodes in neutropenic patients; Shah PM et al.; In a nonblind, randomised, parallel-group study, initial empirical monotherapy with meropenem 1 g intravenously every 8 h was compared to an identical dosage of imipenem/cilastatin for the treatment of 66 febrile episodes in 61 adult neutropenic patients . 25/31 episodes treated with meropenem and 24/30 imipenem/cilastatin-treated episodes were still receiving unmodified therapy at 72 h (primary endpoint); this difference was not statistically significant . By the end of the treatment courses, 18/31 meropenem-treated episodes had responded clinically (cured or improved) compared with 18/30 episodes treated with imipenem/cilastatin . Another ten episodes initially treated with meropenem and six episodes treated with imipenem/cilastatia were cured after an additional antimicrobial agent had been administered (cured with modification) . Satisfactory bacteriological responses (eradication plus presumed eradication) at the end of unmodified therapy was 9/11 in the meropenem group and 14/16 in the comparator group . Both regimes were well tolerated; however, there were more reports of nausea and/or vomiting in the impenem/cilastatin group (7/33 vs . 2/33 in the meropenem group) . The carbapenems meropenem and imipenem/cilastatin appear to be suitable agents for empirical monotherapy of febrile episodes in neutropenic patients . Meropenem may be better tolerated than imipenem/cilastatin, allowing optimal dosing in this patient population.

Nucl Med Biol, 1996 Nov, 23(8), 995 - 8
18F-labeling and biodistribution of the novel fluoro-quinolone antimicrobial agent, trovafloxacin (CP 99,219); Babich JW et al.; {18F}CP 99,219 {(1 alpha, 5 alpha, 6 alpha)-7-(6-amino-3-azabicyclo {3.1.0}hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid} was prepared by 18F for 19F exchange followed by reverse-phase HPLC purification . Studies of the effects of reaction time and temperature on 18F incorporation demonstrated that heating 1.0 mg of CP 99,219 in 0.5 cc of DMSO with 4.5 mg of K2CO3 and 24 mg of Kryptofix for 15 min at 160 degrees C results in the optimal compromise between radiochemical yield and purity . This method routinely provides radiochemical yields of 15-30% {EOS} with radiochemical purities of > 97% . Varying the concentration of CP 99,219 in the reaction mixture had no effect on yield . Biodistribution studies in rats demonstrated that significant concentrations of drug accumulate in most tissues . The tissues with the highest concentrations of drug were intestine, liver, kidney, and stomach.

Clin Ther, 1996 Nov-Dec, 18(6), 1128 - 38
Clinical efficacy of dirithromycin in patients with bacteremic pneumonia; Hernandez JM et al.; Dirithromycin is a new macrolide antimicrobial drug with a long half-life (44 hours) that reaches high tissue concentrations, thus permitting once-daily oral dosing and shorter courses of therapy . Soon after absorption, dirithromycin enters the tissue so rapidly that serum concentrations are comparatively low . It could be hypothesized that these low serum levels could endanger the outcome in patients with bacteremic pneumonia . We reviewed the database on dirithromycin pneumonia (consisting of 1108 patients randomized to receive dirithromycin or erythromycin in two double-masked trials) to ascertain its efficacy in patients with community-acquired pneumonia and concomitant bacteremia . Fourteen (2.5%) of 555 dirithromycin-treated patients and 10 (1.8%) of 553 erythromycin-treated patients had bacteremia . A favorable clinical response posttherapy was observed in 92.3% and 88.9% of these patients with a response assigned, respectively . Overall, favorable response rates were comparable between the two groups in the bacteremic subsets: patients with pneumococcal bacteremia, patients with nonbacteremic pneumococcal pneumonia, and all patients enrolled with acute pneumonia who had a posttherapy clinical response . In the treatment of patients with mild or moderate community-acquired pneumonia, including those with unsuspected and incidental bacteremia, dirithromycin is an effective macrolide antimicrobial drug.

Health Bull (Edinb), 1996 Nov, 54(6), 499 - 504
Audit on the use of prophylactic parenteral antimicrobial agents and the use of co-amoxiclav and metronidazole; Redding PJ et al.; Following the recommendations of a previous audit, specific objectives were chosen for reaudit . The aim was to measure the adherence to agreed protocols for the use of prophylactic antimicrobial agents; including the use of the once only part of the Kardex and to measure the adherence to protocols for the use of parenteral co-amoxiclav and metronidazole . The audit was conducted in the same hospital as the original study . Data was collected for one month on all patients receiving prophylactic antimicrobial agents, parenteral co-amoxiclav or metronidazole . A microbiologist assessed the compliance to the agreed written protocols, which had been distributed and explained to each resident . One hundred and eighty-eight patients received 226 antimicrobial courses (649 doses) . Seventy-two per cent of courses were considered appropriate compared with 65% in 1993 . The criteria for this audit only allowed one cephalosporin choice per directorate and accounted for the inappropriateness of choice to be 19% compared with 12% in 1993 . This was confined to one directorate and an overall improvement of 79% would have been achieved if any cephalosporin could be chosen as 1993 . Eighty-two per cent of doses were considered appropriate if written in the once only part of the Kardex or the anaesthetic sheet compared with 51% of those written in the general part . Only nine per cent of courses were too long compared with 16% in 1993 . Fifty seven patients were given 125 days of co-amoxiclav, 94 days for treatment and 31 days for prophylaxis . Co-amoxiclav use overall was 33% less than 1993 with an improvement of appropriateness from 30% to 68% . CONCLUSIONS: An overall improvement in the appropriateness of prophylactic antibiotic use was achieved by the implementation of agreed protocols . An automatic stopping system reduced the continuation of prophylaxis.

Kansenshogaku Zasshi, 1996 Nov, 70(11), 1181 - 5
{Invasive pulmonary aspergillosis caused by aspiration of polluted water after nearly drowning}; Mizukane R et al.; A 21-year-old male nearly drowned in a reservoir by a traffic accident and he aspirated a large mount of polluted water containing Aspergillus fumigatus . On admission to our hospital, he was alert but cyanotic . Chest rentogenograms showed scatter infiltrative shadows in bilateral lung fields . We administered methylpredonizolon and antimicrobial agents immediately because of respiratory failure which was rapidly progressing . During the following six days, infiltrative shadows diminished but multiple nodular shadows in both lung fields appeared . The diagnosis of pulmonary aspergillosis was confirmed by serological and microbiological studies . Intravenous amphotericin B and oral itraconazol were administrated, and clinical improvement was observed.

Ther Umsch, 1996 Nov, 53(11), 854 - 62
{Empirical antimicrobial therapy in neutropenic patients}; Maschmeyer G; Infectious complications emerge in more than 80% of neutropenic patients after intensive antineoplastic therapy . Empirical antimicrobial intervention is mandatory, and initial administration of an antipseudomonal betalactam in combination with an aminoglycoside represents the most widely applied standard regimen . At least in patients with short-term neutropenia, also an initial betalactam monotherapy is accepted . Symptoms of skin or venous-catheter-related infection should prompt the addition of a glycopeptide, whereas in case of lung infiltrates, amphotericin B should be administered at least after 96 h . of nonresponse to the antibiotic first-line therapy . In nonresponders with persisting fever of unknown origin, carbapenems or fluoroquinolones in combination with a glycopeptide might be considered for second-line treatment . The supplementation of a recombinant hematopoietic growth factor {G-CSF or GM-CSF} shows no significant benefit and should be restricted to controlled clinical studies . In case of good clinical response, the established antimicrobial treatment regimen should be continued for at least seven days in persistently neutropenic patients.

J Antibiot (Tokyo), 1996 Nov, 49(11), 1105 - 9
Exophilin A, a new antibiotic from a marine microorganism Exophiala pisciphila; Doshida J et al.; Exophilin A, a new antibacterial compound, was discovered in the culture of the marine microorganism Exophiala pisciphila NI10102, which was isolated from a marine sponge Mycale adhaerens . The absolute chemical structure of exophilin A was elucidated as a trimer of (3R,5R)-3,5-dihydroxydecanoic acid by spectroscopic methods and analyses of a degradative product . Exophilin A showed antimicrobial activity against Gram-positive bacteria.

J Antibiot (Tokyo), 1996 Nov, 49(11), 1091 - 5
Madindoline, a novel inhibitor of IL-6 activity from Streptomyces sp . K93-0711 . I . Taxonomy, fermentation, isolation and biological activities; Hayashi M et al.; Selective growth inhibition against IL-6-dependent cells was detected in fermentation extracts of a microbial strain, K93-0711, which was characterized as Streptomyces species . Active metabolite, termed madindoline A and B, were isolated, and the structure was determined to be 3a-hydroxy-indoline with diketocyclopentene at the N position . Madindoline A and B displayed dose-dependent inhibition of MH60 cells, an IL-6-dependent cell line, in presence of 0.1 U/ml IL-6 . The IC50 for madindoline A and B against this cell line was 8 microM and 30 microM, respectively . These compounds did not inhibit the growth of cell lines which are not IL-6 dependent and the growth inhibition of the MH60 cell line was reversed by addition of excess, 0.4 U/ml, of IL-6 to the culture media . These compounds did not show any antimicrobial activity at a concentration of 1,000 micrograms/ml.

Hepatogastroenterology, 1996 Nov-Dec, 43(12), 1656 - 9
Detection of Helicobacter pylori infection using single serum specimens: comparison of five commercial serological tests; Allerberger F et al.; BACKGROUND/AIMS: Various commercial kits have been developed for serological diagnosis of Helicobacter pylori infection, but data on their diagnostic accuracy and direct comparisons between the tests are often lacking . We evaluated the sensitivity, specificity and relative agreement of three assay kits which have not been evaluated in published studies so far . MATERIAL AND METHODS: We examined a self-contained card-based enzyme immunoassay (ImmunoCardR H . pylori IgG; Meridian Diagnostics, Milano, Italy), a microwell-based enzyme immunoassay (Enzygnost Anti-Helicobacter pylori/IgG; Behringwerke, Marburg, Germany), and an indirect immunofluorescence test (Immunfluoreszenz IgG Test; Bios, Graefelfing, Germany) . We also examined a latex agglutination test (PylorisetR Dry; Orion Diagnostica, Espoo, Finland) and a complement fixation test (CFT H . pylori; Institute Virion, Rueschlikon, Switzerland) which have been evaluated by others previously . Sera originated from 110 patients, sent to the outpatient clinic of a large tertiary hospital for gastrointestinal endoscopy . RESULTS: We found that the latex agglutination test, card-based enzyme immunoassay, and microwell-based enzyme immunoassay had overall sensitivities of 74.4%, 95.4%, and 90.7%, and specificities of 94%, 76.1%, and 79.1% respectively . Indirect immunofluorescence test and complement fixation test yielded sensitivities/specificities of 62.8%/86.6%, and 74.4%/77.6%, respectively, when compared with gastric biopsy findings . Combining two tests did not increase the diagnostic yield . The relative agreement of the latex test, card-based enzyme immunoassay, microwell-based immunoassay, immunofluorescence test, and complement fixation test was 86.4%, 83.6%, 83.6%, 77.3%, and 76.4%, respectively . CONCLUSIONS: We conclude that for serology based on single serum specimens the enzyme immunoassays and the commercial latex test represent helpful noninvasive tools for the diagnosis of Helicobacter pylori infection . Complement fixation test and IIFT might be more suitable for serological tests on multiple serum specimens, e.g . monitoring the effect of antimicrobial eradication therapy.

J Matern Fetal Med, 1996 Nov-Dec, 5(6), 355 - 8
Septic pelvic thrombophlebitis or refractory postpartum fever of undetermined etiology; Witlin AG et al.; The objective of this study was to review and characterize the presentation, diagnostic dilemmas, management, and prognosis of postpartum septic pelvic thrombophlebitis . Medical records of postpartum women with the diagnosis of septic pelvic thrombophlebitis were reviewed for the 8-year period 1986-1994 . Cases of documented ovarian vein thrombosis or those with other pelvic pathology on imaging study were excluded . Thirty-one women, four following vaginal delivery and 27 following cesarean delivery, with a final diagnosis of septic pelvic thrombophlebitis were identified . All patients demonstrated refractory febrile morbidity (mean 5.5 +/- 1.9 days prior to instituting heparin therapy) despite multiagent antimicrobial therapy with ampicillin, gentamicin, and clindamycin . Imaging studies (CT and/or ultrasound) were performed in 20 women and revealed no pelvic pathology . The patients required an average of 4.7 +/- 2.1 days (median 5, range 1-9 days) of heparin therapy before defervescence . Heparin levels were therapeutic at a mean of less than 24 h (range 6-24 h) . The average dose of heparin required was 16.0 +/- 3.0 U/kg/h . Nine women had 13 subsequent pregnancies without recurrent thromboembolic complications . Currently available imaging studies cannot diagnose the entity we now define as septic pelvic thrombophlebitis (once cases of ovarian vein thrombosis are excluded) . Our findings do not support the time-honored rule that septic pelvic thrombophlebitis responds within 24-48 h to therapeutic anticoagulation with heparin . Therefore, criteria other than imaging studies or immediate defervescence following heparin therapy are necessary for diagnosis of septic pelvic thrombophlebitis . A more appropriate terminology for septic pelvic thrombophlebitis should be refractory postpartum fever of undetermined etiology.

J Pharm Pharmacol, 1996 Nov, 48(11), 1201 - 5
Study of interaction effects of polyacrylic acid polymers (carbopol 940) on antimicrobial activity of methyl parahydroxybenzoate against some gram-negative, gram-positive bacteria and yeast; Scalzo M et al.; Cosmetic or pharmaceutical formulations containing hydrophilic polymers of natural or synthetic origin, may be more exposed to successful microbial contamination because of a polymer-preservative interaction . The experimental data reported in this paper relate to the possible interference of Carbopol 940 with methyl parahydroxybenzoate . Results show that this hydrophilic polymer, widely employed in many formulations, exerts, on the contrary, an interesting synergism on microbicidal activity of the preserving agent against E . coli and P . Aeruginosa . A reduction in microbicidal activity against S . aureus and C . albicans is observed for a polymer concentration higher than that needed for anti-Gram-negative synergy.

J Antimicrob Chemother, 1996 Nov, 38(5), 895 - 904
Trends in hospital antibiotic prescribing after introduction of an antibiotic policy; Gould IM et al.; Trends in antibiotic prescribing in Grampian were monitored prospectively for seven years from 1986 using computerised ward stock lists and laboratory data relating to all in-patient and out-patient treatments in all Grampian hospitals serving a population of 500,000 . The main outcome measures were the number of antibiotics available for routine and restricted uses, annual expenditure and defined daily doses (DDDs) of high expenditure antimicrobial agents . An antibiotic committee introduced a policy and formulary in the third year of the study which had only limited success in controlling prescribing . During the period of the study 30 new antibiotics were considered for inclusion in the hospital formulary, but only seven were incorporated, and all for restricted use only . Despite this, expenditure on antibiotics has more than doubled since 1986, two thirds of the increase being due to the use of new drugs . There was also an increased use of older antibiotics (DDDs increased by 33%), often for no clear reasons, and an overall increase of 46% in DDDs . Antibiotics have increased from 11.9-18.7% as a proportion of the drug budget . These findings highlight the current difficulty in controlling prescribing budgets, the increasing use of antibiotics and the consequent spread of resistance.

J Antimicrob Chemother, 1996 Nov, 38(5), 885 - 93
Antimicrobial practice . Development of guidelines for gentamicin dosing; Thomson AH et al.; The performance of dosage guidelines for starting gentamicin therapy was evaluated prospectively in 50 patients with suspected or proven Gram-negative septicaemia and the results were compared with results from similar group of 50 patients for whom the guidelines were not followed . Peak concentrations were significantly higher when the guidelines were followed (7.2 (+/- 1.9) mg/L vs 5.7 (+/- 1.8) mg/L) but there was no difference in trough concentrations . Fifty-eight per cent of patients had both peak and trough concentrations within the target range (peak > 5 mg/L, trough < 2 mg/L) when doses were decided empirically; this increased to 96% when the guidelines were followed . However, use of the guidelines achieved peaks of > 7 mg/L in only 56% of patients . A revised protocol with higher doses given less frequently was therefore developed and a prospective assessment of its performance indicated that satisfactory concentrations were obtained in 96% of patients.

Isr J Med Sci, 1996 Nov, 32(11), 1093 - 7
Surveillance of the use of antibiotic prophylaxis in surgery; Finkelstein R et al.; In 1991, updated recommendations for the administration of antimicrobial prophylaxis in surgery were made extensively available to all surgical wards of our hospital . Two years later we surveyed the implementation of these recommendations in our institution . Inpatients undergoing surgical procedures during a 6 month period were prospectively evaluated for the indication, type, timing and duration of antibiotic prophylaxis . On each day of the study, data of patients who underwent surgery in the previous 24-48 h were obtained and monitoring was continued for up to 5 days . Of the 215 evaluated patients 193 (90%) received prophylaxis . This rate was similar for elective and emergency surgeries . The rate of prophylaxis in surgeries for which its use is recommended was significantly higher than in surgeries where compelling data for its use are not available (96 vs . 74%, P = 0.000006) . However, many and important deviations of basic principles of antimicrobial prophylaxis in surgery were found . Prophylaxis was administered systematically in some types of surgery lacking compelling data for its use . In almost 50% of the surgical procedures the first dose of antimicrobial prophylaxis was not administered at the optimal timing; prophylaxis was continued for more than 24 h in 21% of the cases, and the use of unstandardized regimens was common . Despite the availability of local guidelines, the implementation of a hospital program with regard to antibiotic prophylaxis in surgery may be difficult . Further measures should be applied to achieve this goal.

J Vet Med Sci, 1996 Nov, 58(11), 1107 - 11
In vitro susceptibility of Mycoplasma hyosynoviae and M . hyorhinis to antimicrobial agents; Kobayashi H et al.; Fifty-four Japanese strains of Mycoplasma hyosynoviae isolated from porkers during 1980 to 1995, and 107 Japanese strains of M . hyorhinis isolated from piglets with respiratory disease during 1991 to 1994 were investigated for the in vitro activities of 13 antimicrobial agents {josamycin, tylosin, spiramycin, kitasamycin, erythromycin, lincomycin (LCM), kanamycin (KM), chloramphenicol (CP), thiamphenicol (TP), tiamulin (TML), oxytetracycline (OTC), chlortetracycline (CTC), and enrofloxacin (ERFX)} by the agar dilution method . Of the drugs tested TML showed the highest activity with minimum inhibitory concentration (MIC) of 0.013 to 0.1 microgram/ m/ (MIC90; 0.05 microgram/ml) against strains of M . hyosynoviae, and 0.2 to 0.78 microgram/ml (MIC90; 0.39 microgram/ml) against strains of M . hyorhinis . ERFX, LCM, most of the 16-membered macrolide antibiotics and tetracyclines also showed low MICs against both mycoplasma species . The susceptibility of KM, CP and TP to the mycoplasmas was considered to be of a secondary grade . Two of 54 strains of M . hyosynoviae, and 11 of 107 strains of M . hyorhinis showed resistance to all 14- and 16-membered macrolide antibiotics tested . Tetracyclines (OTC and CTC) showed a relatively broad MIC distribution from 0.1 to 6.25 micrograms/ml against the M . hyosynoviae strains tested . All of the strains isolated during 1980 to 1984 were susceptible at the concentration of 0.78 microgram/ml or less (MIC90; 0.78 microgram/ml) to OTC and 1.56 micrograms/ml or less (MIC90; 1.56 micrograms/ml) to CTC, while the susceptibility of strains isolated recently, during 1994 to 1995, was more than 0.78 microgram/ml (MIC90; 3.13 micrograms/ml) to OTC, and more than 1.56 micrograms/ml (MIC90; 6.25 micrograms/ml) to CTC.

J Gastroenterol, 1996 Nov, 31 Suppl 9, 44 - 7
Amoxicillin for the treatment of Helicobacter pylori infection; Hirschl AM et al.; Amoxicillin is one of the most active antimicrobials against Helicobacter pylori in vitro, with a minimum inhibitory concentration (MIC) of < or = 0.01-0.1 mg/l . Thus far, neither primary nor secondary resistant strains have been found . Amoxicillin, which has a bactericidal effect on H . pylori, but is less inhibitory in the stationary growth phase and against cell-adherent or slowly growing H . pylori, probably has both topical and systemic activity . It is fairly acid stable and is less affected by gastric acidity than macrolides . Nevertheless, its activity in vivo is considerably enhanced when it is given concomitantly with proton pump inhibitors . Several amoxicillin-containing treatment regimes have yielded H . pylori eradication rates of > or = 90% . Of particular interest are 1-week treatment regimens containing amoxicillin + clarithromycin + omeprazole, or amoxicillin + metronidazole + omeprazole, as well as a 1-h topical therapy developed in Japan.

Chemotherapy, 1996 Nov-Dec, 42(6), 459 - 64
Immunomodulatory action of levofloxacin on cytokine production by human peripheral blood mononuclear cells; Yoshimura T et al.; Levofloxacin (LVFX), the bacteriologically active isomer of ofloxacin, is a fluorinated quinolone . LVFX suppressed the proliferative activity of peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA) . LVFX increased interleukin-2 (IL-2) production by PBMC stimulated with PHA in a dose-dependent manner, with more than 10 micrograms/ml of LVFX causing a significant increase . The granulocyte-macrophage colony-stimulating factor and soluble IL-2 receptor production by PHA-stimulated PBMC was suppressed at high concentrations of LVFX . Interleukin-1 beta production by lipopolysaccharide-stimulated PBMC was suppressed in a concentration-dependent manner by LVFX, and tumor necrosis factor-alpha production was suppressed at only the highest concentration . In contrast, interleukin-8 production was little affected by LVFX . These results show that LVFX has an immunomodulatory action on cytokines production by PBMC independent of its antimicrobial activity.

Acta Paediatr, 1996 Nov, 85(11), 1290 - 4
Efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting; Bahl R et al.; OBJECTIVES: To determine the efficacy of antimicrobial treatment in non-dysenteric persistent diarrhoea in a community setting . METHODS: In this double-blind field trial, 156 children aged 4-36 months with persistent diarrhoea not associated with Giardia lamblia infestation seeking treatment in a community outpatient clinic, were randomized to receive a combination of nalidixic acid and metronidazole, metronidazole alone, or placebo for 7 days . RESULTS: In comparison with placebo, metronidazole treatment did not result in a significant reduction in the mean post-enrollment diarrhoeal duration and stool frequency, increase in the proportion of patients recovered by days 3, 5 and 7 of treatment, and increase in weight gain at days 7 and 14 . Comparing the combination of nalidixic acid and metronidazole with metronidazole alone, 17.5% more children treated with the combination recovered by day 3 of treatment (p = 0.08) and the mean stool frequency ascertained on day 7 for the previous 24 h was 26.8% less in them (p = 0.05) . The weight gains at days 7 and 14 were similar in the two groups . CONCLUSIONS: These findings indicate that metronidazole offers no therapeutic benefit in persistent diarrhoea not associated with Giardia lamblia and nalidixic acid has only a modest clinical benefit, which is not substantial enough to warrant its routine use.

J Oral Rehabil, 1996 Nov, 23(11), 729 - 32
The effects of adding chlorhexidine and polyhexamethylene bisguanide to a light-cured periodontal dressing material; Thorstensen AE et al.; The effect of adding two bisguanide antimicrobial agents (chlorhexidine and PHMB) on some physical properties of the light-cured periodontal dressing material Barricaid are reported . The physical properties tested were elastic modulus, initial and 10 min recovery strains, and tear stress . The addition of both chlorhexidine and PHMB solutions reduced the elastic modulus as did water . The addition of PHMB to Barricaid produced greater initial recovery in the strain test than either the addition of chlorhexidine or water, but there were no differences between the treatments after 10 min . Tear stress was also reduced by the addition of water and the chlorhexidine and PHMB solutions . These results suggest that as far as the physical properties of Barricaid are concerned the addition of the antimicrobial agent PHMB had no long-term advantages over chlorhexidine.

J Ethnopharmacol, 1996 Nov, 54(2-3), 143 - 51
Antimicrobial and immunological activity of ethanol extracts and fractions from Isopyrum thalictroides; Ivanovska N et al.; The antimicrobial and immunological properties of ethanol extracts, non-alkaloid, tertiary alkaloid and quaternary alkaloid fractions, obtained from roots and aerial parts of Isopyrum thalictroides were examined . The non-alkaloid fraction from aerial parts inhibited the growth of seven test microorganisms and was the most effective suppressor of classical pathway (CP) complement activity in normal human serum (NHS) and guinea pig serum (GPS) . The alkaloid fractions, containing quaternary alkaloids expressed suppressive effect on mitogen-induced splenocyte proliferation . The in vitro antibody response against sheep red blood cells (anti-SRBC) was inhibited by ethanol extracts and quaternary alkaloid fraction . The intraperitoneal (i.p.) application of ethanol extract and tertiary alkaloid fraction from aerial parts showed that they possess in vivo effect on alternative pathway (AP) complement activity, anti-SRBC response and delayed type hypersensitivity (DTH).

Nippon Rinsho, 1996 Nov, 54(11), 3125 - 9
{The effect of new quinolone antimicrobial agents and macrolide antibiotics on the clearance of theophylline}; Honma M; Many drugs have been found to increase or decrease the clearance of theophylline . Some of new quinolone antimicrobial agents (ciprofloxacin, enoxacin, pefloxacin and tosufloxacin) and macrolide antibiotics (erythromycin, troleandomycin, roxithromycin and clarithromycin), are potent inhibitors of the metabolism of theophylline . Concomitant administration of these drugs may, thus, prolong the half-life of theophylline, elevate serum theophylline concentrations, and increase the risk of theophylline-related adverse events . Therefore, these data indicate that careful clinical and pharmacokinetic monitoring of patients receiving both theophylline and some of antimicrobial agents should be carried out.

Pediatr Ann, 1996 Nov, 25(11), 620 - 9
The management of common infections in ambulatory children; Mason WH; Antimicrobial therapy of infection in ambulatory children remains the cornerstone of the pediatrician's practice . Despite a cornucopia of newer antimicrobial agents, the older "tried and true" drugs continue to be favored based on their history of effectiveness, lack of toxicity, and low price . It also is clear that the widespread use of antimicrobial agents has contributed to the development of resistance . We must reevaluate our antimicrobial use so that we only treat infections likely to benefit from antimicrobials . Better diagnostic techniques should be developed for rapid and accurate identification of pathogens . Finally, alternative therapeutic strategies should be investigated, such as shorter courses of treatment or use of vaccines, to lessen the selective pressure on the microbial flora . To fail to meet this challenge will mean the more rapid transition into the "postantibiotic era".

Vet Surg, 1996 Nov-Dec, 25(6), 487 - 94
Chlorhexidine gluconate versus chloroxylenol for preoperative skin preparation in dogs; Stubbs WP et al.; The efficacy of 3% chloroxylenol (PCMX) or 4% chlorhexidine gluconate (CG) for preoperative skin preparation was assessed in 100 dogs undergoing clean or clean-contaminated surgical procedures . Replication Organism Detection and Counting (RODAC) plates were used to quantify skin bacteria colony forming units (CFU) at the operative site before and after skin preparation and immediately postoperatively . Reduction of CFU after skin preparation and immediately postoperatively was significant for each agent . However, CFU levels were significantly lower in the CG group than in the PCMX group after surgical preparation, regardless of initial CFU numbers . No significant difference in CFU counts was observed between antiseptic groups postoperatively . Within-group comparisons showed PCMX to be significantly less efficacious when the prescrub CFU number was greater than 1,000 . Bacterial reduction was similar in the CG group regardless of prescrub CFU levels . The number of negative cultures after skin preparation was significantly greater with CG than with PCMX . Chlorhexidine gluconate also had fewer cultures with heavy bacterial growth (> 5 CFUs) after surgical preparation . There was no significant difference between antiseptics in the number of negative cultures or cultures with more than 5 CFUs immediately after surgery . The number of skin reactions and postoperative wound infections that occurred with each technique were similar . Three percent PCMX, as used in this study, was less effective than 4% CG in its immediate antimicrobial activity, however, this difference was not associated with an increased wound infection rate.

Clin Exp Immunol, 1996 Nov, 106(2), 367 - 73
Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens; Wang JY et al.; Human lung surfactant proteins A (SP-A) and D (SP-D) are both collagenous C-type lectins which appear to mediate antimicrobial activity by binding to carbohydrates on micro-organisms and to receptors on phagocytic cells . Purified native SP-A and SP-D, isolated from human bronchoalveolar lavage fluid, were found to bind to whole mite extracts (Dermatophagoides pteronyssinus) and the purified allergen Der p I, in a carbohydrate-specific and calcium-dependent manner . Binding was inhibited by ethylenediamine tetra-acetic acid (EDTA) as well as by maltose in the case of SP-D, or mannose in the case of SP-A . A recombinant polypeptide, which trimerized to form the neck region and carbohydrate recognition domains of SP-D, also inhibited the binding of native SP-D to the whole mite extract and Der p I . Both SP-A and SP-D did not bind to deglycosylated whole mite extracts or to recombinant Der p proteins, which lacked carbohydrate residues . These results suggest that the ability of surfactant proteins to bind certain allergens is mediated through their carbohydrate-recognition domains (CRDs) interacting with carbohydrate residues on the allergens . Moreover, SP-A and SP-D were found to inhibit allergen-specific IgE binding to the mite extracts either via steric hindrance or competitive binding . It is therefore possible that SP-A and SP-D may be involved in the modulation of allergen sensitization and/or the development of allergic reactions.

Int J Food Microbiol, 1996 Nov, 33(1), 51 - 64
Methods for preservation and extension of shelf life; Gould GW; There is potential for spoilage of all foods at some rate or other following harvest, slaughter or manufacture and spoilage may occur at any of the stages between the acquisition of raw materials and the eventual consumption of a food product . These stages include processing, packaging, distribution, retail display, transport, storage and use by the consumer . They are under varying degrees of control that aim to deliver a satisfactory shelf life, to ensure that the finally-consumed product is of high quality and to ensure that it is safe . Spoilage may be caused by a wide range of reactions including some that are essentially physical, some that are chemical, some enzymic and some microbiological . The various forms of microbiological spoilage are preventable to a large degree by a wide range of preservation techniques, most of which act by preventing or inhibiting microbial growth (e.g., chilling, freezing, drying, curing, conserving, vacuum packing, modified atmosphere packing, acidifying, fermenting and adding preservatives) . A smaller number of techniques act by inactivating microorganisms (e.g., pasteurization, sterilization and irradiation) . Additional techniques restrict the access of microorganisms to products (e.g., aseptic processing and packaging . A major trend is that new and emerging preservation techniques which are coming into use or are under development include more that act by inactivation (e.g., ultrahigh pressure, electroporation, manothermosonication and addition of bacteriolytic enzymes) . A further trend is towards the use of procedures that deliver products that are less heavily preserved, have higher quality, are more natural, freer from additives and nutritionally healthier . Less severe preservation procedures are therefore being developed that make use of preservative factors in combinations to deliver (a) less damage to product quality (hurdle technologies); (b) new methods of heating that are better controlled and therefore deliver milder heat to products; (c) cook-chill combinations that deliver longer high quality shelf lives: (d) modified atmosphere packaging to retain quality longer; and (e) use of antimicrobial systems that are more natural . Many of the existing and emerging preservation techniques act by interfering with the homeostatic mechanisms that microorganisms have evolved in order to survive extreme environmental stresses.

Ann Pharmacother, 1996 Nov, 30(11), 1291 - 7
Management of otitis media with effusion in young children; Paap CM; OBJECTIVE: To summarize and critique the Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline for the management of otitis media with effusion (OME) in children . DATA SOURCES: The AHCPR Clinical Practice Guideline, Otitis Media with Effusion in Young Children; the Quick Reference Guide for Clinicians, Managing Otitis Media with Effusion in Young Children; and the Parent Guide, Middle Ear Fluid in Young Children, were the primary data sources . The AHCPR developed the Guideline based on a comprehensive literature review from multiple bibliographic databases, including the National Library of Medicine . Data were also collected during open hearings and from unpublished sources derived from a call in the Federal Register . Additional citations from the biomedical literature were used for supporting evidence . STUDY SELECTION: Peer-reviewed reports of controlled, randomized studies were preferred, but other study designs were considered . Over 3000 abstracts were identified, of which 378 articles were used for data extraction, and an additional 100 articles were included from bibliography review and panel recommendations . An expert panel reviewed the data and incorporated clinical expertise into the development of consensus statements . DATA EXTRACTION: Data were extracted to apply to a base case with OME to narrow the scope of the Guideline . The base case was defined as a child who is 1-3 years old, is otherwise healthy, and has no underlying craniofacial, neurologic, or sensory conditions . Multiple meta-analyses were done to help the panel come to conclusions on several issues . DATA SYNTHESIS: The Guideline documents carefully outlined treatment algorithms for the management of OME in otherwise healthy children . The main areas that need to be further clarified are the role of more aggressive identification of causative pathogens, when antimicrobial therapy should be initiated, and which antimicrobial agents are preferred for the treatment of OME . There are many vague areas in the Guideline that allow for multiple interpretations . Data regarding the use of corticosteroids were influenced heavily by the expert opinion of the panel rather than the literature-based evidence and potential cost implications . The Guideline provided specific recommendations for the surgical management of OME . Confounding patient factors that would affect decisions on management of OME, such as underlying disease states and physical or mental abnormalities, were not addressed in the Guideline . CONCLUSIONS: The documents were well organized and provide detailed explanation of the recommendations . The Guideline provides specific criteria for the surgical management of OME, but is vague in its recommendations on the medical management of OME with antibiotics, corticosteroids, and the use of invasive tympanocentesis in the evaluation of OME in otherwise healthy children.

Mol Pharmacol, 1996 Nov, 50(5), 1095 - 102
Mechanisms of cell killing by drugs that trap covalent complexes between DNA topoisomerases and DNA; Nitiss JL et al.; DNA topoisomerases are the molecular targets of a range of anticancer and antimicrobial therapeutics . Many of these drugs act by converting their target enzyme to a DNA-damaging agent through the trapping of the covalent enzyme/DNA intermediate . This drug-mediated trapping of the intermediate is reversible, and the lesion in the DNA disappears on removal of the drug . This reversibility leads to questions concerning how treatment with these drugs effects cell killing . Using drug-permeable yeast strains, we demonstrate that yeast cells arrested in G1 are refractory to drugs that trap the covalent complex between DNA and either topoisomerase I or topoisomerase II . The cell cycle regulation of topoisomerase II is not responsible for the insensitivity of G1 cells to drugs targeting this enzyme because ectopic expression of the enzyme in G1 does not alter drug sensitivity . Commitment to cell killing by anti-topoisomerase II agents predominantly occurs in S phase cells but can also occur as cells progress from G2 through mitosis to G1 . We also demonstrate that yeast cells treated with DNA replication inhibitors such as aphidicolin lose sensitivity to camptothecin but not to topoisomerase II-targeting DNA-damaging agents . Our results suggest that DNA synthesis is a major determinant for cell killing by camptothecin but that other S phase-associated processes can effect cytotoxicity by drugs that convert topoisomerase II to a DNA-damaging agent.

Biopolymers, 1996 Nov, 39(5), 653 - 64
CD and NMR structural characterization of ceratotoxins, natural peptides with antimicrobial activity; Ragona L et al.; Antibacterial properties of the secretion from the female reproductive accessory glands of medfly Ceratitis capitata are mostly ascribed to the presence of two peptides, ceratotoxin A and B, which exhibit a strong activity against gram-positive and gram-negative bacterial strains, and show sequence and function homology with cecropins, melittin, and magainins . CD experiments performed in different solvents indicate the presence of a significant content of helical structures in organic solvent . Two-dimensional nmr results for ceratotoxin A in methanol show a helical behavior for the 8-25 region of the peptide . A ramachandran classification of each residue for the structures obtained from distance geometry calculations lead to the definition of four structural families in which the central segment 10-19 is always helical and differences refer to residues 8-9 and 19-23 . A sequence analysis of the two ceratotoxins and a systematic search on the protein data bank revealed the occurrence of a KX-hydrophobic-hydrophobic-P motif that seems to be important for helix stabilization.

Biochemistry, 1996 Oct 29, 35(43), 13723 - 8
Membrane pores induced by magainin; Ludtke SJ et al.; Magainin, found in the skin of Xenopus laevis, belongs to a broad class of antimicrobial peptides which kill bacteria by permeabilizing the cytoplasmic membrane but do not lyse eukaryotic cells . The 23-residue peptide has been shown to form an amphiphilic helix when associated with membranes . However, its molecular mechanism of action has been controversial . Oriented circular dichroism has detected helical magainin oriented perpendicular to the plane of the membrane at high peptide concentrations, but Raman, fluorescence, differential scanning calorimetry, and NMR all indicate that the peptide is associated with the head groups of the lipid bilayer . Here we show that neutron in-plane scattering detects pores formed by magainin 2 in membranes only when a substantial fraction of the peptide is oriented perpendicular to the membrane . The pores are almost twice as large as the alamethicin pores . On the basis of the in-plane scattering data, we propose a toroidal (or wormhole) model, which differs from the barrel-stave model of alamethicin in that the lipid bends back on itself like the inside of a torus . The bending requires a lateral expansion in the head group region of the bilayer . Magainin monomers play the role of fillers in the expansion region thereby stabilizing the pore . This molecular configuration is consistent with all published magainin data.

Transplantation, 1996 Oct 27, 62(8), 1185 - 7
Early onset of pulmonary mucormycosis with pulmonary vein thrombosis in a heart transplant recipient; Muhm M et al.; Pulmonary infections are major complications in heart transplantation . Progress in antimicrobial chemotherapy has switched the clinical spectrum to an increased incidence of fungal pathogens, such as Candida and Aspergillus species . Mucormycosis is a rare opportunistic infection with high mortality in solid-organ transplant recipients usually ensuing several months after transplantation . We describe a 45-year-old patient with pulmonary mucormycosis manifestion 5 days after heart transplantation . The infection resulted in pulmonary vein thrombosis followed by hemorrhagic infarction . Despite antifungal treatment and surgical resection, the patient died on day 14 after transplantation . Antemortem diagnostic procedures were negative; autopsy confirmed the presence of Rhizopus oryzae invading blood vessels . We conclude that physicians must be aware of mucormycosis even within one week after heart transplantation--which has not been described so far . Invasive diagnostic workup is mandatory in case of suspicion; amphotericin B and, in selected cases, surgical resection are the mainstays of therapy.

Ann N Y Acad Sci, 1996 Oct 25, 797, 228 - 39
Endogenous vertebrate antibiotics . Defensins, protegrins, and other cysteine-rich antimicrobial peptides; Lehrer RI et al.; Although newly recognized, endogenous cystine-stabilized beta-sheet antimicrobial peptides have ancient origins . These peptides can arm circulating phagocytes and cells of the gastrointestinal, respiratory, and genitourinary tracts to resist invasion by bacteria, mycobacteria, fungi, and enveloped viruses . Defensins and protegrin-like peptides are likely to play a considerable role in innate immunity and may provide molecular templates that can be used to generate novel antibiotics for topical and systemic use.

N Engl J Med, 1996 Oct 24, 335(17), 1270 - 4
Lyme disease in children in southeastern Connecticut . Pediatric Lyme Disease Study Group; Gerber MA et al.; BACKGROUND: Although the incidence of Lyme disease is highest in children, there are few prospective data on the clinical manifestations and outcomes in children . METHODS: We conducted a prospective, longitudinal, community-based cohort study of children with newly diagnosed Lyme disease in an area of Connecticut in which the disease is highly endemic . We obtained clinical and demographic information and performed serial antibody tests and follow-up evaluations . RESULTS: Over a period of 20 months, 201 consecutive patients were enrolled; their median age was 7 years (range, 1 to 21) . The initial clinical manifestations of Lyme disease were a single erythema migrans lesion in 66 percent, multiple erythema migrans lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent, aseptic meningitis in 2 percent, and carditis in 0.5 percent . At presentation, 37 percent of the patients with a single erythema migrans lesion and 89 percent of those with multiple erythema migrans lesions had antibodies against Borrelia burgdorferi . All but 3 of the 201 patients were treated for two to four weeks with conventional antimicrobial therapy, which was administered orally in 96 percent . All had prompt clinical responses . After four weeks, 94 percent were completely asymptomatic (including the two patients whose parents had refused to allow antimicrobial treatment) . At follow-up a mean of 25.4 months later, none of the patients had evidence of either chronic or recurrent Lyme disease . Six patients subsequently had a new episode of erythema migrans . CONCLUSIONS: About 90 percent of children with Lyme disease present with erythema migrans, which is an early stage of the disease . The prognosis is excellent for those with early Lyme disease who are treated promptly with conventional courses of antimicrobial agents.

EMBO J, 1996 Oct 15, 15(20), 5668 - 78
Inhibition of E2F-mediated transcription by p202; Choubey D et al.; Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins . Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb) . Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes . Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F . p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo . Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons.

FEBS Lett, 1996 Oct 14, 395(1), 48 - 52
Requirements for antibacterial and hemolytic activities in the bovine neutrophil derived 13-residue peptide indolicidin; Subbalakshmi C et al.; The antimicrobial and hemolytic activities of the 13-residue peptide indolicidin (ILPWKWPWWPWRR-NH2), present in bovine neutrophils, and its analogs have been determined with a view to gaining insight into the structural roles of tryptophan and proline . Peptides where proline was replaced by alanine and tryptophan by phenylalanine showed antibacterial activities comparable to that of indolicidin . The peptides do not exhibit a strong propensity to occur in either helical or beta-sheet conformation . The peptides also do not appear to exert their activity by permeabilizing the bacterial plasma membrane unlike other endogenous antibacterial peptides . The presence of tryptophan appears to be essential for hemolytic activity as the phenylalanine analog does not exhibit any hemolytic activity.

Caring, 1996 Nov, 15(11), 34 - 7, 41
Antimicrobial acetate fibers: a step forward in health care textiles; Gruender M; Health care providers are constantly battling the microorganisms that cause disease and infection . New textile products give professionals another weapon against these microscopic enemies.

Mol Divers, 1996 Oct, 2(1-2), 41 - 5
Libraries from libraries: generation and comparison of screening profiles; Houghten RA et al.; A positional scanning tetrapeptide library was chemically modified through alkylation and/or reduction of the amide bonds, thus generating three new combinatorial libraries with physico-chemical properties very different from the parent peptide library ('libraries from libraries') . Specific results were obtained with each of these libraries upon screening in kappa-opioid receptor binding and microdilution antimicrobial assays, illustrating the potential of the 'libraries from libraries' concept for the efficient generation of a variety of chemically diverse combinatorial libraries.

J Pharmacokinet Biopharm, 1996 Oct, 24(5), 509 - 19
N-acetyltransferases: pharmacogenetics and clinical consequences of polymorphic drug metabolism; Spielberg SP; Since the discovery of polymorphic N-acetylation of drugs nearly 40 years ago, great progress has been made in understanding the molecular genetics of acetylation as well as the clinical consequences of being a rapid or slow acetylator . Inborn errors (several different alleles) at the NAT2 locus are responsible for the traditional acetylator polymorphism . Studies have revealed variant alleles at the NAT1 locus as well . The consequences of pharmacogenetic variation in these enzymes include (i) altered kinetics of specific drug substrates; (ii) drug-drug interactions resulting from altered kinetics; (iii) idiosyncratic adverse drug reactions . The latter have been extensively investigated for the arylamine-containing sulfonamide antimicrobial drugs . Individual differences in multiple metabolic pathways can increase the likelihood of covalent binding of reactive metabolites of the drugs to cell macromolecules with resultant cytotoxicity and immune response to neoantigens . This can result clinically in an idiosyncratic hypersensitivity reaction, manifested by fever, skin rash, and variable toxicity to organs including liver, bone marrow, kidney, lung, heart, and thyroid . Slow acetylation by NAT2 is a risk factor for such reactions to sulfonamides . Given the incidence of these severe adverse drug reactions (much less than 1/1000), slow acetylation cannot be the sole mechanism of predisposition in the population . Differences in rates of production of hydroxylamine metabolites of the drugs by cytochrome P450 (CYP2C9), myeloperoxidase, and thyroid, roxidase, along with an inherited abnormality in detoxification of the hydroxylamines are critically important in determining individual differences in adverse reaction risk . Both NATs, particularly NAT1, also can further metabolize hydroxylamine metabolites to N-acetoxy derivatives . Intensive investigation of patients with these rare adverse reactions using a variety of tools from in vitro cell toxicity assays through molecular genetic analysis will help elucidate mechanisms of predisposition and ultimately lead to diagnostic tools to characterize individual risk and prevent idiosyncratic drug toxicity.

Ital J Gastroenterol, 1996 Oct-Nov, 28(8), 430 - 5
Helicobacter pylori gastritis and non-ulcer dyspepsia in childhood . Efficacy of one-week triple antimicrobial therapy in eradicating the organism; Cucchiara S et al.; Efficacy of one-week triple antimicrobial therapy (bismuth, tinidazole, amoxicillin) as compared to the same drug combination given for 4 weeks was assessed in children with Helicobacter pylori (H . pylori) gastritis and non-ulcer dyspepsia . Twenty-six patients (group A) and 30 (group B) had one-week and four-week schedule, respectively . Eradication (absence of organism at endoscopy at least 1 month after ending treatment) was achieved in 84.6% of group A (22) and 83.3% of group B (25), with marked reduction of histological gastritis score in both groups . Among patients with eradicated H . pylori, symptoms improved significantly in 14 and 16 patients of group A and B, respectively, but were still present in 17 (8 group A, 9 group B) . The latter showed gastroparesis and abnormal gastro-oesophageal reflux at a subsequent diagnostic work-up and improved with prokinetic therapy . In 3 patients of group A and 3 of group B, symptoms improved despite persistence of bacterium into the stomach . Finally, in 3 cases (1 group A, 2 group B) both symptoms and H . pylori infection were unchanged . At 6 month follow-up, symptoms were present in 7 patients (3 group A, 4 group B): 6 of them (3 group A, 3 group B) showed H . pylori gastritis at endoscopy . We conclude that in children with dyspepsia and H . pylori gastritis one-week triple antimicrobial schedule is effective in eradicating bacterium; however, detection of H . pylori gastritis in dyspeptic children does not invariably indicate a pathogenic role of the organism in these patients.

Lett Appl Microbiol, 1996 Oct, 23(4), 205 - 7
Antimicrobial effects of hydrophilic extracts of Pelargonium species (Geraniaceae); Lis-Balchin M et al.; Methanolic extracts of representative species and cultivars of Pelargonium (Geraniaceae) were assessed for activity against 25 different species of bacteria and Aspergillus niger . All samples were active against at least 18 bacterial species and some were active against all 25 species, although there was very poor antifungal action . Antioxidant action was very pronounced, and this together with the strong antibacterial activity indicates that there is a potential usage in the food or other industry for Pelargonium extracts.

Diagn Microbiol Infect Dis, 1996 Oct, 26(2), 99 - 102
Medium and supplement effects on the antimicrobial activity of quinupristin/dalfopristin tested by agar dilution and Etest methods; Jones RN; Quinupristin/dalfopristin (also known as RP-59500 and Synercid), a streptogramin combination has been documented as active against a wide variety of Gram-positive species . Broad ranges of MIC results have been observed with some species using acceptable susceptibility testing methods . To address the contribution of testing medium and supplements to this disagreement, 15 medium or supplement alterations were studied in a reference agar dilution format and three variations of Mueller-Hinton agar were used for Etest (AB Biodisk, Solna, Sweden) . One-third of the agar dilution variations produced a consistent elevation (twofold) in the quinupristin/dalfopristin MIC . The greatest changes were secondary to additions of serum and blood, pH increases, and possibly charcoal . Similarly, the Etest MICs for quinupristin/dalfopristin were 0.5 to 2.5 log2 dilutions higher with media supplemented with 5% sheep erythrocytes or when chocolated . Additional quinupristin/dalfopristin stability experiments in three agars indicate a two- to fourfold decline in potency over 21 days of storage at 2 to 5 degrees C . These variations in the streptogramin MIC results would be observed most frequently when testing fastidious species or in laboratories routinely testing all Gram-positive bacteria in or on blood-supplemented media.

J Nat Prod, 1996 Oct, 59(10), 985 - 6
Isolation of guaianoid pigments from the gorgonian Calicogorgia granulosa; Seo Y et al.; Three pigments of the guaiazulene class have been isolated from the gorgonian Calicogorgia granulosa . Structures of these compounds have been determined as guaiazulene, 2,2'- diguaiazulenylmethane, and a new compound, 2,2'-biguaiazulenyl, by combined chemical and spectroscopic methods . 2,2'-Biguaiazulenyl exhibited moderate antimicrobial activity.

Farmaco, 1996 Oct, 51(10), 659 - 64
3,6-Disubstituted 1,2,4-triazolo{3,4-b}{1,3,4}thiadiazoles: synthesis, antimicrobial and antiviral activity . II; Invidiata FP et al.; A series of novel 3,6-disubstituted 1,2,4-triazolo{3,4-b}{1,3,4} thiadiazole derivatives was prepared and tested to evaluate their antimycotic and antibacterial activities . Anti-HIV-1 activity has also been investigated . Among the test compounds, derivatives 10a-14a and 16c showed anti-HIV-1 activity at concentrations slightly below those cytotoxic . Substitutions at 3 and 6 positions seems to be important in lowering the cytotoxicity of compounds.

Schweiz Rundsch Med Prax, 1996 Oct 1, 85(40), 1253 - 4
{Tips and requests by microbiologists}; Wust J; Useful results of microbiological examinations can only be expected, when the specimens submitted to the laboratory are taken correctly . This overview shows appropriate and inappropriate specimens . Hints are given for a 'calculated antimicrobial chemotherapy' . A brief outline shows which bacteria should be tested for susceptibility to antimicrobial agents due to variable sensitivity.

J Chemother, 1996 Oct, 8(5), 382 - 6
Imipenem/cilastatin monotherapy as salvage treatment in febrile neutropenic patients; Engervall P et al.; Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy . Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone . Twenty-five out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47%) as failures . In episodes with documented infections 9 out of 23 (39%) were classified as success . All patients survived during the first 72 hours after change to I/C therapy . One patient had to discontinue I/C due to a skin rash . In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective . Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.

J Chemother, 1996 Oct, 8(5), 342 - 50
Antimicrobial agents rationale and monitoring in an Italian hospital; De Lalla F; Optimizing the use of antimicrobial agents may impact considerably on the total pharmaceutical costs sustained by any given hospital . At the San Bortolo Hospital in Vicenza, Italy, antimicrobial usage was monitored over an 18-month period and a cost analysis was performed . In 1993 the cost for antimicrobial agents was 20.3% of the total pharmaceutical costs of the hospital budget . Third-generation cephalosporins were the most frequently used class of drugs . In order to rationalize costs, actions put into place in the first few months of 1993 included, among others, an update of the hospital formulary and adoption of a request procedure for obtaining antimicrobial agents outside the formulary . There was a trend towards a reduction in the cost of antimicrobial therapy (6 to 7% savings for the acquisition of antimicrobial agents) in the first semester of 1994 compared with the same time period in 1993 . This cost reduction was accomplished mainly by an increase in the use of some less expensive agents, in particular first- and second-generation cephalosporins, but also by a decrease in the use of teicoplanin, imipenem-cilastatin, ceftazidime and ureidopenicillins.

J Chemother, 1996 Oct, 8(5), 331 - 41
Antimicrobial treatment of periodontal diseases disturbs the human ecology: a review; Edlund C et al.; Periodontal diseases are associated with specific pathogenic microorganisms and therefore antimicrobial agents are often used in the treatment of patients with periodontitis refractory to conventional mechanical therapy . Perorally administered antimicrobial agents often lead to ecological disturbances in the normal oral and intestinal microflora with overgrowth of potentially pathogenic microorganisms, which may spread within the host or from patient to patient, causing infections . The use of antimicrobial agents also promotes the emergence of bacterial drug resistance, both in the periodontal pocket and in the normal oral and intestinal microflora . Topical administration of antimicrobial agents in the periodontal pockets causes restricted disturbances in the intestinal microflora, although there is a substantial risk of development of resistance at the site of application . A number of clinical studies imply that correct use of antimicrobial agents might be beneficial for a subset of patients with adult or juvenile periodontitis . The choice of antimicrobial agent should always be based on accurate microbial analyses of the subgingival microflora and in vitro antimicrobial susceptibility tests of the most important periodontal pathogens . Preferably, agents with low potential of causing ecological disturbances should be used.

Eur J Cancer, 1996 Oct, 32A(11), 1938 - 42
High-dose melphalan followed by autograft employing non-cryopreserved peripheral blood progenitor cells in children; Jones N et al.; High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) enables dose escalation in the treatment of childhood malignancies . Here we report our experience of using peripheral blood progenitor cells (PBPC) to restore haematopoiesis in five children using a simple cell mobilising regime and non-cryopreservation of the harvests . Cells were mobilised using cyclophosphamide and granulocyte colony stimulating factor . Each patient underwent only two leukaphereses, the product being stored before use at 4 degrees C . Successful autologous PBPC transplantation was achieved with melphalan conditioning chemotherapy and re-infusion of the total progenitor cell product . No colony stimulating factors were administered after transplantation . The median numbers of mononuclear cells collected per patient was 10.0 x 10(8)/kg (range 8.13-19.44) and CFU-GM 57.6 x 10(4)/kg (range 10.4-178.85) . All patients subsequently engrafted with the median number of days to a neutrophil count > 0.5 x 10(9)/l being 11 (range 10-16), and to a platelet count > 50 x 10(9)/l being 14 (range 12-31) . The median number of in-patient days was only 20 (range 19-30) . The median demand for blood was 2 units (range 1-2), and platelets 4 units (range 2-28) . Usage of systemic antimicrobials and intravenous feeding was also low . Using this simple strategy, collection and transplantation of autologous progenitor cells can be a straightforward procedure in children . It is possible that this could enable dose escalation in some poor prognosis paediatric tumours.

Pharmazie, 1996 Oct, 51(10), 727 - 31
QSAR and CAMM study of amphiphilic antimicrobially active 2,2'-bipyridyl monoammonium salts; Devinsky F et al.; Preparation of 2,2'-bipyridyl monoammonium salts is described as well as their conformation study using computer aided molecular modelling (CAMM) methods and quantitative relations between structure, aggregation properties and antimicrobial activity (QSAR) of these derivatives . It was found that using the applied synthetic route the monoammonium salt is prepared free of bis-ammonium salt . While in the case of the unsubstituted 2,2'-bipyridyl the energy difference between s-cis and s-trans conformers is minor and the transition from one state into the other one is possible with s-trans state apparently being preferred, after quaternisation the exclusive conformer is s-cis that is in this state fixed except of steric hindrance between the alkyl substituent bonded to the N+ atom and the hydrogen bonded to 3'C also by a weak hydrogen interaction C-H .. . N between the hydrogen of the first carbon of the alkyl chain and the nitrogen of the adjacent ring . This finding is supported also by the results of calculation of point electric charges, dipole moments, 2C-2'C distance and torsion angles of non-quaternised as well as bipyridinium cations . It follows from quantitative dependencies between lipophilicity (expressed by means of aggregation properties-by critical concentration of micelle formation ck, and chromatographic factor RM), structure (length of alkyl chain m) and antimicrobial activity (minimum inhibition concentration, MIC) that the maximum of activity is achieved with compounds of chain length m = 13 to 16 with ck about 1.10(-3) mol/l . It follows from the comparison with simple alkylpyridinium salts that the mechanism of biological activity at the bacterial level will not differ in 2,2'-dipyridyl derivatives from the mechanism of activity of other ammonium salts.

Aust Vet J, 1996 Oct, 74(4), 277 - 80
Owner compliance with short term antimicrobial medication in dogs; Barter LS et al.; The degree to which dog owners complied with instructions to administer a 5 to 10 day course of antimicrobial medication to their pets was assessed using microprocessor based monitoring devices . Twenty two clients gave an average of 84% of prescribed doses of amoxycillin-clavulanate . No difference was found between twice and thrice daily dosing regimens in the overall percentage of prescribed doses given . However, timing of doses was far from ideal in many cases and only 34% of doses were given within the designated optimum time period . Adherence to desired dosing intervals tended to be better with twice daily than with thrice daily dosing, although the difference was statistically insignificant.

Eur J Gastroenterol Hepatol, 1996 Oct, 8 Suppl 1, S3 - 7
The changing role of H2-receptor antagonists in acid-related diseases; Lamers CB; BACKGROUND: H2-receptor antagonists have been the mainstay of treatment for acid-peptic disease for many years . These compounds have proved to be more effective than antacids and without relevant side effects . However, their primacy has recently been challenged . First, the discovery of Helicobacter pylori and its effects on peptic ulcer disease has indicated the need for antimicrobial therapy . Second, the development of proton-pump inhibitors with potent and long-lasting antisecretory effects has largely changed the approach to acid inhibition therapy . DIFFERENCES BETWEEN H2-RECEPTOR ANTAGONISTS AND PROTON-PUMP INHIBITORS: There are important differences in the mechanism of action whereby H2-receptor antagonists and proton-pump inhibitors reduce gastric acid secretion . These differences lead to differences in the degree and duration of acid inhibition: repeated doses of proton-pump inhibitors are needed in order to reach the maximum antisecretory effect, whereas the acid-inhibitory effect of H2-receptor antagonists is achieved within hours, although it tends to fade during prolonged treatment . CONCLUSIONS: For erosive and ulcerative reflux esophagitis, H2-receptor antagonists have been largely replaced by proton-pump inhibitors, while for peptic ulcer disease, therapy for H.pylori eradication is now recommended . In the future, H2-receptor antagonists may be used mainly for mild to moderate gastroesophageal reflux disease and these drugs may be available as over-the-counter medication in several countries.

Intensive Care Med, 1996 Oct, 22 Suppl 4, S456 - 61
Current and future clinical applications of interferon-gamma in host antimicrobial defense; Murray HW; The T cell-derived macrophage-activating lymphokine, interferon-gamma (IFN-gamma), is the most broadly acting antimicrobial-inducing and host defense-enhancing cytokine thus far identified in experimental models of infectious diseases . The activity induced by IFN-gamma encompasses all classes of non-viral pathogens including intracellular and extracellular parasites, fungi and bacteria . In man, treatment with immuno-enhancing doses of IFN-gamma is safe, well-tolerated and stimulates the antimicrobial mechanisms of blood monocytes, circulating neutrophils and tissue macrophages . Aerosol administration activates alveolar macrophages in a compartmentalized fashion . Monocytes from IFN-gamma-treated patients with cancer, leprosy, and AIDS all respond with the activated phenotype, and suppressed monocyte HLA-DR expression in trauma patients can be up-regulated by IFN-gamma therapy . Thus far, IFN-gamma has been recognized as effective in the prophylaxis of chronic granulomatous disease and as adjunctive treatment in at least one systemic intracellular infection, visceral leishmaniasis . Additional trials suggest beneficial effects as prophylaxis in trauma and as treatment in leprosy, cutaneous leishmaniasis, and HIV- and non-HIV-related disseminated atypical mycobacterial infection . IFN-gamma is also being tested as a prophylaxis in patients with burns and advanced HIV infection and as an adjunct in drug-resistant tuberculosis . Future antimicrobial applications for IFN-gamma include: a) long-term prophylaxis in T cell-deficient states, b) short-term prophylaxis in patients with a reversible host defense defect such as granulocytopenia or immune response suppression induced by trauma or burn injury, and c) adjunctive treatment along with conventional antibiotic therapy for i) nosocomial pneumonia (aerosol administration), ii) opportunistic infections in general, iii) infections which typically respond poorly to available treatment and iv) for infections which require prolonged therapy for cure . In the latter, the addition of IFN-gamma may accelerate the response to conventional therapy and permit a clinically important reduction in the duration of treatment while preserving efficacy.

Intensive Care Med, 1996 Oct, 22(10), 1098 - 104
Complications of care in a pediatric intensive care unit: a prospective study; Stambouly JJ et al.; OBJECTIVES: (a) To examine the frequency, type, and severity of complications occurring in a pediatric intensive care unit; (b) to identify populations at risk; and (c) to study the impact of complications on morbidity and mortality . DESIGN: Prospective survey . SETTING: Pediatric intensive care unit (PICU) of a university-affiliated hospital . PATIENTS: 1035 consecutive admissions over an 18-month period . RESULTS: 115 complications occurred during 83 (8.0%) admissions, for 2.7 complications per 100 PICU-days; 48 (42%) complications were major, 45 (39%) moderate, and 22 (19%) minor . Sixty complications (52%) were ventilator-related, 14 were drug-related, 13 procedure-related, 24 infectious, and 22 involved invasive devices (18 vascular catheters) . Human error was involved in 41 (36%) cases, 21 of which were major (18%) . Treatments included reintubation < 24 h (28), intravenous antimicrobials (24), and invasive bedside procedures (14) . Cardiopulmonary resuscitation was required in 6 patients . Thirteen patients with complications died (15.7%); 2 deaths were directly due to complications . Patients with complications were younger, had longer lengths of stay, and had a higher mortality . Length of stay was a positive risk factor for complication risk (odds ratio = 1.09, 95% confidence interval: 1.05 to 1.13; p = 0.0001); other patient characteristics had no predictive effect . Kaplan-Meier estimates showed that the most severe complications occurred early in the PICU stay . The best indicators of patient mortality were number of complications (odds ratio = 2.96, 95% confidence interval 1.72 to 5.08; p = 0.0001), and mortality risk derived from the Pediatric Risk of Mortality Score (odds ratio = 1.08, 95% confidence interval 1.06 to 1.10; p = 0.0001) . Mortality was correlated with increasing severity of complications . CONCLUSION: Complications have a significant impact on patient care . Patients may be at increased risk earlier in their PICU course, when the number of interventions may be greatest . Complications may increase patient mortality and predict patient death better than other patient variables.

J Clin Periodontol, 1996 Oct, 23(10), 898 - 905
Supportive care after active periodontal treatment: a review; Echeverria JJ et al.; This review concerns the most significant questions regarding supportive (maintenance) care after active periodontal treatment: the effectiveness and ideal frequency of maintenance appointments, the adequacy of the supportive therapy according to patient needs, the possible alternatives to currently accepted protocols, and the relative value of personal oral hygiene in the overall context of supportive care . Periodontal diseases are infections with a high potential for recurrence, progressive loss of attachment and eventually, tooth loss . Current therapies for periodontal diseases are highly predictable in arresting disease activity . Supportive periodontal care has been shown to be very effective in maintaining support when adapted to each particular case . Nevertheless, current maintenance therapies may be unsuccessful in preventing further loss of attachment in a small number of sites for some patients . Tests aiming at bacterial identification and the subgingival application of antimicrobials may be helpful in the management of such cases, however the practical value in a specific setting is not known . There is growing evidence of the fundamental role of personal oral hygiene in supportive periodontal care . In cases with rapid and severe periodontal destruction and where local and/or systemic risk factors are present, personal oral hygiene becomes a key factor in the long-term preservation of periodontal support.

Kyobu Geka, 1996 Oct, 49(11), 939 - 42
{Subacute effusive-constrictive pericarditis accompanied with miliary tuberculosis: a case report}; Watanabe S et al.; With the advent and the introduction of effective antimicrobial therapy, the mortality for tuberculosis pericarditis decreased in number dramatically . The problems, however, remains in several severe cases . We have experienced a rare case of 74 year old male with subacute effusive-constrictive pericarditis accompanied with miliary tuberculosis . The patient revealed improvement immediately after early an emergent pericardiectomy . However cardiac failure recurred thereafter because of fibrous epicarditis of tuberculous inflammation . Management of subacute effusive-constrictive pericarditis as this has many problems including surgical intervention such as operative timing and indication and/or role of corticosteroids together with antituberculotic drugs.

Steroids, 1996 Oct, 61(10), 565 - 71
The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6 beta-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid; Jones SR et al.; Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid . After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization . Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3 alpha and 3 beta addition products . The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound . Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents . The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.

J Periodontol, 1996 Oct, 67(10 Suppl), 1094 - 102
Response to periodontal therapy in diabetics and smokers; Grossi SG et al.; Diabetics and smokers are two patient groups at high risk for periodontal disease who also exhibit impaired wound healing and, therefore, constitute two different groups in whom the relationship between host-parasite interaction, outcome of periodontal therapy, and systemic factors is best represented . The results of two independent clinical trials involving treatment of periodontal disease in diabetics and smokers are presented . A new treatment regimen for the management of periodontal disease associated with diabetes mellitus is proposed . This treatment approach incorporates both antimicrobial agents and pharmacological modulation of the host response . Elimination of periodontal infection and reduction of periodontal inflammation in diabetic patients resulted in a significant short-term reduction in the concentration of glycosylated hemoglobin (HbA1c) . Control of chronic infections and modulation of the host response offer a new therapeutic approach in the management of patients with both diabetes and periodontal disease . The effect of smoking on periodontal healing is also discussed . The clinical and microbiological response of smokers to non-surgical periodontal therapy is compared to non-smokers . In addition, possible mechanisms whereby diabetes mellitus and cigarette smoking increase the severity of periodontal disease are discussed.

Clin Infect Dis, 1996 Oct, 23(4), 790 - 4
Crisis in infectious diseases: time for a new paradigm?
Casadevall A.
Current practices in the treatment of infectious diseases are the result of two fundamental changes in antimicrobial therapy that occurred in the mid-20th century: the transition from pathogen-specific therapy to non-pathogen-specific therapy and the shift toward emphasis on antiinfective strategies that target microbial pathogens over those that enhance host immunity . The alarming rise in antimicrobial-resistant strains, the increasing frequency of serious infections in immunocompromised patients, and the paucity of new types of antibiotics suggest the need for reevaluation of the manner in which infections are treated . In the short term, the situation may be addressed-at least in part-by increased emphasis on improved diagnosis and, when possible, the use of specific or narrow-spectrum treatments . In the long term, a return to pathogen-specific therapy, possibly in combination with adjunctive immunotherapy, may be an attractive and desirable option provided that significant advances are made in diagnostic microbiology and drug discovery.

Xenobiotica, 1996 Oct, 26(10), 1057 - 66
Intermolecular interactions of antimicrobial fluoroquinolones with purified rat liver CYP1A2 studied by proton nuclear magnetic resonance spectroscopy; Mizuki Y et al.; 1 . Binding and inhibition of antimicrobial fluoroquinolones towards liver CYP1A2 purified from 3-methylcholanthrene-treated rats were investigated using proton nuclear magnetic resonance (nmr) and phenacetin metabolism . 2 . The proton nmr longitudinal relaxation rate study indicated that the paramagnetic effects of the haem iron of CYP1A2 were observed in protons of enoxacin with a 1,8-naphthyridine skeleton and its 4'-nitrogen atom on the 7-piperazine ring probably participated in specific binding to the haem iron . These data suggest a facile accessibility and strong binding of enoxacin to the active site of the enzyme . On the contrary, the binding region of norfloxacin with a quinoline skeleton could not be specified, and an 8-fluorinated derivative (AT-3970) had much lower paramagnetic effects and no specific binding region . 3 . In a reconstituted CYP1A2 system, enoxacin exhibited the most potent inhibition of phenacetin O-deethylation . The metabolism was less inhibited by norfloxacin, and AT-3970 had a weak inhibitory activity . 4 . The binding ability of the fluoroquinolones to the CYP1A2 active site is likely to determine their inhibitory activity against phenacetin metabolism.

J Vet Pharmacol Ther, 1996 Oct, 19(5), 397 - 401
In vitro susceptibility of Escherichia coli strains isolated from diarrhoeic lambs and goat kids to 14 antimicrobial agents; Cid D et al.; The in vitro activities of 14 anti-microbial agents were determined against 92 strains of E . coli isolated from lambs (60 strains) and kids (32 strains) affected by neonatal diarrhoea . The overall percentage of resistant strains to streptomycin, sulphadimethoxine and tetracycline was very high (above 70%) . A high level of resistance (from 30% to 50%) to ampicillin, kanamycin, neomycin and chloramphenicol was also detected . The E . coli strains were highly susceptible to cephalosporins, polymyxin and quinolones . Most of the strains showed multiresistance: 77.2% of isolates were resistant to at least two antibiotics, 55.4% were resistant to at least four antibiotics and 33.7% were resistant to at least six antibiotics . A total of 34 antibiotypes could be distinguished.

J Nat Prod, 1996 Oct, 59(10), 927 - 34
Isolation and structure of hemibastadinols 1-3 from the Papua New Guinea marine sponge Ianthella basta; Pettit GR et al.; Further investigation of the Bismarck Archipelago (Papua New Guinea) marine sponge Ianthella basta for biologically active constituents has led to the isolation of hemibastadins 1 (2), 2 (3), and 3 (4) and the new brominated tyrosine derivatives hemibastadinols 1-3 (9, 13, and 14) . Isolation and structure elucidation of the monomethyl ether derivatives (7 and 8) of hemibastadins 1 and 2 and the 3-bromotyramine amide of oxalic acid amide (1a) concluded our chemical investigation of I . basta . The hemibastadins and hemibastadinols represent important biosynthetic links to a series of bromotyrosine tetramers collectively known as the bastadins . The antimicrobial activity of the bastadins, hemibastadins, and hemibastadinols is summarized.

Chem Pharm Bull (Tokyo), 1996 Oct, 44(10), 1890 - 8
Development of bioactive functions in Hydrangeae dulcis folium . VI . Syntheses of thunberginols A and F and their 3'-deoxy-derivatives using regiospecific lactonization of stilbene carboxylic acid: structures and inhibitory activity on histamine release of hydramacrophyllols A and B; Yoshikawa M et al.; Lactonization reaction of 2-carboxystilbene mediated by copper(II) chloride proceeded regiospecifically to give the five-membered lactone, while the bromolactonizations using N-bromosuccinimide and anodic oxidation were found to furnish the six-membered lactone . Using these regiospecific lactonization reactions as a key step, antiallergic and antimicrobial isocoumarins and the benzylidenephthalides thunberginols A and F and their 3'-deoxyanalogs were synthesized from phyllodulcin and hydrangenol . Two phthalides called hydramacrophyllols A and B were isolated from Hydrangeae Dulcis Folium and their stereostructures were determined on the basis of physicochemical and chemical evidence, which included the syntheses of hydramacrophyllols A and B from hydrangenol by the application of the lactonization method using copper(II) chloride . In addition, hydramacrophyllols A and B were found to exhibit an inhibitory effect on the histamine release from rat peritoneal exudate cells induced by antigen-antibody reaction.

Clin Podiatr Med Surg, 1996 Oct, 13(4), 671 - 82
Management of diabetic foot infections, including the use of home intravenous antibiotic therapy; Fox HR et al.; Osteomyelitis and soft-tissue foot infections continue to be the source of major amputations in the diabetic patient . Many of these amputations can be prevented with a prompt, aggressive, and integrated approach . Foot alterations should be appropriately investigated for osteomyelitis and culture-driven antimicrobial therapy combined with aggressive surgical intervention, including revascularization when necessary, should be pursued . This approach increases the chances for limb salvage . Early discharge from the hospital with HIVAT offers a safe and effective alternative to a prolonged hospital stay with significant cost savings in appropriately selected patients.

Infect Control Hosp Epidemiol, 1996 Oct, 17(10), 668 - 9
Antimicrobial use in patients with positive intravascular catheter cultures: a six-month prospective survey in a teaching hospital; Rello J et al.; Review of medical records revealed that, of 190 intravascular catheters sent for culture during the study period, 50 were positive . Of these 50, 11 (22%) were sent for culture as a routine procedure without special clinical indications . Of the remaining 39 cultures, only 11 (28%) had clinical impact in the patient's management . Ten of the 50 therapeutic interventions were inappropriate . Restricting cultures to patients who may have catheter-related infection is likely to lead to significant cost savings.

Cryobiology, 1996 Oct, 33(5), 581 - 8
Effects of cryopreservation on immune responses . X . Decrease in interleukin-12 production by frozen human peripheral blood mononuclear cells is mediated by the endogenously hypersecreted interleukin-10; Venkataraman M; The contrasting effects of freezing and radiation on lipopolysaccharide (LPS)-induced interleukin (IL)-10 production by human peripheral blood mononuclear cells (PBMCs) have recently been reported . In view of the potent inhibitory properties of IL-10 on IL-12 secretion and the central role played by IL-12 in the immune system, the influences of freezing and radiation on LPS-induced IL-12 production by PBMCs were studied . Frozen PBMCs secreted significantly smaller amounts of IL-12 than fresh cells . In contrast, the in vitro-irradiated PBMCs produced significantly larger amounts of IL-12 . Culture of frozen cells in the presence of exogenous anti-IL-10 antibody resulted in the production of significantly larger amounts of IL-12 . These results suggest that the endogenously hyperscreted IL-10 is primarily responsible for the observed decrease in IL-12 released by the frozen cells . They further suggest that the increased amounts of IL-12 secreted by the irradiated PBMCs could account for the previously reported increase in IL-2 and interferon (IFN)-gamma release by the irradiated PBMCs and the radiation-induced immunopotentiation and tumor regression . Considering the pivotal role played by IL-12 in the immune system, and in antimicrobial and antitumor activities, production of only 10% of the normal levels by the frozen cells could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapy . Administration of exogenous IL-12 at the time of frozen PBMC transplantations might have a therapeutic value in these patients.

Ann Pharmacother, 1996 Oct, 30(10), 1130 - 40
A practical look at the clinical usefulness of the beta-lactam/beta-lactamase inhibitor combinations; Hart SM et al.; OBJECTIVE: To aid clinicians in developing an approach to the use of intravenous beta-lactam/beta-lactamase inhibitors on a patient-specific basis . To achieve this, the pharmacology, in vitro activity, and clinical use of the intravenous beta-lactam/beta-lactamase inhibitor combinations in the treatment of selected infections seen in hospitalized patients are discussed . DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987-1995); Index Medicus (1987-1995); program and abstracts of the 32nd (1992), 33rd (1993), 34th (1994), and 35th (1995) Interscience Conference on Antimicrobial Agents and Chemotherapy; bibliographic reviews of review articles; and package inserts . STUDY SELECTION: In vitro and in vivo studies on the pharmacokinetics, microbiology, pharmacology, and clinical effectiveness of ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam were evaluated . DATA SYNTHESIS: Many properties of the beta-lactam/beta-lactamase inhibitor combinations are similar . Differences in dosing, susceptibilities, and clinical applications are important considerations for clinicians . Potential roles for these agents in the clinical setting include pneumonia, intraabdominal infections, and soft tissue infections . A short discussion on susceptibility data interpretation is also presented . CONCLUSIONS: There are important differences among the available beta-lactam/beta-lactamase inhibitor combinations, such as spectra of activity, which need to be considered in choosing an agent for a patient-specific case . These products can be useful alternatives to conventional two- to three-drug regimens in mixed infections such as foot infections in patients with diabetes and hospital-acquired intraabdominal infections.

Antimicrob Agents Chemother, 1996 Oct, 40(10), 2392 - 8
Penetration of brodimoprim into human neutrophils and intracellular activity; Braga PC et al.; The entry of an antibiotic into phagocytes is a prerequisite for its intracellular bioactivity against susceptible facultative or obligatory intracellular microorganisms . Brodimoprim is a dimethoxybenzylpyrimidine that has recently entered into clinical use, and its uptake into and elimination from human polymorphonuclear neutrophils (PMNs), together with its effects on normal phagocytic and antimicrobial mechanisms, have been investigated . Brodimoprim uptake by PMNs was determined by a velocity-gradient centrifugation technique under various experimental conditions and was expressed as the ratio of the intracellular to the extracellular drug concentration (C/E) in comparison with the C/E of trimethoprim, which was used as a control drug . After incubation with 7.5 micrograms of brodimoprim per ml, PMNs accumulated brodimoprim (C/E, 74.43 +/- 12.35 at 30 min) more avidly than trimethoprim (C/E, 20.97 +/- 6.61 at 30 min) . The cellular uptake of brodimoprim was not affected by temperature, 2,4-dinitrophenol, or potassium fluoride and was increased with an increase in the pH of the medium . It was reduced in formaldehyde-killed PMNs . The efflux of brodimoprim was very rapid (46% after 5 min) . The liposolubility of brodimoprim was about three times that of trimethoprim, as was the uptake . Therefore, a possible passive transmembrane diffusion mechanism might be proposed . Brodimoprim did not decrease either phagocytosis or phagocyte-mediated bactericidal activity, nor did it affect oxidative burst activity, as investigated by luminol-amplified chemiluminescence . On the basis of the pharmacokinetic data for brodimoprim, the concentration of 7.5 micrograms/ml was chosen as the highest concentration attainable in serum by oral therapy, and at this concentration of brodimoprim, the amount of drug that penetrated into PMNs was able to maintain its antimicrobial activity without interfering with the functions of the PMNs.

Am J Obstet Gynecol, 1996 Oct, 175(4 Pt 1), 906 - 11
Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal membranes; Macri CJ et al.; OBJECTIVE: Our purpose was to determine whether adrenomedullin, a multifunctional regulatory peptide involved in blood flow regulation and growth stimulation and with antimicrobial activity, was a component of amniotic fluid from second-trimester human fetus and to determine the source of this peptide . STUDY DESIGN: A prospective descriptive study was performed on 134 patients undergoing amniocentesis after genetic counseling, ultrasonography, and informed consent . Adrenomedullin expression was determined by immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction in fetal membranes and with radioimmunoassay in amniotic fluids . RESULTS: Radioimmunoassay of the 134 amniotic fluid specimens revealed adrenomedullin-like immunoreactivity in all of them, ranging in concentration from 10 to 300 fmol/25 microliters (170 +/- 62 fmol/25 microliters) . Immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction further established the expression of adrenomedullin protein and messenger ribonucleic acid in fetal amniotic membranes, suggesting that this organ is the source of amniotic adrenomedullin . CONCLUSIONS: Our results clearly demonstrate the presence of adrenomedullin in second-trimester human amniotic fluid and adrenomedullin messenger ribonucleic acid and protein in amniotic membranes, suggesting that adrenomedullin is a hormone involved in the maintenance of normal pregnancy . Further studies with these molecular tools are in progress to determine the precise role of this hormone and whether adrenomedullin plays a role in the pathogenesis of various disorders of pregnancy.

J Clin Microbiol, 1996 Oct, 34(10), 2630 - 1
Modified thioglycolate medium: a simple and reliable means for detection of Trichomonas vaginalis; Poch F et al.; Despite the declining rate of sexually transmitted diseases in developed countries, trichomoniasis is still one of the most common venereal infections . While diagnosis of this condition is commonly based on the microscopic wet-mount method, culture remains the most accurate single procedure for detecting the presence of Trichomonas vaginalis in clinical samples . In the present study, the efficacy of a modified formula of the commonly available thioglycolate medium was compared with that of the standard Diamond's medium for detection of T . vaginalis in samples from 176 women with vaginal symptoms . Thioglycolate medium supplemented with yeast extract, horse serum, and antimicrobial agents was as reliable as Diamond's medium for detection of T . vaginalis in vaginal fluid samples . Modified thioglycolate medium may be used as a readily available, low-cost substitute for the standard medium for culturing T . vaginalis.

Hematol Oncol Clin North Am, 1996 Oct, 10(5), 1177 - 87
Anal neoplasia . Pathogenesis, diagnosis, and management; Northfelt DW et al.; Prolonged, severe immunodeficiency provides the necessary milieu for the emergence of anogenital neoplasia caused by human papillomaviruses . Anal neoplasia is likely to become a more common manifestation of HIV disease as patients with profound immunodeficiency, who would have succumbed to opportunistic infections earlier in the epidemic, are now surviving for extended periods of time because of increasingly effective antiretroviral, prophylactic, and antimicrobial therapies . The screening and treatment strategies described for use in HIV-infected patients with anal neoplasia are currently being investigated and refined.

J Exp Med, 1996 Oct 1, 184(4), 1349 - 55
The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin; Clemens DL et al.; Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evidence of interaction of the M . tuberculosis phagosome with the endosomal compartment has been lacking . Using the cryosection immunogold technique, we have found that the M . tuberculosis phagosome acquires exogenously added transferrin in a time-dependent fashion . Near-maximal acquisition of transferrin occurs within 15 min, kinetics of acquisition consistent with interaction of the M . tuberculosis phagosome with early endosomes . Transferrin is chased out of the M . tuberculosis phagosome by incubation of the infected macrophages in culture medium lacking human transferrin . Phagosomes containing latex beads or heat-killed M . tuberculosis, on the other hand, do not acquire staining for transferrin . These and other findings demonstrate that M . tuberculosis arrests the maturation of its phagosome at a stage at which the phagosome interacts with early and late endosomes, but not with lysosomes . The transferrin endocytic pathway potentially provides a novel route for targeting antimicrobials to the M . tuberculosis phagosome.

Surgery, 1996 Oct, 120(4), 760 - 4; discussion 764-5
Gallbladder and biliary tract candidiasis; Diebel LN et al.; BACKGROUND: The clinical significance of Candida spp isolated from the gallbladder on the biliary tract is relatively unknown . METHODS: To provide this information, patients with Candida spp isolated from gallbladder and other biliary tract sources during a 10-year period were identified through the records of our clinical microbiology laboratory . Medical records were analyzed for biliary disease causes, culture data, treatment, and outcome . RESULTS: Twenty-seven patients were identified . Five of seven patients with cholecystitis were critically ill intensive care unit (ICU) patients in whom the mortality rate was 100% . Gallstone pancreatitis was found in four patients and was fatal in one patient with a pancreatic abscess and ongoing retroperitoneal sepsis . An external biliary shunt/endoprosthesis was placed in 16 patients to relieve biliary obstruction . Cholangitis was present in 14 patients, and most bile cultures contained Candida as part of a mixed flora . Only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida at other sites . CONCLUSIONS: (1) The ICU patient with Candida cholecystitis has a grave prognosis . (2) Patients with Candida isolated from biliary stents placed for obstruction and cholangitis should be treated with both antifungal and broad spectrum antimicrobial agents . (3) Candidemia is not frequently seen in this setting.

Arch Surg, 1996 Oct, 131(10), 1054 - 60
Pancreas graft loss caused by intra-abdominal infection . A risk factor for a subsequent pancreas retransplantation; Benedetti E et al.; OBJECTIVE: To investigate whether previous pancreas graft loss caused by intra-abdominal infection is a risk factor for a subsequent pancreas retransplantation . DESIGN: Retrospective case-series analysis . SETTING: Large university hospital . PATIENTS: Of 97 pancreatic retransplantations (July 1, 1985 to June 30, 1994), 13 (13%) were performed after previous pancreas grafts had been lost because of intra-abdominal infection . MAIN OUTCOME MEASURES: Cause of retransplant graft loss; patient survival . RESULTS: Of 13 cases of pancreatic retransplantations performed after previous grafts had been lost because of intra-abdominal infection, 12 (92%) were again complicated by intra-abdominal infection . Of these 12 retransplantation infections, 10 were caused by the same microbial species that had caused failure of the previous graft 1 to 5 years earlier (8 required graft pancreatectomy {mortality rate, 25%}, and 2 were successfully treated) and 2 were caused by different microbial species (both required graft pancreatectomy {mortality rate, 0%}) . In 1 of the 13 retransplantations, prophylactic antimicrobial treatment was directed at the microbial species that had caused failure of the previous graft; no recurrent intra-abdominal infection developed . CONCLUSIONS: Intra-abdominal infection after a previous pancreas transplantation is a risk factor for recurrence of infection by the same microbial species after a subsequent retransplantation . For the selected patients who are considered for retransplantation in spite of their previous graft loss caused by intra-abdominal infection, periretransplantation antimicrobial prophylaxis should include a prolonged course of an agent directed against the previously identified microbial species.

Br J Cancer, 1996 Oct, 74(7), 1141 - 7
Phase I study of simultaneous dose escalation and schedule acceleration of cyclophosphamide-doxorubicin-etoposide using granulocyte colony-stimulating factor with or without antimicrobial prophylaxis in patients with small-cell lung cancer; Ardizzoni A et al.; A phase I study was designed to assess whether dose intensity of an 'accelerated' cyclophosphamide-doxorubicin-etoposide (CDE) regimen plus granulocyte colony-stimulating factor (G-CSF) could be increased further, in an outpatient setting, by escalating the dose of each single drug of the regimen . Patients with previously untreated small-cell lung cancer (SCLC) received escalating doses of cyclophosphamide (C) 1100-1300 mg m-2 intravenously (i.v.) on day 1, doxorubicin (D) 50-60 mg m-2 i.v . on day 1, etoposide (E) 110-130 mg m-2 i.v . on days 1, 2, 3 and every 14 days for at least three courses . Along with chemotherapy, G-CSF (filgastrim) 5 micrograms kg-1 from day 5 to day 11 was administered subcutaneously (s.c.) to all patients . Twenty-five patients were enrolled into the study . All patients at the first dose level (C 1100, D 50, E 110 x 3) completed three or more cycles at the dose and schedule planned by the protocol and no 'dose-limiting toxicity' (DLT) was seen . At the second dose level (C 1200, D 55, E 120 x 3) three out of five patients had a DLT consisting of 'granulocytopenic fever' (GCPF) . Another six patients were treated at this dose level with the addition of ciprofloxacin 500 mg twice a day and only two patients had a DLT {one episode of documented oral candidiasis and one of 'fever of unknown origin' (FUO) with generalised mucositis} . Accrual of patients proceeded to the third dose level (C 1300, D 60, E 130 x 3) with the prophylactic use of ciprofloxacin . Four out of six patients experienced a DLT consisting of GCPF or documented non-bacterial infection . Accrual of patients at the third dose level was then resumed adding to ciprofloxacin anti-fungal prophylaxis (fluconazole 100 mg daily) and anti-viral prophylaxis (acyclovir 800 mg twice a day) from day 5 to 11 . Out of five patients treated three experienced a DLT consisting of severe leucopenia and fever or infection . With a simultaneous dose escalation and schedule acceleration it is indeed possible to take maximum advantage of G-CSF activity and to increase CDE dose intensity by a factor 1.65-1.80 for a maximum of 3-4 courses . The role of antimicrobial prophylaxis in this setting deserves to be investigated further.

Biochemistry, 1996 Oct 1, 35(39), 12733 - 41
Secondary structure and location of a magainin analogue in synthetic phospholipid bilayers; Hirsh DJ et al.; Magainins are cationic, membrane-active peptides which show broad-spectrum antimicrobial activity . We have investigated the secondary structure and location of an analogue of magainin 2 in synthetic phospholipid bilayers using a combination of Fourier transform infrared (FTIR) spectroscopy and solid-state nuclear magnetic resonance (NMR) spectroscopy . Ala19-magainin 2 amide exhibits both alpha-helix and beta-sheet secondary structures in lipid bilayers containing either dipalmitoylphosphatidylglycerol (DPPG) or a 1:1 molar mixture of DPPG and dipalmitoylphosphatidylcholine (DPPC) . The combination of FTIR and solid-state NMR results suggests that there are two populations of peptide . The secondary structure of one population is alpha-helix while that of the other population is beta-sheet . We demonstrate that the solid-state NMR technique, rotational-echo double resonance (REDOR), can be used to measure both intra- and intermolecular dipole-dipole interactions in membrane-bound peptides . Our REDOR experiments indicate that alpha-helical Ala19-magainin 2 amide is bound near the phospholipid head groups.

Blood, 1996 Oct 1, 88(7), 2722 - 31
Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation; Guillemot JC et al.; The Rho subfamily of small guanosine triphosphate (GTP)-binding proteins, through their role in cytoskeletal organization, is involved in diverse cellular functions, including cell motility and morphologic changes during differentiation . Rac also has a special role in the production of superoxide, a key component in phagocytic antimicrobial function . Guanosine diphosphate (GDP)-dissociation inhibitors (GDIs) belong to one of three classes of proteins that regulate the critical cycling of GTP-binding proteins between the inactive and active states . Two homologous GDIs for the Rho subfamily have been identified . GDID4 is preferentially expressed in hematopoietic cells, while RhoGDI is ubiquitously expressed . Whether different physiologic functions are subserved by the two GDIs is unknown . We have derived embryonal stem (ES) cells with targeted disruption of both alleles of the GDID4 gene and examined hematopoiesis and phagocytic functions of macrophages derived from in vitro ES-cell differentiation . GDID4-/- ES cells develop like wild-type cells into colonies that contain heterogeneous populations of progenitor cells and differentiated erythromyeloid cells . GDID4-/- cells express no GDID4 protein, but have normal levels of RhoGDI . GDID4-/- macrophages phagocytose yeasts and antibody-opsonized erythrocytes as effectively as wild-type macrophages . However, a slight but consistent reduction in their capacity to generate superoxide was observed, which suggests new insight into the cellular role of GDID4 . The minimal phenotypic effect of a loss of function of GDID4 also indicates a significant redundancy of function between GDID4 and RhoGDI . Their functional repertoire may be better revealed by a disruption of both genes . The use of hematopoietic cells derived in vitro from genotypically altered ES cells avoids the difficulties inherent in generating knockout animals and is a useful complementary approach for evaluating the gene function.

J Virol, 1996 Oct, 70(10), 7103 - 7
Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo; Sharma DP et al.; Interleukin-4 (IL-4) promotes the growth of Th2-type cells while down regulating the development of Th1-type cells . It has been suggested that the actions of this factor inhibit Th1-type effector activity in vivo and may underlie the development of diseases normally controlled by cell-mediated immune responses . Here, we show that clearance of recombinant vaccinia viruses (VV) engineered to express the gene for murine IL-4 is markedly delayed in mice compared with control recombinant VV . While antiviral antibody levels and NK activity in mice given control virus or IL-4-expressing virus were similar, antiviral cytotoxic T-lymphocyte responses were profoundly suppressed throughout the course of infection with the latter . Limiting dilution analysis of IL-4-virus-infected spleens revealed a marked reduction in numbers of cytotoxic T-lymphocyte precursors . Furthermore, reverse transcriptase PCR analysis of splenic mRNA prepared from mice infected with the IL-4-expressing VV showed a marked down regulation of IL-12, gamma interferon, and IL-2 gene expression compared with that from mice given control virus . IL-4 also inhibited the production of nitric oxide (NO), a potent mediator of antimicrobial activity . Together, these data show that IL-4 markedly suppresses the development of antiviral cell-mediated immune responses in vivo with deleterious effects on virus clearance.

Fortschr Med, 1996 Sep 30, 114(27), 349 - 50
{Curcuma xanthorrhiza (Java tumeric) in clinical use}; Hentschel C et al.; The rhizome of Curcuma xanthorrhiza has been used for medical purposes for hundreds of years . A related plant, but which contains other constituents, is C . domestica, which is used in the manufacture of curry powder . Both experimental and clinical studies have revealed, in particular, a choleretic effect . In addition, in part in animal experimental studies, antilipidemic, analgesic-antiphlogistic and antimicrobial effects have also been found.

Eur J Biochem, 1996 Sep 15, 240(3), 532 - 9
Purification and characterization of a proline-rich antibacterial peptide, with sequence similarity to bactenecin-7, from the haemocytes of the shore crab, Carcinus maenas; Schnapp D et al.; Antibacterial peptides are important for non-specific host defence in many animals . They have been extensively characterized from mammals, amphibians, insects and chelicerates but have not so far been found in crustaceans . Here we report the presence of several constitutive antibacterial proteins, active against both gram-positive and gram-negative bacteria, in the haemocytes of the shore crab, Carcinus maenas . These proteins have molecular masses of > 70 kDa, approximately 45 kDa, approximately 14 kDa and 6.5 kDa . The 6.5 kDa peptide has been purified to homogeneity by Sep Pak C18 extraction, gel filtration and reverse-phase HPLC . Partial N-terminal sequence analysis further shows that it is proline rich and shares more than 60% identity in a 28-amino-acid overlap with the mature form of bactenecin 7, an antimicrobial peptide from bovine neutrophils which belongs to the cathelicidin family of mammalian peptide antibiotics.

Ann Intern Med, 1996 Sep 15, 125(6), 442 - 7
Piperacillin to prevent cholangitis after endoscopic retrograde cholangiopancreatography . A randomized, controlled trial; van den Hazel SJ et al.; BACKGROUND: Cholangitis does not often occur after endoscopic retrograde cholangiopancreatography (ERCP), but it can be a serious complication of this procedure . Antibiotic prophylaxis is therefore frequently used in patients having ERCP, but existing data are insufficient to allow evaluation of the effectiveness of this practice . OBJECTIVE: To determine the efficacy of single-dose antibiotic prophylaxis with piperacillin for ERCP-induced cholangitis . DESIGN: Randomized, double-blind, placebo-controlled clinical trial . SETTING: Tertiary referral center for ERCP . PATIENTS: Patients who had ERCP for suspected biliary tract stones or distal common bile duct stricture were eligible . Major exclusion criteria were previous ERCP within 7 days, biliary endoprosthesis in situ, and use of antimicrobial agents or presence of fever within 7 days before the procedure . INTERVENTION: Piperacillin, 4 g, or placebo was given intravenously approximately 30 minutes before ERCP . MEASUREMENTS: Duration of follow-up was 1 week . Acute cholangitis was diagnosed if a patient had a body temperature greater than 38 degrees C, a clinically apparent need for antibiotic treatment, and no symptoms indicating infection outside of the biliary tree . RESULTS: 551 consecutive patients were enrolled . During ERCP, stones were found in 147 patients, malignant distal strictures were found in 203 patients, other pathologic findings were seen in 88 patients, and normal biliary tracts were seen in 113 patients . Seventeen of the 281 patients who received placebo (6.0%) and 12 of the 270 patients who received piperacillin (4.4%) developed acute cholangitis (relative risk, 0.73 {95% CI, 0.36 to 1.51}) . The absolute risk reduction was 1.6% (CI, -5.3% to 2.1%) . All cases of cholangitis (with the exception of one case seen in a patient in the piperacillin group) were mild or moderate in severity . CONCLUSION: Single-dose prophylaxis with piperacillin is not associated with a clinically significant reduction in the incidence of acute cholangitis after ERCP in patients suspected of having biliary tract stones or distal common bile duct stricture.

Biochemistry, 1996 Sep 10, 35(36), 11888 - 94
Interactions of monomeric rabbit neutrophil defensins with bilayers: comparison with dimeric human defensin HNP-2; Hristova K et al.; Human antimicrobial neutrophil defensin HNP-2 has been shown to form large multimeric pores in pure 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG) bilayers that lead to all-or-none release of vesicle contents {Wimley et al . (1994) Protein Sci.3, 1362-1373} . Because human neutrophil defensins form natural dimers in solution, the question arises as to the role of dimerization in pore formation . However, the dimers are so stable that this question is not easily answered directly . Rabbit neutrophil defensins, whose three-dimensional structures are very similar to those of human defensins, are monomeric in aqueous solution and thus provide an opportunity to test the hypothesis that dimerization may play a role in multimeric pore formation . We therefore examined the interactions of the six known rabbit neutrophil defensins with large unilamellar vesicles (LUV) under the conditions known to lead to stable pore formation by HNP-2 . We find that the rabbit defensins bind strongly to LUVs formed from pure POPG or mixtures of POPG with neutral (zwitterionic) phospholipid but induce leakage of vesicle contents only from pure POPG vesicles . Rabbit defensin NP-4 does not cause leakage under any conditions examined . The remaining defensins, NP-1, NP-2, NP-3A, NP-3B, and NP-5, cause graded release of the contents of pure POPG vesicles as does a mixture of the six defensins . The graded release indicates that the rabbit defensins do not form stable pores in the membrane . This result thus suggests that the structural features of human defensins that permit dimer formation in aqueous solution are likely to be important in the formation of multimeric pores.

Ugeskr Laeger, 1996 Sep 9, 158(37), 5174 - 5
{Interaction between warfarin and nalidic acid}; Gullov AL et al.; A case of presumed interaction between warfarin and nalidixic acid is reported in an 84 year-old female in whom INR rose from 1.9 to 9.6 after start of treatment with nalidixic acid . The interaction may be caused by several factors: 1) Nalidixic acid may displace warfarin from plasma proteins and thereby increase the anticoagulant effect . 2) The fluoroquinolone drug enoxacin reduces the hepatic clearance of the R-stereomere of warfarin but without prolongation of the prothrombin time ratio . 3) Fluoroquinolones may affect the vitamin-K producing bacteria in the gut and thereby influence the vitamin-K: warfarin ratio in plasma . Only some patients develop hypoprothrombinaemia during concomitant therapy with warfarin and quinolone antimicrobials . It is hypothesized that the interaction may partly be related to age, sex or concomitant disease . Frequent control of INR in patients treated with both warfarin and quinolone antimicrobials is recommended.

BMJ, 1996 Sep 7, 313(7057), 608 - 10
Will we ever know when to treat HIV infection?
Phillips AN, Smith GD, Johnson MA.
Confidence in the efficacy of using antiretroviral drugs to treat HIV infection has grown in the past year as a result of the prolonged survival of those randomly allocated to receive an additional drug in comparative controlled trials . HIV remains, however, the only serious infectious disease for which antimicrobial treatment is deliberately delayed . This is because infected subjects can often be symptomless for more than a decade in the absence of any treatment, and results from trials with the nucleoside analogue reverse transcriptase inhibitor zidovudine have failed to show any evidence for extended survival in those beginning treatment early compared with those who deferred treatment . The new confidence in currently available treatments, and in the prospects for new ones, inevitably leads to renewed questioning of the current strategy of waiting for signs of immune deficiency before electing to intervene . A new randomised controlled trial comparing strategies of early and deferred treatment is required to assess whether the time has come for intervention immediately after HIV has been diagnosed.

J Biol Chem, 1996 Sep 6, 271(36), 21808 - 13
Innate immunity . Isolation of several cysteine-rich antimicrobial peptides from the blood of a mollusc, Mytilus edulis; Charlet M et al.; We have isolated from the blood of immune-challenged and untreated mussels (Mytilus edulis) antibacterial and antifungal peptides . We have characterized two isoforms of a novel 34-residue, cysteine-rich, peptide with potent bactericidal activity and partially characterized a novel 6.2-kDa antifungal peptide containing 12 cysteines . We report the presence of two members of the insect defensin family of antibacterial peptides and provide a phylogenetic analysis that indicates that mollusc and arthropod defensins have a common ancestry . Our data argue that circulating antimicrobial peptides represent an ancient host defense mechanism that predated the separation between molluscs and arthropods at the root of the Cambrian, about 545 million years ago.

Pharm Pract Manag Q, 1996 Oct, 16(3), 60 - 6
Developing critical pathways containing antimicrobial therapy; Hartmann RA; Today's health care institutions are being challenged to provide high quality health care in the most efficient way possible . One approach taken by many organizations has been the development of critical pathways in order to minimize delays in therapy, facilitate the best outcomes, optimize resources, and maximize quality . Opportunities exist for these protocols to address a number of antimicrobial therapy issues and the multidisciplinary development process provides an excellent opportunity for pharmacist involvement.

Pharm Pract Manag Q, 1996 Oct, 16(3), 19 - 34
Antibiotic streamlining: development and justification of an antibiotic streamlining program; Ramirez JA; Several techniques can be applied to streamline or optimize antimicrobial therapy in the hospitalized patient . As soon as there is a documented clinical response to intravenous therapy, the antibiotic can be switched to the oral route of administration . This antimicrobial streamlining technique is called switch therapy . This article presents the development of the switch therapy concept, the good clinical outcome obtained with switch therapy in patients with community and nosocomial pneumonia, as well as the cost-savings to our institution after the implementation of this program.

Biochemistry, 1996 Sep 3, 35(35), 11361 - 8
An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation; Matsuzaki K et al.; The effect of an antimicrobial peptide, magainin 2, on the flip-flop rates of phospholipids was investigated by use of fluorescent lipids, i.e., anionic N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L-alpha- phosphatidylethanolamine (NBD-PE), 1-oleoyl-2-{12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)- dodecanoyl}-L-alpha-phosphatidic acid (C12-NBD-PA), 1-oleoyl-2-{12- ((7-nitrobenz-2-oxa-1,3-diazol-4-yl)- amino)dodecanoyl}-L-alpha-phosphatidyl-L-serine (C12-NBD-PS), and zwitterionic 1-palmitoyl-2-{6-((7- nitrobenz-2-oxa-1,3-diazol-4-yl)amino)caproyl}-L-alpha-phosphatidy lcholine (C6-NBD-PC) . Their intrinsic flip-flop half-lives at 30 degrees C in the absence of the peptide were 1.1 h, ca . 7 h, ca . 8 days, and > 2 days, respectively . The peptide accelerated the flip-flop half-lives of the fluorescent lipids to an order of minutes . Furthermore, the flip-flop was coupled with the membrane permeabilization and the peptide translocation {Matsuzaki, K., Murase, O., Fujii, N., & Miyajima, K . (1995) Biochemistry 34, 6521-6526}, suggesting pore-mediated flip-flop . The flip-flop rate was independent of the initial labeling conditions (outer leaflet label or inner leaflet label) . From these results, a model was proposed, in which the lipids translocate across the membrane by lateral diffusion along the wall of the pores composed of the peptides and the lipids . A simple theoretical calculation could explain the coupling of the flip-flop with the permeabilization.

FEBS Lett, 1996 Sep 2, 392(3), 309 - 12
Unusually stable helical kink in the antimicrobial peptide--a derivative of gaegurin; Suh JY et al.; The structure of an active analog of the antibacterial peptide gaegurin was investigated by CD and NMR spectroscopy . The NOE connectivities showed that 21 out of 24 residues formed an a-helix despite the presence of a central proline . CD and NMR analysis indicates that the helix is in fast equilibrium with random coil . From chemical shift analysis of the amide protons, the distances of hydrogen bonding in the helix were calculated, and manifested obvious periodicity which implied a kink in the middle of the helix . 1D amide proton exchange experiments provided further evidence of an exceptionally stable kink . It is inferred that this kink is important not only to the function of the peptide but also to the early stage of the folding as a nucleation site.

Int Endod J, 1996 Sep, 29(5), 320 - 6
Susceptibility of Actinomyces israelii to antibiotics, sodium hypochlorite and calcium hydroxide; Barnard D et al.; Actinomyces israelii has been repeatedly implicated as a cause of failure of endodontic therapy . This study investigated the antimicrobial effect of antibiotics as well as intracanal medicaments, sodium hypochlorite solution and calcium hydroxide, on this important pathogen . Growth of A . israelii was inhibited by low concentrations of antibiotics, yet high concentrations were not bactericidal for A . israelii over 1 week . When A . israelii was exposed for 2-6 weeks at concentrations equivalent to clinical serum levels, the antibiotics were lethal . The results reveal a species-specific antibiotic tolerance for A . israelii . Both sodium hypochlorite solution and calcium hydroxide were found to be highly effective in killing A . israelii.

Med Oncol, 1996 Sep, 13(3), 133 - 40
Granulocyte-macrophage colony-stimulating factor and the immune system; Tarr PE; Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine currently used for the reversal of neutropenia associated with cytotoxic chemotherapy, bone marrow and haemopoietic stem cell transplantation . GM-CSF also modulates the function of differentiated white blood cells . In the context of local inflammatory responses, GM-CSF stimulates macrophages for antimicrobial and antitumor effects . GM-CSF further enhances healing and repair by its actions on fibroblasts and epidermal cells . GM-CSF is the pivotal mediator of the maturation and function of dendritic cells, the most important cell type for the induction of primary T cell immune responses . GM-CSF may enhance antibody dependent cellular cytotoxicity (ADCC) in several cell types, and the generation and cytotoxicity of natural killer (NK) cells . On this basis, GM-CSF may be useful for inducing or augmenting antibody responses to antimicrobial vaccines, to enhance killing of intracellular microorganisms, to accelerate epidermal and mucosal wound healing, and to stimulate protective immunity against tumors.

Zh Mikrobiol Epidemiol Immunobiol, 1996 Sep-Oct, (5), 3 - 7
{The antimicrobial activity and cytotoxicity of anti-infective preparations in a human cell-culture model}; Afinogenov GE et al.; The complex evaluation of Polysept, a new antiseptic, by its antimicrobial activity with the determination of the minimal inhibiting concentration, its antiadhesive effect and its cytotoxic action with the determination of the minimal toxic dose is presented after preclinical trial, carried out on the culture of skin and lung fibroblasts of human embryo used as an experimental model . The presence of 50% human blood serum enhances the antimicrobial and antiadhesive effects and decreases the cytotoxic action of the antiseptic with respect to fibroblasts, which makes it a promising preparation not only for the treatment, but also for prophylaxis of wound infection.

Am J Contact Dermat, 1996 Sep, 7(3), 158 - 63
Gruppo Italiano Ricerca Dermatiti da Contatto ed Ambientali Italian Multicenter Study of Allergic Contact Photodermatitis: epidemiological aspects; Pigatto PD et al.; A total of 1,050 patients with histories and clinical pictures suggestive of photoallergic contact dermatitis were seen . All the patients underwent photopatch tests with haptens proposed by the Gruppo Italiano Ricerca Dermatiti da Contatto plus other substances suggested by each patient's history . Two hundred fifty-nine patients (24.6%) were positive to at least one test substance of the standard series or to substances added . Typical photoallergic reactions were seen in 198 subjects (259 minus 40 toxic photodermatitis to chlorpromazine and 21 to promethazine), which represents 18.8% of the total population . Topical drugs represent the most involved substances in photodermatitis . The incidence in our population was about equal for antimicrobial agents, additives to fragrances, and fragrances themselves . Other allergens found were salicylanilides, whereas sun-screening agents were the fifth group of haptens but with clear-cut relevance . This study is a first attempt to organize the data about results of photopatch tests applied to Italian patients.

ASAIO J, 1996 Sep-Oct, 42(5), M763 - 5
Retrospective analysis of infection in patients undergoing support with left ventricular assist systems; Springer WE et al.; Infection is a problem in patients undergoing support with left ventricular assist systems . To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system . Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy . Of the 56 patients, 25 (41%) had an infection . Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%) . The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%) . Of the positive cultures, 84% were bacterial and 16% fungal . There were no positive viral cultures . Positive cultures from left ventricular assist system related sites made up only 8.7% of the total . All but one of the patients with device related infections survived to transplantation . The long-term survival rate for patients in this group after transplantation was 77.8% . Two patients required surgical revision of the driveline because of infection . Both were free of infection postoperatively . Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days) . In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.

J Antibiot (Tokyo), 1996 Sep, 49(9), 860 - 4
Pyrrolosporin A, a new antitumor antibiotic from Micromonospora sp . C39217-R109-7 . I . Taxonomy of producing organism, fermentation and biological activity; Lam KS et al.; Strain C39217-R109-7 (ATCC 53791) is an actinomycete strain isolated from a soil sample collected at Puerto Viejo, Peru . It produces a new antitumor antibiotic, designated pyrrolosporin A . Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Micromonospora sp . C39217-R109-7 . Pyrrolosporin A shows antimicrobial activity against Gram-positive bacteria and it is weakly active against Gram-negative bacteria . Pyrrolosporin A prolongs the life span of mice inoculated with P388 leukemia cells.

Eur J Clin Microbiol Infect Dis, 1996 Sep, 15(9), 741 - 4
First reported African case of Anaerobiospirillum succiniciproducens septicemia; Marcus L et al.; The first reported African case of septicemia caused by Anaerobiospirillum succiniciproducens is presented . The source of the infection was not identified . The clinical presentation and relative risk factors of the infection, and biochemical characteristics and antimicrobial susceptibility of the organism are described . Recommendations on appropriate antimicrobial therapy and postinfection sequelae are discussed.

QJM, 1996 Sep, 89(9), 695 - 9
Central venous catheter infections in AIDS patients receiving daily home therapy for cytomegalovirus disease; Casado JL et al.; We studied the infection rate of long-term intravenous access used for daily home treatment of cytomegalovirus (CMV) disease in 61 AIDS patients who had 75 central venous catheters implanted for antiviral maintenance therapy between February 1989 and December 1994 . In 39 patients (64%) the risk factor for AIDS was intravenous drug abuse . Sixty-three catheters were Hickman type and 12 were totally implanted ports . The cumulative follow-up time was 19000 catheter-days (52 patient-years), with median duration of placement of 249 days . The infection rate was 0.22 infections per 100 catheter days . The probability of remaining free of catheter-related sepsis was 58% at 6 months . In 25 cases (61%) antimicrobial therapy without catheter removal was successful . Three patients died because of a catheter-related infection (mortality rate 7.3%) . Infection-free survival time was not related to the risk factor for AIDS (p = 0.44) or type of device (p = 0.41) . The total infection rate in these patients receiving daily home maintenance therapy for CMV disease through a long-term catheter was similar to that in other AIDS patients receiving weekly treatment in hospital facilities.

J Dent, 1996 Sep, 24(5), 345 - 8
Oral species of Fusobacterium from human and environmental samples; Gaetti-Jardim E Jr et al.; PURPOSE: The aim of this study was the characterization and identification of oral Fusobacterium in patients with and without periodontal disease, and from spittoons and air-water syringes . The antimicrobial susceptibility of this bacterium was evaluated . METHOD: Subgingival samples were taken using sterilized absorbent paper points . Spittoon samples were collected using sterile swabs around the drain area with shut off, and air-water syringe samples by washing the tip with Ringer solution . Samples were transferred in tubes under CO2 flux . Diluted samples were inoculated on to Omata and Disraely agar and blood agar plates, which were incubated in anaerobiosis, at 37 degrees C, for 4 days . Bacterial species were identified biochemically . MIC was determined using an agar dilution method . RESULTS: Periodontal patients, healthy subjects, spittoons and air-water syringes were 80%, 67.6%, 37.8% and 3.3% positive to Fusobacterium, respectively . Clindamycin, imipenem, lincomycin, metronidazole and tetracycline were active against all human and environmental isolates . Eighteen isolates resistant to ampicillin or penicillin G produced beta-lactamases . The presence of human oral bacteria in items of dental equipment supports the hypothesis that such equipment may serve as a vehicle for the transmission of pathogenic organisms . CONCLUSION: Pieces of dental equipment may serve as a vehicle for the transmission of oral pathogenic organisms.

Intensive Care Med, 1996 Sep, 22(9), 916 - 22
Diagnostic and therapeutic implications of transesophageal echocardiography in medical ICU patients with unexplained shock, hypoxemia, or suspected endocarditis; Slama MA et al.; OBJECTIVE: To evaluate the diagnostic and therapeutic implications of transesophageal echocardiography (TEE) in intensive care patients . DESIGN: Comparative study . SETTING: A 10-bed general intensive care unit . PATIENTS: Between 1 January 1992 and 31 May 1993, 61 patients prospectively identified with shock (n = 14), severe, unexplained hypoxemia (Partial pressure of oxygen in arterial blood/fractional inspired oxygen < 200) (n = 31), or suspected endocarditis (n = 16) underwent a TEE examination to supplement transthoracic echocardiography (TTE) examination . INTERVENTIONS: The results of each TEE examination were compared with the clinical findings and TTE data . TEE examinations were classified as follows: 0, TEE results were similar to TTE results; 00, TEE examination resulted in exclusion of suspected abnormalities; 1, TEE revealed a new but minor diagnosis compared to the TTE diagnosis; 2, TEE revealed a new major diagnosis not requiring a change of treatment; 3, TEE results revealed a new major diagnosis requiring an immediate change of treatment . RESULTS: Intraobserver reliability of the TEE classification was confirmed by a 100% concordance and interobserver reliability was evaluated as an 84% concordance . Results of the TEE classification were: class 0, n = 21 (34%); class 00, n = 13 (21%); class 1, n = 7 (12%); class 2, n = 8 (13%); class 3, n = 12 (20%) . Therapeutic implications of TEE in class 3 patients were cardiac surgery in 5 patients (2 cases of acute mitral regurgitation, 2 valvular abscesses, and 1 hematoma compressing the left atrium), discontinuation of positive end-expiratory pressure in 1 ventilated patient with an atrial septal defect, weaning off mechanical ventilation in 1 patient with an atrial septal defect, prescription of antimicrobial therapy in 3 patients with endocarditis, and prescription of anticoagulant therapy in 2 patients with left atrial thrombus . No difficulty inserting the transducer was observed in any of the 61 patients studied . The only noteworthy complication was a case of spontaneously resolving atrial fibrillation . CONCLUSION: TEE is safe and well tolerated and is useful in the management of patients in the intensive care unit with shock, unexplained and severe hypoxemia, or suspected endocarditis when TTE is inconclusive.

Ann Trop Paediatr, 1996 Sep, 16(3), 199 - 201
Neonatal meningitis due to Moraxella catarrhalis and review of the literature; Daoud A et al.; Moraxella catarrhalis has been reported with increasing frequency to be the aetiological agent of serious systemic infection in both children and adults . The first case of neonatal meningitis due to this organism is described herein . The fatal outcome and causes of failure of response to antimicrobial therapy are also discussed . A brief review of the literature describing the disease entities with which M . catarrhalis has been associated is presented.

Neurobiol Aging, 1996 Sep-Oct, 17(5), 753 - 9
Expression of CAP37, a novel inflammatory mediator, in Alzheimer's disease; Pereira HA et al.; Recent evidence suggests that inflammation in the central nervous system plays an important role in the pathogenesis of Alzheimer's disease . However, the identity of the inflammatory mediators, cytokines, and reactive oxygen species, that orchestrate cell death and plaque biogenesis in Alzheimer's disease, have yet to be elucidated . We have identified a novel inflammatory mediator, CAP37 (Cationic Antimicrobial Protein Mi 37 kDa), that promotes mononuclear cell chemotaxis, adhesion of monocytes to endothelium, and release of oxygen radicals from monocytes . In the present immunocytochemical study, we demonstrate the expression of CAP37 in the cerebral microvasculature in Alzheimer's disease . CAP37 was not detected in brain vessels of normal controls or patients with other neuropathologic conditions such as Pick's, Parkinson's, Binswanger's disease, Progressive Supranuclear Palsy, and Candida infection . Treatment of cerebral endothelial cultures with inflammatory mediators, cytokines or beta-amyloid results in the induction of CAP37 expression . These in vitro data showing endothelial-CAP37 expression after beta-amyloid treatment together with the previous demonstration that CAP37 stimulates mononuclear cell migration and activation, suggest that CAP37 could contribute to neuronal injury in Alzheimer's disease.

J Antimicrob Chemother, 1996 Sep, 38(3), 457 - 63
Formulation of 'idealized' topical antimicrobial mixtures for use with cultured skin grafts; Holder IA et al.; In order to develop antimicrobial mixtures which provide broad-spectrum antimicrobial activity for use with cultured cell autografts, several individual antimicrobial agents, in concentrations non-toxic for cells in culture, were tested against a variety of bacteria and Candida spp . isolated from burn patients . An agar well diffusion topical assay was used . Antimicrobials active against Gram-positive and Gram-negative bacteria and antifungal agents, individually, were uniformly effective against their respective spectra of organisms . Broad-spectrum antibacterials were uniformly effective against Gram-negative bacteria but their activity varied against Gram-positive bacteria . Adding an agent active against Gram-positive bacteria to all broad spectrum antibacterial agents conferred uniform Gram-positive activity to the mixture . One mixture consisting of specific Gram-negative, Gram-positive and broad spectrum antibacterial agents, was uniformly active against all bacteria tested and the addition of antifungal agents extended the activity to cover Candida spp . without interfering with the mixture's overall antibacterial activity . Another mixture showed either additive or antagonistic activities against the battery of microorganisms tested . Thus, these methods can be used to identify mixtures of antimicrobials, in concentrations non-toxic for cells in culture, that have very broad spectra of antimicrobial activity . Such mixtures should be evaluated in patients when cultured skin grafts are used.

J Antimicrob Chemother, 1996 Sep, 38(3), 399 - 408
In-vitro activity of macrolides alone and in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine against Cryptosporidium parvum; Giacometti A et al.; The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients . The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C . The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of azithromycin, clarithromycin, roxithromycin, spiramycin, alone or in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine . Most of the agents had an inhibitory effect on parasite growth, but only at high concentrations . No agent was able to inhibit parasite growth completely, even at the highest concentrations used . The more effective agents, azithromycin, clarithromycin, roxithromycin, minocycline and pyrimethamine, produced no more than a 13.1-27.8% reduction in oocyst count and no more than a 15.1-35.7% in schizont count . Positive interaction was clearly demonstrated when macrolides were tested in combination with minocycline or pyrimethamine.

J Antimicrob Chemother, 1996 Sep, 38(3), 349 - 62
The riminophenazines, clofazimine and B669, inhibit potassium transport in gram-positive bacteria by a lysophospholipid-dependent mechanism; De Bruyn EE et al.; The effects of the riminophenazine antimicrobial agents clofazimine and B669 as well as those of lysophosphatidylcholine (LPC), on microbial K(+)-transporting systems were investigated in a range of Gram-positive and Gram-negative bacteria using 42K and 86Rubidium (86Rb) as tracers . Exposing the Gram-positive bacteria to 0.1-10 mg/L of the drugs resulted in a dose-related inhibition of uptake of both radiolabelled cations due primarily to the inhibition of their influx which was prevented by pretreating the microorganisms with 25 mg/L alpha-tocopherol (vitamin E) which forms a complex with lysophospholipids . In contrast, Gram-negative bacteria were resistant to riminophenazine-mediated inhibition of K(+)-transport, with only one of four well-characterised K(+)-transport system mutants of Escherichia coli, namely Kup, being affected by the antimicrobial agents . The selective antimicrobial activity of riminophenazines against Gram-positive bacteria is probably achieved by lysophospholipid-mediated inactivation of K(+)-transport, while Gram-negative microorganisms possess several K(+)-transport systems which are either inaccessible and/or insensitive to lysophospholipids . Thus, K(+)-transport systems may represent novel targets for antimicrobial agents.

Int J Urol, 1996 Sep, 3(5), 402 - 4; discussion 405
Pyogenic vertebral osteomyelitis after acute bacterial prostatitis: a case report; Soda T et al.; A case of pyogenic vertebral osteomyelitis after acute bacterial prostatitis in a 78-year-old man is reported . The rarity and subtle clinical presentation of this condition, and the delayed appearance of radiologic signs of progression to destructive osteomyelitis, contributed to a significant delay in diagnosis . An arterial blood culture positive for bacterial growth during the episode of acute prostatitis suggested that bacteremia might result from hematogenous spread of the infection to the vertebral column via the venous system . Since intensive antimicrobial therapy proved ineffective, debridement of the first and second lumbar vertebral bodies, and anterior spinal fusion from the twelfth thoracic to the third lumbar vertebrae were performed . The patient's high fever and severe lumbago subsided immediately after the surgery . The possibility of development to pyogenic vertebral osteomyelitis should be kept in mind when treating a serious genitourinary tract infection.

J Periodontol, 1996 Sep, 67(9), 866 - 70
The effect of subgingival antimicrobial therapy on the levels of stromelysin and tissue inhibitor of metalloproteinases in gingival crevicular fluid; Pourtaghi N et al.; Recent investigations imply that a key mechanism in the pathogenesis of periodontal disease may be the ability of oral microorganisms to induce production and/or activation of matrix metalloproteinases (MMPs) in the host tissues . It has been suggested that the pharmacologic inhibition of MMP activity could play an important role in achieving a desirable outcome in periodontal therapy . The efficacy of locally delivered antibiotics on the level of gingival crevicular fluid (GCF) stromelysin (SL) and tissue inhibitor of metalloproteinases (TIMP) on sites with a history of a poor response to mechanical treatment was studied . Fifty-two patients with 4 periodontal pockets > or = 5 mm and bleeding on probing were randomized into four groups of 13 patients . One group received scaling and root planing alone and the other three groups received scaling and root planing plus a locally delivered antimicrobial system . These included 25% tetracycline fiber, 2% minocycline gel, and 25% metronidazole gel . The GCF samples taken at baseline and 6 weeks after treatments were analyzed using an enzyme linked immunosorbent assay (ELISA) . GCF SL levels significantly decreased after adjunctive tetracycline fiber (paired t-test, P = 0.020) and minocycline gel (paired t-test, P = 0.023) treatments whereas it remained almost unchanged in the other two groups . While the GCF TIMP level did not change significantly in the scaling and root planing alone group, it significantly increased for all three adjunctive antimicrobial treatments (for tetracycline fiber P < 0.001, minocycline gel P = 0.005, metronidazole gel P < 0.001) . The use of adjunctive locally delivered antimicrobial systems, particularly the tetracycline family, may offer an advantage in changing the metalloproteinase profile of the GCF to one more compatible with periodontal health.

J Periodontol, 1996 Sep, 67(9), 860 - 5
Comparison of 3 periodontal local antibiotic therapies in persistent periodontal pockets; Radvar M et al.; The aim of this study was to evaluate the efficacy of 3 commercially available periodontal systems for local delivery of antibiotics as adjuncts to scaling and root planing in treatment of sites with persistent periodontal lesions following a course of scaling and root planing . Fifty-four patients with 4 pockets > or = 5 mm and bleeding on probing and/or suppuration were randomized in 4 treatment groups including: scaling and root planing plus application of 25% tetracycline fiber (S + Tet) (13 patients), scaling and root planing plus application of 2% minocycline gel (S + Min) (14 patients), scaling and root planing plus application of 25% metronidazole gel (S + Met) (14 patients), and scaling and root planing alone (S) (13 patients) . Clinical measurements were taken at baseline and 6 weeks after the end of treatment periods . All treatments were applied using the distributors' recommended protocols and resulted in significant improvement in probing depth, attachment level, bleeding on probing and the modified gingival index (MGI) scores . The improvements in clinical parameters were greater in all three adjunctive treatment groups than scaling and root planing alone . The mean probing depth reductions were: S + Tet = 1.35 mm, S + Met = 0.95 mm, S + Min = 0.87 mm and S = 0.60 mm . The probing depth reduction was significantly greater in the scaling plus tetracycline fiber group than the scaling and root planing alone group (P = 0.002) . The difference between groups in improvement of attachment level or bleeding on probing was not significant Scaling plus tetracycline fiber treatment resulted in the greatest reduction in the MGI scores which was significantly greater than all other groups . While the frequency of sites with suppuration was markedly reduced following all treatments, it reached zero in the scaling plus tetracycline fiber group . No serious adverse effects were observed or reported for any treatment . While all three locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regimen of scaling and root planing plus tetracycline fiber replacement gave the greatest advantage in the treatment of persistent periodontal lesions at least during the 6-week period following treatment.

Clin Nephrol, 1996 Sep, 46(3), 187 - 92
Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose; Perazella MA et al.; Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity . As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased . A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed . Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia . Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion . Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis . A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy . Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia . Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Clin Infect Dis, 1996 Sep, 23(3), 577 - 84
Invasive pneumococcal disease: clinical features, serotypes, and antimicrobial resistance patterns in cases involving patients with and without human immunodeficiency virus infection; Frankel RE et al.; We reviewed 153 episodes of invasive pneumococcal disease involving 147 hospitalized patients with and without human immunodeficiency virus (HIV) disease to examine and compare epidemiologic and clinical features, capsular serotypes, and antibiotic susceptibility patterns . HIV infection was the most common risk factor for invasive pneumococcal disease . Pneumococcal disease in HIV-infected individuals was characterized by the greater frequency with which pneumonia was the source of bacteremia (90% vs . 63%) (P < .01) and an increased recurrence rate (15% vs . < 1%) (P < .01) . The overall mortality rate was 12% and did not vary by HIV serostatus . Capsular-type data were available for 149 episodes; 90% of the types were among those found in the polyvalent pneumococcal vaccine . The four most common capsular types causing invasive disease were 14, 6b, 9v, and 22f; capsular type 9v was significantly more common among HIV-infected patients (P < .01) . Penicillin-resistant isolates were identified in 7.2% of all cases, and their presence did not vary by HIV status; 20% of isolates from cerebrospinal fluid were resistant . The majority of the resistant isolates were of capsular type 9v . Given the worldwide increase in both HIV and penicillin-resistant pneumococcal infections, better preventative and therapeutic strategies are greatly needed.

Clin Infect Dis, 1996 Sep, 23(3), 486 - 94
Emergence of antibiotic-resistant bacteria in cases of peritonitis after intraabdominal surgery affects the efficacy of empirical antimicrobial therapy; Montravers P et al.; In cases of community-acquired peritonitis, the adequacy of emprical antibiotic treatment has been shown to attenuate mortality and morbidity . The impact of empirical antibiotics on the outcome of postoperative peritonitis has never been evaluated . This study included 100 consecutively studied patients with postoperative peritonitis . The adequacy of emprical treatment was determined by means of culture and susceptibility data obtained at the time of reoperation, and the effect of such treatment on outcome was evaluated . One hundred resistant pathogens were isolated from 70 patients, of whom 45% died; by comparison, mortality among those from whom susceptible organisms were isolated was 16% (P < .05) . Inadequate empirical treatment was administered to 54 patients and was associated with poorer outcome (P < or = .05) . The outcome of postoperative peritonitis is affected by the choice and adequacy of the initial empirical antibiotic therapy . Late changes in antibiotic therapy based on culture results did not affect outcome when the initial regimen was inadequate.

Ann Pharmacother, 1996 Sep, 30(9), 972 - 7
Pharmacologic considerations for antiviral drug development; Fletcher CV; OBJECTIVE: To discuss pharmacologic considerations for the development of antiviral agents . DATA SOURCES: English-language literature pertaining to the development and clinical evaluation of antiviral compounds, primarily agents targeted against herpes group viruses and HIV . STUDY SELECTION AND DATA EXTRACTION: Pertinent information, as judged by the author, was selected for discussion . DATA SYNTHESIS: Drug development of antiviral agents presents unique problems compared with that of antimicrobial and other agents . Understanding the mechanism of action and both pharmacokinetic and pharmacodynamic considerations is critical to developing a rational dosing strategy and safe, effective use . The lack of standardized methods for antiviral susceptibility testing and the influence of factors such as strain of virus, host cell type, culture medium, inoculum size, end point, and method of measurement on the results obtained illustrate factors that complicate preclinical pharmacologic analysis of antiviral agents . Acyclovir offers a model for clinical drug development . Its mechanism of action, pharmacokinetics, and pharmacodynamics have been studied extensively . Rational guidelines for usage are available, including guidelines in special patient populations such as kidney transplant recipients and neonates . A pregnancy registry has allowed evaluation of the incidence of birth defects in fetuses exposed to systemic acyclovir . Several pitfalls in antiviral drug development are associated with inadequate pharmacologic information . The development of dextran sulfate and fialuridine provides two examples . Integration of pharmacokinetic and pharmacodynamic analyses using modern sampling and analysis techniques may facilitate more rapid development of antiviral agents and more informed dosage regimens to achieve the highest probability of therapeutic success.

Chemotherapy, 1996 Sep-Oct, 42(5), 315 - 7
Activity of east African medicinal plants against Helicobacter pylori; Fabry W et al.; The activity of extracts from the East African medicinal plants Entada abyssinica (stem bark), Terminalia spinosa (young branches), Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (leaves and stem bark) and Spilanthes mauritiana (roots and flowers) were evaluated against 12 strains of Helicobacter pylori . The most active extracts were those derived from T . spinosa with an MIC50 of 125 micrograms/ml, an MIC90 of 250 micrograms/ml and an MIC range of 62.5-500 micrograms/ml . An MIC50 of 250 micrograms/ml and an MIC90 of > 4,000 micrograms/ml was reached by H . abyssinica with a range of 125-->4,000 micrograms/ml and by X . caffra with a range of 62.5-->4,000 micrograms/ml, respectively . It is concluded that these plants contain compounds with antimicrobial activity against H . pylori.

Am J Health Syst Pharm, 1996 Sep 1, 53(17), 2054 - 62
Benchmark analysis of strategies hospitals use to control antimicrobial expenditures; Rifenburg RP et al.; Hospital expenditures on antimicrobial drugs, antimicrobial management practices, and the effects of these practices were studied . A survey on institutional budget, size, and staffing; intensive care unit drug costs and use evaluations; and pharmacy expenditures, including antimicrobial costs, for 1993 and 1994 was sent to 122 hospitals . The written survey was followed by telephoned questions regarding each institution's antimicrobial management and expenditures, and any perceived link between the two . Hospitals were grouped by size and type, data were normalized to costs per occupied bed and costs per occupied bed per case mix index, and averages for each size category were calculated for general institutional information and expenses per antimicrobial . Eighty-eight institutions (72%) responded . Although 61% to 74% of the respondents used an antimicrobial formulary to restrict drug choices and control costs, average total antimicrobial expenses increased by more than $300 per occupied bed between 1993 and 1994 . Only 7% of the institutions saw decreased costs of $500 or more per occupied bed . The most common reasons for these decreases were restructuring of pricing contracts and implementation of educational programs . The replacement of one formulary alternative with another led to increases in the use of antimicrobials other than the replacement drug and often did not produce savings . The replacement of one formulary antimicrobial with another led more to costshifting than to overall savings.

Ophthal Plast Reconstr Surg, 1996 Sep, 12(3), 218 - 22
Dog bite-induced canalicular lacerations: a review of 17 cases; Slonim CB; Canalicular lacerations are frequently found in conjunction with other facial lacerations occurring in dog bite injuries . A review of the treatment of 17 dog bite-induced canalicular lacerations is presented . Certain pathogens commonly found in the canine oral flora may cause severe secondary infections, which may result in sepsis and even death . These pathogens are reviewed along with a description of appropriate plans for antimicrobial prophylaxis . A surgical approach to such injuries is described.

Head Neck, 1996 Sep-Oct, 18(5), 399 - 404
Short-term versus long-term antimicrobial prophylaxis in oncologic head and neck surgery; Righi M et al.; BACKGROUND: Although antimicrobial prophylaxis is mandatory in major clean-contaminated oncologic surgery of the head and neck, both the choice of specific antimicrobial compounds and the treatment duration are still discussed . METHODS: A prospective, randomized trial was carried out to compare efficacy and tolerability of clindamycin-cefonicid administered for 1 day versus 3 days in reducing the rate of wound and systemic infections . The following potential risk factors for surgical wound infection were evaluated: type of surgery, stage of disease, preoperative tracheostomy, preoperative radiotherapy, and diabetes mellitus . RESULTS: One-hundred sixty-two patients were evaluable; 81 received 1-day chemoprophylaxis, while the remaining 81 were treated according to the 3-day schedule . During the first 20 days after surgery, wound infections occurred in 2 (2.5%) and 3(3.7%) patients, respectively, in the 1-day and 3-day treatment groups, so that no significant difference was found among the two evaluated chemoprophylaxis schedules . CONCLUSION: A 3-day schedule did not prove useful in preventing wound and systemic infections . All presumed risk factors were not associated with an increased rate of wound infections, although preoperative radiotherapy was associated with a greater severity of infections and a higher risk of late wound complications.

Eur J Biochem, 1996 Sep 1, 240(2), 352 - 7
Intramolecular disulfide bonds enhance the antimicrobial and lytic activities of protegrins at physiological sodium chloride concentrations; Harwig SS et al.; Protegrins are 2-kDa antimicrobial peptides that contain 16-18 amino acid residues and two intramolecular disulfide bonds . We studied the contribution of these disulfide bonds to the bactericidal activity of protegrins in physiological concentrations of NaCl by comparing protegrin PG-1 with variants that lacked one or both cysteine disulfides . Whereas the bactericidal and liposome-lytic properties of protegrin PG-1 were enhanced by adding 100 mM NaCl to the phosphate-buffered medium, NaCl addition strongly inhibited the effects of its linearized, disulfide-free variant, {A6, A8, A13, A15}protegrin-1 . Whereas protegrin PG-1 manifested beta-sheet structure by CD (circular dichroism) and ATR-FTIR (attenuated-total-reflectance-Fourier-transform-infrared) spectroscopy in buffer or membrane-mimetic environments, {A6, A8, A13, A15}protegrin-1 manifested disordered structure in phosphate buffer and alpha-helical characteristics in membrane-mimetic environments . Both single-disulfide protegrin variants, {A8, A13}protegrin-1 and {A6, A15}protegrin-1, assumed beta-sheet conformations with liposomes that simulated bacterial membranes, and both retained substantial bactericidal activity when 100 mM NaCl was present . These findings demonstrate that the intramolecular disulfide bonds of protegrins are required for their antiparallel beta-sheet conformation in membrane-mimetic environments and for their potent antimicrobial activity in media containing NaCl concentrations comparable to those found in serum and extracellular fluids.

FASEB J, 1996 Sep, 10(11), 1280 - 9
Paneth cell defensins: endogenous peptide components of intestinal host defense; Ouellette AJ et al.; Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkuhn in the small intestine of many mammalian species . These secretory cells contribute to mucosal barrier function by the apical release of granules containing a variety of antimicrobial products, including peptides termed cryptdins, for crypt defensins . In mice, six Paneth cell defensins have been characterized at the peptide level that have potent antimicrobial activities equivalent to or greater than that of rabbit neutrophil defensin NP-1 . Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high degree of specificity against certain target microorganisms . Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans . Human Paneth cells contain high levels of two different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data . The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestinal axis, and cryptdin genes are active in the intestinal epithelium prior to Paneth cell differentiation . Accordingly, Paneth cell defensins are early markers of crypt ontogeny and are therefore useful in studies of lineage determination in the intestinal epithelium . Because cryptdins mediate innate immunity in the hostile environment of the intestinal lumen, it should be of interest to define biochemical and biophysical attributes that adapt these peptides to barrier function of mucosal surfaces.

J Leukoc Biol, 1996 Sep, 60(3), 415 - 22
CAP37, a neutrophil granule-derived protein stimulates protein kinase C activity in endothelial cells; Pereira HA et al.; CAP37 is a multifunctional protein isolated from human neutrophils with important implications in host defense and inflammation . It is antimicrobial, mediates monocyte chemotaxis, and binds endotoxin . The interaction of neutrophils with endothelial cells is a central feature in inflammation . The object of this study was to determine whether CAP37, a neutrophil-derived protein, could regulate vascular endothelial cell protein kinase C (PKC), an important signaling enzyme . We found that CAP37 stimulated endothelial PKC activity in both a time- and dose-dependent fashion . This stimulation was comparable in magnitude to that evoked by phorbol myristate acetate . A monospecific antiserum against CAP37 inhibited CAP37-induced PKC activity . To establish a structural basis for this activity, overlapping peptides, based on the sequence of native CAP37 were synthesized . Maximum PKC stimulation was evoked by a peptide corresponding to amino acids 95-122 of native CAP37 . This domain was distinct from the antibiotic and endotoxin binding domain of the molecule, which resides between amino acids 20 and 44 . These data demonstrate that CAP37 can alter endothelial cell PKC and suggest that CAP37 may play a role in neutrophil-endothelial interactions.

Am J Clin Pathol, 1996 Sep, 106(3), 275 - 81
United States geographic bacteria susceptibility patterns . 1995 ASCP Susceptibility Testing Group; Quantitative analysis of a presence/absence microbiological assay: the hard surface carrier test of disinfectant efficacy; Department of Mathematical Sciences, Montana State University, Bozeman 59717, USAThe Hard Surface Carrier Test (HSCT) is a presence/absence assay for determining the extent to which chemical disinfectants kill bacteria . The disinfectants are marketed for cleaning surfaces in hospitals, restaurants, the home, etc . In the HSCT, a presence response (or equivalently, a positive carrier) is recorded if one or more bacteria survive among M bacteria attached to a glass carrier and exposed to the chemical disinfectant; otherwise, the response is absence . The presence or absence response is observed for each of many (usually 60) glass carriers and the disinfectant is considered effective if few (e.g., < or = 5%) of the carriers are positive . It would be more satisfactory to microbiologists if effectiveness were based on the fraction of bacteria that survive exposure; denote the expected survival fraction by phi . An equivalent parameter commonly used in antimicrobial research is the log-reduction, denoted by psi, where psi = -log10(phi) . Although the number M of bacteria on each exposed carrier is not known, this paper shows it is possible to estimate psi . The suggested estimator is based on the assumption that M follows a gamma distribution . The gamma parameters are estimated using counts of bacteria on the HSCT nonexposed (control) carriers . This paper provides a formula for the standard error of the estimate, a computer simulation technique for calculating the lower confidence limit, and a computer simulation study of these statistical methods.

Crit Care Med, 1996 Sep, 24(9), 1441 - 7
International sepsis trial (INTERSEPT): role and impact of a clinical evaluation committee; Sprung CL et al.; OBJECTIVE: Several large clinical trials have recently evaluated a variety of potential therapeutic interventions for sepsis and have yielded negative results based on analyses of intention-to-treat cohorts . The present study was undertaken to evaluate the importance of a Clinical Evaluation Committee . DESIGN: Prospective, double-blind evaluation of a prospective, controlled, double-blind, randomized, multinational trial . SETTING: Forty medical centers . PATIENTS: Five hundred fifty-three infused patients with severe sepsis and septic shock . METHODS: As part of an international trial (INTERSEPT) of antitumor necrosis factor therapy, a Scientific Extramural Review Committee prospectively defined and excluded patients with confounding events that objectively interfered with the potential of any intervention for sepsis to exercise its therapeutic effect . These confounding events included inappropriate antimicrobial therapy, inadequate medical-surgical management, underlying disorders, and forgoing life-sustaining therapies before management had failed . Patients who met all inclusion and exclusion criteria and who had no confounding events were defined as the Scientific Extramural Review Committee group . MEASUREMENTS AND MAIN RESULTS: Five hundred fifty-three patients were enrolled in INTERSEPT . Seventy-seven patients did not meet inclusion and exclusion criteria . Sixty patients had confounding events, including inappropriate antimicrobial therapy (n = 28), inadequate medical-surgical management (n = 16), underlying disorders (n = 17), and forgoing life-sustaining therapies (n = 7) . Four hundred sixteen patients were in the Scientific Extramural Review Committee group and their mortality rates were different from the mortality rates of the intent-to-treat cohort . In the intent-to-treat analysis among shock patients, low-dose anti-tumor necrosis factor reduced 28-day mortality by 14.5% (p = .34), whereas in the Scientific Extramural Review Committee group, the study drug reduced mortality by 26.5% (p = .16) . More patients in the high dose anti-tumor necrosis factor treatment arm (31/176) were in the invalid Scientific Extramural Review Committee group than in the other two arms (16/157 and 13/143, respectively, p < .05) . CONCLUSIONS: In large trials of sepsis, in addition to analyzing the intent-to-treat cohort, patients in compliance with the protocol and with no confounding events should also be analyzed . These results should assist in determining whether treatment groups are comparable and provide a greater likelihood of demonstrating the potential efficacy of a new therapy for sepsis . A Clinical Evaluation Committee is important to properly assess a clinical sepsis trial.

Appl Environ Microbiol, 1996 Sep, 62(9), 3521 - 6
A quantitative method to evaluate neutralizer toxicity against Acanthamoeba castellanii; Buck SL et al.; A standard methodology for quantitatively evaluating neutralizer toxicity against Acanthamoeba castellanii does not exist . The objective of this study was to provide a quantitative method for evaluating neutralizer toxicity against A . castellanii . Two methods were evaluated . A quantitative microtiter method for enumerating A . castellanii was evaluated by a 50% lethal dose endpoint method . The microtiter method was compared with the hemacytometer count method . A method for determining the toxicity of neutralizers for antimicrobial agents to A . castellanii was also evaluated . The toxicity to A . castellanii of Dey-Engley neutralizing broth was compared with Page's saline . The microtiter viable cell counts were lower than predicted by the hemacytometer counts . However, the microtiter method gives more reliable counts of viable cells . Dey-Engley neutralizing medium was not toxic to A . castellanii . The method presented gives consistent, reliable results and is simple compared with previous methods.

J Am Vet Med Assoc, 1996 Sep 1, 209(5), 954 - 7
Topical treatment of Pseudomonas sp-infected corneal ulcers in horses: 70 cases (1977-1994); Sweeney CR et al.; OBJECTIVE: To determine which antimicrobial agents were most effective against Pseudomonas sp-infected ulcerative keratitis, and identify any trends in the various clinical conditions associated with these bacteria that might assist in effective treatment of the disease . DESIGN: Retrospective case series . ANIMALS: 66 horses with 70 Pseudomonas sp-infected corneal ulcers . PROCEDURE: We reviewed medical records of horses admitted to the George D . Widener Hospital for Large Animals, University of Pennsylvania between July 1977 and December 1994 . Records of horses that had Pseudomonas sp isolated from a corneal ulcer scraping or deep swab were included in the study . RESULTS: Aggressive topical medical treatment was successful in 57 ulcers and most likely would have been effective in 5 additional ulcers . Antimicrobial susceptibility testing indicated susceptibilities of 87, 85, and 93% to tobramycin, gentamicin, and amikacin, respectively . Although concurrent fungal infections were identified in only 2 of 35 ulcers examined, almost three fourths of the ulcers were treated with antifungal medications prophylactically . Clinical outcomes of the 70 affected eyes included: excellent vision with minimal leukoma, 73%; enucleation, 19%; blind phthisical eye, 4%; peripheral vision only, 3%; and euthanasia of newborn, 1% . CLINICAL IMPLICATIONS: Aggressive topical medication with microbial agents effective against Pseudomonas sp can result in excellent vision with minimal leukoma in most horses with corneal ulcers.

Arch Surg, 1996 Sep, 131(9), 990 - 3; discussion 994
Do surgeons have a role as infectious disease consultants?
Cohn SM, Fisher BT.
BACKGROUND: Antibiotic drug restriction policies have become widespread in North America hospitals mandating medical infectious disease consultation for use of routine antimicrobial agents . OBJECTIVE: To determine physician and institutional attitudes regarding the credibility of surgeons in the area of infectious disease . DESIGN: A survey of the Surgical Infectious Disease Society (SIS) membership . PARTICIPANTS: Members of the SIS practicing in the United States and Canada (n = 464) were sent a simple opinion poll regarding surgical infectious disease specialists . After receiving the survey, the SIS members were given approximately 4 weeks to anonymously complete the questionnaire and return it to our office . RESULTS: Responses were received from 198 SIS members (43%) . Most were from large (> 400 bed) institutions (63%), and the majority of them were from university centers (76%) . Predictably, 86% of the respondents were in full-time academic practice . Some SIS respondents (21%) had undergone special training in infectious disease, and of these, 63% actually had completed a formal surgical infectious disease fellowship . Antibiotic restriction policies were nearly universal and required in 87% of institutions . Only 44% of surgeons in these hospitals, however, were privileged to release antibiotic drugs . Medical infectious disease physicians recognized surgical expertise in infectious disease in few instances (32%) . The great majority of responding SIS members (81%) believed that an examination or certification in infectious disease for surgeons was not warranted . CONCLUSIONS: Antibiotic drug restriction is prevalent in North America, and medical infectious disease specialists do not generally recognize surgical expertise in the area of infectious disease . Despite this environment, responding SIS members believe that special credentialing of surgeons in the area of infectious disease is unnecessary.

J Am Coll Surg, 1996 Sep, 183(3), 195 - 200
Polymer-iodine inactivation of the human immunodeficiency virus; Shikani AH et al.; BACKGROUND: Hospital and laboratory equipment that come in contact with body fluids of patients with human immunodeficiency virus (HIV) are potentially infective and require special measures for decontamination and disposal . Human immunodeficiency virus is sensitive to several chemicals but requires a continuous exposure to the disinfectant to effective inactivation . Polymers have the capacity to release viricidal chemicals in a sustained fashion for prolonged periods of time, and may be used to coat patient care items before their use . Iodine was chosen because of its universal antimicrobial potential; it was incorporated into polyurethane polymers and the effectiveness of the polymer-iodine against HIV-1 3B was assayed . STUDY DESIGN: Iodine was loaded into polyurethane polymers by two different methods: polyurethane-complexing, where the iodine is released through a desorption mechanism, and polyurethane-matrixing, where the iodine is released through a diffusion mechanism . The pharmacokinetics of the iodine release were studied in each case . Twenty-four-well viral culture plates used for HIV-1 3B assays were coated with both types of polyurethane-iodine polymers . Their effectiveness against HIV was assessed by MT4 cell viability and reverse transcriptase assays . RESULTS: The polymer-iodine combination remained stable as long as it was dry: the iodine release started only when the plates came in contact with an aqueous environment . The release from the polyurethane-iodine complex was large and rapid, resulting in inactivation of the HIV-1 3B within 15 to 30 minutes, as determined both by reverse transcriptase and the MT4 cytopathic cell cultures assays . The release from the polyurethane-iodine matrix was slower and had no significant antiviral effect . CONCLUSIONS: The polyurethane polymer provided a sustained release of iodine that effectively inactivated HIV . The coating may be applied at the time of manufacturing to specific hospital and laboratory items that are to come in contact with blood from patient-contaminated fluids . This technology is attractive for decontamination, especially in situations where appropriate and rapid disposal of medical waste is not readily available . Further research is in progress to speed the release of the iodine from the polymer and the subsequent inactivation of the virus.

J Infect Dis, 1996 Sep, 174(3), 631 - 5
Multiple strain colonization and metronidazole resistance in Helicobacter pylori-infected patients: identification from sequential and multiple biopsy specimens; Jorgensen M et al.; Helicobacter pylori strain diversity was investigated in infected persons by collection of multiple biopsies before and after therapy failure . It was demonstrated by random amplification of polymorphic DNA polymerase chain reaction that patients may be infected with a mixed population of H . pylori strains . Most patients were colonized with a predominant strain accompanied by up to 5 variant strains . The use of antimicrobials resulted in an altered distribution of the strains present, but the predominant strain usually remained . Patients may be infected with a mixed population of metronidazole-sensitive and -resistant strains at one time, with metronidazole-based therapy selectively enriching for a resistant population.

Curr Microbiol, 1996 Sep, 33(3), 167 - 75
In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages; Rastogi N et al.; Minimal inhibitory concentrations (MICs) of 14 first and second-line antituberculous drugs against drug-susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis (including the multiple drug-resistant or MDR-TB isolates), as well as the type strain H37Rv, were determined radiometrically by the Bactec 460-TB methodols . MICs (microg/ml) of all the fourteen drugs were within an extremely narrow range in case of susceptible strains; isoniazid (0 . 02-0.04), rifampin (0.2-0.4), ethambutol and streptomycin (0.5-2.0), ethionamide (0.25-0.5), D-cycloserine (25-75), capreomycin (1-2), kanamycin (2-4), amikacin (0.5-1.0), clofazimine (0.1-0.4), ofloxacin (0.5-1.0), ciprofloxacin (0.25-1.0), and sparfloxacin (0.1-0.4) . The activity of second-line drugs remained unaltered against MDR-TB isolates resistant to routine first-line drugs . With peak serum level concentrations (Cmax), the intracellular killing of the virulent H37Rv strain was studied in detail in cultured human macrophages . Based on an decreasing order of bactericidal activity, our results showed the following spectrum of intracellular drug action: among the first-line drugs, rifampin > ethionamide = isoniazid > ethambutol > streptomycin > D-cycloserine; among second-line drugs, clofazimine = amikacin > kanamycin = capreomycin; among fluoroquinolones, sparfloxacin > ofloxacin > ciprofloxacin . On the other hand, contrary to atypical mycobacteria, the macrolide drug clarithromycin was inactive against both extracellular and intracellular M . tuberculosis.

BMJ, 1996 Aug 17, 313(7054), 387 - 91
Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study; Arason VA et al.; OBJECTIVE: To study the correlation of antimicrobial consumption with the carriage rate of penicillin resistant and multiresistant pneumococci in children . DESIGN: Cross sectional and analytical prevalence study . SETTING: Five different communities in Iceland . MAIN OUTCOME MEASURE: Prevalence of nasopharyngeal carriage of penicillin resistant pneumococci in children aged under 7 years in relation to antibiotic use as determined by information from parents, patient's records, and total sales of antimicrobials from local pharmacies in four study areas . RESULTS: Total antimicrobial sales for children (6223 prescriptions) among the four areas for which data were available ranged from 9.6 to 23.2 defined daily doses per 1000 children daily (1.1 to 2.6 courses yearly per child) . Children under 2 consumed twice as much as 2-6 year olds (20.5 v 10.9 defined daily doses per 1000 children daily) . Nasopharyngeal specimens were obtained from 919 children, representing 15-38% of the peer population groups in the different areas . Pneumococci were carried by 484 (52.7%) of the children, 47 (9.7%) of the isolates being resistant to penicillin or multiresistant . By multivariate analysis age (< 2 years), area (highest antimicrobial consumption), and individual use of antimicrobials significantly influenced the odds of carrying penicillin resistant pneumococci . By univariate analysis, recent antimicrobial use (two to seven weeks) and use of co-trimoxazole were also significantly associated with carriage of penicillin resistant pneumococci . CONCLUSIONS: Antimicrobial use, with regard to both individual use and total antimicrobial consumption in the community, is strongly associated with nasopharyngeal carriage of penicillin resistant pneumococci in children . Control measures to reduce the prevalence of penicillin resistant pneumococci should include reducing the use of antimicrobials in community health care.

J Mol Biol, 1996 Aug 16, 261(2), 173 - 80
The C-terminal SH3 domain of p67phox binds its natural ligand in a reverse orientation; Finan P et al.; Src-homology 3 (SH3) domains are small protein modules that bind to proline-rich motifs and mediate the formation of signalling complexes . SH3 domains have been implicated in the assembly of the phagocyte NADPH oxidase complex, a multicomponent enzyme responsible for the production of antimicrobial oxidants . Two components of the NADPH oxidase, p67phox and p47phox, each contain two SH3 domains and we have previously shown that the SH3 domain near the carboxyl terminus of p67phox interacts with a proline-rich region of p47phox . In order to gain an insight into the specificity of this interaction, a structural model of the p67phox SH3 domain has been produced using the known structure of the c-abl SH3 domain as a template . The model suggests that the proline-rich ligand of p47phox can bind to the SH3 domain in either of two orientations . In each orientation, the key residues of the SH3 domain that contact the ligand have been identified and altered by site-directed mutagenesis . The ability of the mutated SH3 domains to associate with p47phox from cell lysates was tested and the results provide the first evidence for the binding of a full-length protein to an SH3 domain in a reversed orientation.

J Biol Chem, 1996 Aug 9, 271(32), 19298 - 303
Mode of action of the antimicrobial peptide indolicidin; Falla TJ et al.; Indolicidin is a cationic antimicrobial peptide isolated from bovine neutrophils . It consists of only 13 amino acids, has the highest tryptophan content of any known protein, and is amidated at the carboxyl terminus in nature . By circular dichroism spectroscopy a weak poly-L-proline II extended helix structure was observed that became substantially more pronounced upon interaction with liposomes . Indolicidin bound purified surface lipopolysaccharide with high affinity and permeabilized the outer membrane of Escherichia coli to the small hydrophobic molecule 1-N-phenylnapthylamine (Mr 200), results consistent with indolicidin crossing the outer membrane via the self-promoted uptake pathway . The methyl esterification of indolicidin's carboxyl terminus increased its activity for Gram-negative and Gram-positive bacteria . In Gram-negative bacteria this was associated with an increased binding to lipopolysaccharide and increased permeabilization of the outer membrane . The cytoplasmic membrane was the site of action of indolicidin as assayed in E . coli by the unmasking of cytoplasmic beta-galactosidase due to membrane permeabilization . The mechanism for this activity was shown to be the ability of the peptide to cause an increase in the transmembrane current of planar lipid bilayers . This current increase was activated by transmembrane potentials in excess of -70 to -80 mV . Consistent with this, there was a substantial decrease in indolicidin-mediated bacterial killing and permeabilization of the cytoplasmic membrane of E . coli that had been pretreated with the uncoupler carbonyl cyanide-m-chlorophenyl hydrazone . In planar bilayers, indolicidin induced the formation of discrete channels, which ranged in conductance from 0.05-0.15 nS . Thus despite the small size and unique composition of indolicidin, it was capable of killing Gram-negative bacteria by crossing the outer membrane and causing disruption of the cytoplasmic membrane by channel formation.

FEBS Lett, 1996 Aug 5, 391(1-2), 5 - 8
A novel murine cathelin-like protein expressed in bone marrow; Popsueva AE et al.; A novel cDNA encoding a putative secreted protein was isolated from murine bone marrow . The encoded protein named MCLP (murine cathelin-like protein) was found to be highly homologous to the pig cathelin, and to four neutrophil antimicrobial polypeptides: CAP 18, indolicidin, Bac 5 and FALL-39 . Secondary structure prediction studies identified a highly cationic region in the C-terminal part of prepro-MCLP with a tendency to adopt an amphipathic alpha-helical conformation, as observed in many antimicrobial peptides . However, no antibacterial activity was observed with the synthetic peptide corresponding to this region of MCLP.

Br J Hosp Med, 1996 Aug 21-Sep 3, 56(4), 145 - 50
Antimicrobial therapy: toward the future; Ellis R et al.; The relatively unsophisticated approaches at the beginnings of antimicrobial therapy development, although important at the time, have been replaced by ever more complex and ingenious methods as the medical profession and the pharmaceutical industries face up to the realities of the emerging problems of antimicrobial resistance.

Endod Dent Traumatol, 1996 Aug, 12(4), 179 - 84
Assessment of antibacterial activity of endodontic sealers by a direct contact test; Weiss EI et al.; It is recognized that endodontic success depends on bacterial elimination from the root and root canal system . Antibacterial activity of endodontic sealers can improve the success rate of endodontic treatment, provided the physical properties are not compromised . The aim of this study was to evaluate the antimicrobial properties of two endodontic sealers (AH26 and Endoflas) using a direct contact test (DCT) which was designed for this purpose . The DCT is based on measuring the effect of close contact between test bacteria and the tested material on the kinetics of bacterial outgrowth using a temperature controlled microplate spectrophotometer (THERMOmax) . For comparison, the agar diffusion test (ADT) was performed for both materials . The results of the DCT showed that Endoflas was a significantly more potent bacterial growth inhibitor than AH26, whereas when assessed with the ADT, AH26 was capable of producing a larger inhibition zone than Endoflas . The DCT, by being quantitative and virtually independent of solubility and diffusion, was found more suitable to assay solid surfaces . The results demonstrated the added value of DCT in the study of the antimicrobial properties of endodontic sealers.

Diagn Microbiol Infect Dis, 1996 Aug, 25(4), 191 - 4
Highlights of the French Antimicrobial Resistance Surveillance Project . French Study Group; Pean Y et al.; Thirty-three French laboratories took part in a study to determine the frequency of antibiotic resistance to S . pneumoniae, H . influenzae and M . catarrhalis in different regions of the country . A total of 1317 bacterial isolates were studied . The level of resistance to penicillin among isolates of S . pneumoniae was high particularly in children with otitis media or upper respiratory tract infections . In H . influenzae isolates the level of beta-lactamase production was over 30% in all groups of patients and specimen types and in M . catarrhalis the level of beta-lactamase production was in excess of 90% . Multidrug resistance was found often among the macrolides, tetracyclines, and trimethoprim/sulfamethoxazole, and these antimicrobials should not be regarded as therapeutic alternatives to the beta-lactams.

Diagn Microbiol Infect Dis, 1996 Aug, 25(4), 162 - 8
WHONET: removing obstacles to the full use of information about antimicrobial resistance; O'Brien TF et al.; A rich store of detailed information about antimicrobial resistance is at each medical center in paper files inaccessible to analysis or in electronic files too diverse to support a common analytical software . WHONET puts that information on a personal computer at each center in a file code and format that is the same at all centers, so that one software can then fully analyze the files at any center or those merged from many centers . The software monitors the complex matrix of interrelationships between all the measurements of resistance to antimicrobials of tested isolates of each species and of control strains . Differences at a center over time or between centers reflect differences in test performance or in the prevalence of specific resistant strains, which may be tracked . The software helps workers who are knowledgeable about resistance, infection control and clinical use of antimicrobials at any center to control test quality and integrate the management of resistance there . Their ongoing monitoring and experience locally also builds the quality and interpretation of the files merged from many centers.

Diagn Microbiol Infect Dis, 1996 Aug, 25(4), 153 - 61
The emergent needs for basic research, education, and surveillance of antimicrobial resistance . Problems facing the report from the American Society for Microbiology Task Force on Antibiotic Resistance; Jones RN; The American Society for Microbiology (ASM) convened a task force to study the current prevelance of antibiotic resistance and the problems associated with it . The task force produced a series of recommendations centered around three key elements: (a) education of the physician and the public; (b) encouragement of more basic research directed to the development of new antimicrobials and vaccines; and (c) the setting-up of a national surveillance system to both confirm and monitor the extent of the problem . Since the publication of this report in 1995, progress has been slow . No "consortium-style" funding has been set aside and any initiatives, such as the first steps in an education program by the ASM, are still in their planning phases . The spirit of cooperation and trust needed to deal with this problem appears to be lacking.

Farmaco, 1996 Aug-Sep, 51(8-9), 613 - 5
Synthesis, antimicrobial and cytostatic activity of 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranosyl (-)-(S)-propanesulfinate; Saenz MT et al.; The synthesis of 1,2:5,6-di-O-isopropilidene-alpha-D-glucofuranosyl (-)-(S)-propanesulfinate 1 optically pure using diacetone-D-glucose as unique inducer of chirality and iPrEtN a base is described . Compound 1 was especially active against Gram positive bacteria . For the cytostatic activity, the ID50 value of compound 1 was inferior than those recommend by National Cancer Institute of USA for this type of compounds.

J Dent Res, 1996 Aug, 75(8), 1578 - 84
Hydrolysis of triclosan monophosphate by dental plaque and selected species of oral micro-organisms; Greenman J et al.; Triclosan monophosphate is a phosphorylated derivative of the antimicrobial agent, triclosan . In comparison with triclosan, it is highly soluble in aqueous solutions . It is hypothesized that, within the oral environment, triclosan monophosphate (which may be devoid of antimicrobial activity) will be hydrolyzed into triclosan by the action of microbial phosphatases . The liberated triclosan may then exert antimicrobial activity . To test this hypothesis, we designed experiments to measure the phosphatase activity of plaque and selected species of oral micro-organisms and to demonstrate hydrolysis of triclosan monophosphate . Tests comparing the minimal inhibitory concentration and minimal bactericidal concentration of triclosan and triclosan monophosphate were also undertaken . Dental plaque and the majority of the bacterial strains tested showed phosphatase activity against p-nitrophenyl phosphate which peaked below neutral pH (acid phosphatases) or above neutral pH (alkaline phosphatases) . Dental plaque showed the highest levels of alkaline phosphatase (optimum at pH 9.0) and relatively high levels of acid phosphatase (optimum at pH 6.0 to 6.5) . Dental plaque and selected species of micro-organisms were all capable of hydrolyzing triclosan monophosphate, albeit at different rates . The minimal inhibitory concentration and minimal bactericidal concentration values for triclosan monophosphate against eight bacterial strains were always considerably higher than the corresponding values for triclosan . Addition of triclosan monophosphate to an established culture (ca . 10(9) cfu/mL) of Capnocytophaga gingivalis growing continuously showed that triclosan monophosphate was rapidly hydrolyzed into triclosan with concomitant loss of total bacterial viability . It is therefore likely that triclosan monophosphate will be broken down into triclosan within the oral environment with concomitant antimicrobial activity.

Intern Med, 1996 Aug, 35(8), 629 - 36
Predicting infection in hospitalized patients with systemic lupus erythematosus; Yuhara T et al.; To identify the risk factors for infection and to develop a model for the prediction of infection in hospitalized patients with active systemic lupus erythematosus (SLE), we carried out a retrospective cohort study with clinical data collected from 121 consecutive patients with active SLE . Seventeen patients had infection within 6 months of beginning steroid therapy for active SLE . Independent multivariate predictors of infection were a decrease in the serum albumin value, an increase in the serum creatinine value, and prednisolone use in a dose of > or = 60 mg/day without methylprednisolone pulse therapy . The error rate of the model by 10-fold cross-validation method was 12%, sensitivity was 65%, specificity was 91%, and positive predictive value was 55% . Four nonsurvivors were correctly discriminated . Use of this model could contribute to earlier diagnosis of infection and may assist decisions regarding empiric antimicrobial administration in patients with SLE.

J Vet Med Sci, 1996 Aug, 58(8), 783 - 5
Effect of a combination of antimicrobial agents for the treatment of respiratory disease in cattle; Katoh T et al.; Clinical effect of the administration of thiamphenicol (TP) and tylosin (TS) on bovine respiratory disease was investigated . Group I (n = 64) were administered TP (10 mg/kg) and TS (4 mg/kg), group II (n = 26) were given TP (5 mg/kg) and TS (2 mg/kg) . For the control, TP group (n = 25) were given 20 mg/kg of TP and ampicillin group (n = 23) were given 10 mg/kg of ampicillin . As a result, improvement of clinical findings was more rapid and the cure rate was significantly higher in group I compared to those in the other 3 groups . These results showed that a combination therapy with minimal basic doses of TP and TS is very effective for some respiratory diseases in cattle.

J Vet Med Sci, 1996 Aug, 58(8), 755 - 9
Influence of calcium concentration on the antimicrobial activity of lasalocid against Selenomonas ruminantium; Nakamura I et al.; The present study was designed to examine the interaction between the effects of lasalocid and Ca2+ on the growth and structure of Selenomonas ruminantium HD-4 . Lasalocid, at a dose of 10 microM, inhibited cell growth almost completely after 12 hr incubation in the presence of relatively high extracellular concentrations of Ca2+ (from 5 to 50 mM), but only slightly reduced cell growth in the presence of 0.2 mM Ca2+ . With Ca2+ alone, cell growth was also inhibited at 12 hr as a function of the concentration of Ca2+ over the range 5 to 50 mM . In cultures at mid-exponential phase, growth was markedly inhibited by the simultaneous addition of 10 microM lasalocid and 15 mM Ca2+, but only moderately inhibited by lasalocid in the absence of Ca2+ . However, there was no significant effect on bacterial growth at the mid-exponential phase when Ca2+ alone was added to the incubation medium . In thin sections of cells treated with lasalocid in the presence of 15 mM Ca2+, abnormal cells were found with cytoplasmic voids and with an outer membrane detached from the inner membrane layer, this change in the outer membrane was also found in cells treated with lasalocid alone . There was no visible abnormality in the outer membrane in thin sections of Ca2(+)-treated cells, while most of these cells showed only a slight contraction of cytoplasmic material or a loss of cytoplasmic contents . These results indicate the presence of a synergistic effect between the actions of lasalocid and Ca2+ on cell growth, presumably due to induced cytoplasmic alterations.

J Antimicrob Chemother, 1996 Aug, 38(2), 309 - 14
The influence of the opinion of an infectious disease consultant on the appropriateness of antibiotic treatment in a general hospital; Gomez J et al.; The antibiotics chosen in hospitals are not always the most appropriate . A comparative prospective study with sequential analysis was designed to assess how the opinion of an infectious disease consultant affected the clinical efficacy of antimicrobial treatment in a general hospital . We studied 250 patients who had microbiologically documented infections according to Center for Disease Control criteria . The patients were divided in two groups with similar initial characteristics . Group G1 comprised 100 patients without infectious disease consultation, and group G2 contained 150 patients with infectious disease consultation . The influence of the consultant's opinion was assessed as the percentage of initially appropriate treatments, and by the number of inappropriate ones that were changed after the microbiological results were known . The appropriateness of initial treatment was significantly higher in group G2 (66% vs 55%), as were the number of treatments changed on the basis of the microbiological results (57.6% vs 33.3%) . This lead to higher rates of cure, fewer deaths, and fewer cases of persistent infection in group G2 . In 42.4% of G2 patients, antibiotic treatment was not changed in spite of the microbiological results and the opinion of an infectious disease consultant . We conclude that antibiotic treatment for the most clinically significant infections can be optimized if it is dispensed according to carefully developed guidelines.

J Antimicrob Chemother, 1996 Aug, 38(2), 301 - 8
Optimizing the timing of antimicrobial prophylaxis in surgery: an intervention study; Gyssens IC et al.; The timing of surgical antimicrobial prophylaxis was determined before and after an intervention programme of education of surgeons, anaesthetists and nurses on the subject of antimicrobial drug prophylaxis, and the subsequent implementation of new protocols of single dose prophylaxis administered within one hour before incision . This prospective study was performed in three surgical departments of a university hospital . For comparison, the timing of prophylaxis was also determined in an operating department of a community hospital . The timing improved considerably in the departments of the university hospital where the intervention was carried out: administration of the first dose within one hour before incision increased from 39% to 69% in department A and from 64% to 80% in department B . Before the intervention, seven out of 16 prophylactic doses were given after inflation of the tourniquet . After the intervention all doses of prophylactic antibiotics were administered before inflation of the tourniquet . Initially, the intervals of multidose prophylaxis varied widely . In the second review, single-dose prophylaxis increased from 21% to 78% in department A and from 31% to 85% in department B . We conclude that the intervention succeeded in improving the quality of surgical prophylaxis.

J Antimicrob Chemother, 1996 Aug, 38(2), 193 - 203
A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone; MacGowan AP et al.; A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve . From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined . The area-under-the-curve (AUC) was calculated from the theoretical curve . The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate . In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics . The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

Infect Control Hosp Epidemiol, 1996 Aug, 17(8), 490 - 5
Preventing the emergence of multidrug-resistant microorganisms through antimicrobial use controls: the complexity of the problem; Jarvis WR; Widespread use of antimicrobials in the inpatient and outpatient setting has been associated with the emergence of multidrug-resistant microorganisms . A variety of methods exist to improve the appropriateness of antimicrobial use in the inpatient setting, including guidelines, antimicrobial use evaluations, micribiology laboratory guidance, formulary development and antimicrobial restriction, use of antimicrobial order or automatic stop order forms, and antimicrobial audits . To decrease the selective pressure that leads to development of pathogen resistance and to reduce antimicrobial expenditures, infectious disease, infection control, pharmacy, and administrative staff need to improve clinician use of antimicrobials through development and implementation of antimicrobial use committees . Through the implementation of a comprehensive, multidisciplinary approach to antimicrobial use and development of clinician education programs, inappropriate antimicrobial use can be reduced, patient care can be improved, and substantial cost savings can be realized.

Infect Control Hosp Epidemiol, 1996 Aug, 17(8), 484 - 9
Emerging infectious diseases in the institutional setting: another hot zone; Ostroff SM; During the closing years of the 20th century, there has been an unprecedented number of newly recognized infectious agents and a resurgence of infectious diseases only recently thought to be conquered . These problems have been compounded by the increasing number of pathogens that have evolved resistance to antimicrobial agents . Hospitals and other institutional settings occupy a pivotal niche in the emergence of infectious agents due to factors such as the large concentrations of ill and immuno-compromised persons, evolving technologies in healthcare settings, routine breeches of host defense mechanisms, and frequent use of antimicrobial agents . Any comprehensive strategy to address emerging infectious diseases must incorporate provisions for healthcare settings, including efforts to enhance surveillance, response capacity, training, education, applied research, and routine implementation of prevention measures.

J Chemother, 1996 Aug, 8(4), 284 - 9
Efficacy of sulbactam-ampicillin for the treatment of severe diabetic foot infections; Akova M et al.; Diabetic foot infections, a frequent and serious cause of morbidity in patients with diabetes mellitus, are caused by anaerobic and aerobic bacteria . Given the fact that seriously impaired host defense factors are almost always present in these patients, bactericidal agents with a broad spectrum of antimicrobial activity are required for their treatment . Seventy-four patients with diabetic foot infections were treated with parenteral sulbactam-ampicillin (1.5 g, q.i.d.) . All patients were followed-up prospectively in order to determine the efficacy and safety of sulbactam-ampicillin . The mean duration (+/- SD) of treatment in patients with osteomyelitis (n = 49) and soft tissue infections (n = 25) was 41 +/- 5 and 14 +/- 3 days, respectively . Infected limbs were amputated at various levels in 14 patients (19%) . Clinical cure rates were 86% and 100% in patients with osteomyelitis and with soft tissue infection, respectively . The most frequent side effect was diarrhea and observed in 10 patients (14%) . The results of the present study indicate that sulbactam-ampicillin is safe and effective in the treatment of diabetic foot infections.

J Chemother, 1996 Aug, 8(4), 270 - 7
Greek physicians' and dentists' compliance with the British society for antimicrobial chemotherapy (BSAC) guidelines for preventing bacterial endocarditis; Panos G et al.; Two thousand questionnaires inquiring about applied prophylaxis for bacterial endocarditis were sent to practicing doctors in Greece . Two hundred and ninety-nine questionnaires were completed and returned (15% response rate) and were subsequently divided into two groups: Group A (163) consisting of responses from dentists, chest physicians and ear, nose and throat (ENT) specialists and group B (136) including responses from gastroenterologists, gynecologists, urologists and radiologists . The percentage of correct answers given in response by clinicians in Groups A and B to the main questions and in accordance with the 1992 guidelines of the British Society for Antimicrobial Chemotherapy (BSAC) were respectively: (a) 53% vs 35% asked patients their previous history pertaining to valve disease, rheumatic fever or prosthetic valve surgery; (b) 55% vs 33% administered prophylaxis to patients with relevant history prior to medical procedures; (c) 67% vs 0% of prescribing doctors administered the appropriate antibacterials; (d) 33% vs 31% initiated prophylaxis in proper timing prior to medical procedure; (e) 14% vs 13% administered antibiotics in correct time/route/duration of infusion where applicable, prior to medical procedure; (f) 7% of group A doctors administering recommended antibiotics, implemented prophylaxis with correct time/route/dosage while, although none of group B doctors administered recommended antibiotics, 7% implemented prophylaxis with correct time/route recommendations; (g) an overall 2% of doctors from both groups met the BSAC recommendations . In conclusion, it is imperative that the appropriate training of doctors in all subspecialties regarding prophylaxis of bacterial endocarditis and according to current recommendations be carried out.

Pharm World Sci, 1996 Aug, 18(4), 137 - 41
Feasibility of an antibiotic order form . First experience in the department of internal medicine of a university hospital; Blok WL et al.; Inadequate control of antimicrobial drug use may lead to excessive expenditure for antimicrobial drugs and improper prescribing it may also result in the emergence of multiresistant bacteria . An antibiotic order form may improve the quality of prescriptions by increasing the awareness of the physician of the antimicrobial spectrum needed (i.e . which microorganism is expected in a given patient), the desired duration of treatment, the potential need to adjust dosage, and the potential allergy of the patient to the drug . Furthermore, such an antibiotic order form facilitates prospective evaluation of both the quantity and the quality of prescribing practice . However, the introduction of yet another form to fill in may be met with opposition from prescribers . We have developed an easy-to-use antibiotic order form that incorporated the conventional medication order that was already in use in our hospital . Compliance (percentage of antimicrobial drug prescriptions for which an order form was used) was on average 58% in the first two weeks after introduction, and remained thereafter between 60% and 90%, varying between the different wards . Data retrieved from the antibiotic order forms could be used for surveillance We conclude that this antibiotic order form was feasible in a large department of internal medicine of a university hospital . Future usefulness will depend on compliance and on personnel support for data processing and intervention.

Inflamm Res, 1996 Aug, 45(8), 376 - 9
Interaction between enoxacin, a new antimicrobial, and nimesulide, a new non-steroidal anti-inflammatory agent in mice; Taniguchi Y et al.; Convulsions induced by the combination of enoxacin, a new antimicrobial, and nonsteroidal anti-inflammatory drugs including nimesulide, ketoprofen, pranoprofen and loxoprofen sodium, were investigated in mice . The oral administration of nimesulide alone induced clonic convulsions at more than 300 mg/kg . The oral administration of ketoprofen, pranoprofen or loxoprofen sodium induced no convulsion up to 1000 mg/kg, 500 mg/kg and 600 mg/kg, respectively, and that of enoxacin induced no convulsion at more than 5000 mg/kg . The combination of nimesulide at 200 mg/kg and enoxacin at 400 mg/kg induced no convulsion . In contrast, the combination of enoxacin at 100 mg/kg and either ketoprofen at 125 mg/kg or pranoprofen at 500 mg/kg induced clonic convulsions, while that of enoxacin at 400 mg/kg and loxoprofen sodium at 600 mg/kg induced no convulsion . These results suggest that the combination of nimesulide and enoxacin may possibly induce few or less convulsions in the clinical setting.

J Pharm Sci, 1996 Aug, 85(8), 803 - 9
Interaction of norfloxacin with divalent and trivalent pharmaceutical cations . In vitro complexation and in vivo pharmacokinetic studies in the dog; Wallis SC et al.; The formation constants of the fluoroquinolones norfloxacin and ciprofloxacin with Mg2+ (log beta 1 = 2.97(4), log beta 2 = 5.6(2)), Zn2+ (log beta 1 = 3.77(2), log beta 2 = 7.59(3)), and Fe2+ (log beta 1 = 3.99(5), log beta 2 = 7.2(5)) were determined by potentiometric titration . The pH at which precipitation occurred in the titration solutions was compared for the metal ions Ca2+, Mg2+, Zn2+, Fe2+, Cu2+, and Al3+ . The formation constants were used to predict a rank order of metals that may be expected to hinder the gastrointestinal absorption of the fluoroquinolones, in vivo . The effects of metal ions on the pharmacokinetics of orally-administered norfloxacin in the dog were investigated . Norfloxacin (12 mg/kg) was administered alone or with equimolar doses of each of the chloride salts of Ca2+, Mg2+, Zn2+, Fe2+, and Al3+ . Statistically significant reductions in serum norfloxacin concentrations were observed after analysis by HPLC . The Cmax was reduced 29-85%, while the area under the norfloxacin serum concentration-time curve (AUC0-infinity) was reduced by 29-79% . The extent of the reduction in AUC0-infinity was correlated with the magnitude of the formation constant of the 1:1 norfloxacin:metal chelate complex for the divalent metal ions . On coadministration of 12 mg/kg norfloxacin with various doses of Mg2+ (chloride) the AUC0-infinity and Cmax decreased with increasing Mg2+ dose . The interaction peaked at a Mg2+:norfloxacin ratio of 1:2 suggesting the formation of a 1:2 Mg:norfloxacin complex . Formation constant data were used to simulate the percentage of norfloxacin complexed at pH 6.5 . Combinations of metal ion and norfloxacin which result in only a small extent (< 20%) of norfloxacin complex formation can result in relatively large decreases in oral bioavailability of this antimicrobial agent.

J Otolaryngol, 1996 Aug, 25(4), 227 - 33
Deep-neck space abscesses; el-Sayed Y et al.; OBJECTIVE: Despite a reduction in the incidence, deep-neck space infections are still seen today with definite potential for significant morbidity and even mortality . DESIGN: The authors present their experience in the management of 16 patients with 19 deep-neck space abscesses . The distribution of the abscesses were: 5 Ludwig's angina, 4 parapharyngeal abscesses, 3 retropharyngeal abscesses, 3 in the sub-mandibular triangle, 3 in the deep anterior triangle, and 1 in the deep posterior triangle . RESULTS: The source of infection was odontogenic in six patients, pharyngeal in three, otogenic in one, and could not be identified in the other six patients . Most cases presented with pain and neck swelling . Plain x-ray films, computed tomography, ultrasonography, and magnetic resonance imaging were the main diagnostic procedures . Positive culture was obtained in only nine cases (56.2%) . No predominant single organism was identified . Antimicrobial therapy and surgical drainage were the mainstay of treatment . Two cases were complicated by internal jugular-vein thrombophlebitis . All the patients survived without major residual sequelae . CONCLUSIONS: The etiology, presentation, and management of deep-neck space infections are briefly reviewed.

Semin Oncol Nurs, 1996 Aug, 12(3), 193 - 201
Home infusion therapy; Gorski LA et al.; OBJECTIVES: To examine issues related to the planning of an effective home infusion therapy program and to provide an overview of specific home infusion therapies for patients with cancer . DATA SOURCES: Published articles, research studies, guidelines, and standards pertaining to infusion therapies . CONCLUSIONS: Advances in technology have expanded and increased the scope and success of home infusion therapy . Antimicrobial therapy, chemotherapy, pain management, total parenteral nutrition, and blood transfusion therapy are commonly administered to cancer patients at home . IMPLICATIONS FOR NURSING PRACTICE: A competent and experienced nursing staff is the cornerstone of a successful home infusion program . Safe provision of infusion therapy and care can be assured through selection of appropriate patients, effective patient education, well-defined agency policies, and effective coordination of home care services.

Vet Clin North Am Equine Pract, 1996 Aug, 12(2), 303 - 35
Instrumentation and techniques for treating orthopedic infections in horses; Baxter GM; Orthopedic infections-those involving bones, joints, tendon sheaths, or bursae-are some of the most difficult problems for equine surgeons to treat successfully . Sources of the infection are usually hematogenous, traumatic, or iatrogenic and knowledge of the most likely causative bacteria is very useful in selecting the most appropriate antimicrobial(s) to either prevent or treat these infections in horses . This article discusses the clinical findings, diagnosis, treatment, and prevention of orthopedic infections in horses . More recent treatment methods such as synovial drainage techniques (arthroscopy and arthrotomy), intrasynovial antimicrobials, regional perfusion of antimicrobials, and antimicrobial-impregnated polymethylmethacrylate (PMMA) beads or cylinders are also addressed.

Vet Clin North Am Equine Pract, 1996 Aug, 12(2), 173 - 94
Instrument sterilization, skin preparation, and wound management; Southwood LL et al.; Recent advances in instrument sterilization include the introduction of gas plasma sterilization and the increased use of glutaraldehyde . Gas plasma sterilization has the advantages of no toxic residue effects, reduced turnover time, and applicability for sterilization of heat- and moisture-sensitive instruments . Chlorhexidine gluconate (4%) appears to be a superior preoperative surgical scrub for both the surgeon and the patient because of its increased antimicrobial efficacy, residual activity, and minimal tissue reactions . There are many new wound dressings and topical medications for treatment of wounds, but the efficacy of most of these preparations has been evaluated only in humans, dogs, and cats . The ideal topical wound preparation and dressing for equine wounds, particularly wounds affecting the distal limb, have not yet been found.

New Horiz, 1996 Aug, 4(3), 377 - 84
Efforts of pharmacy to reduce antibiotic resistance; Klem C et al.; Pharmacists have an integral role in the care of ICU patients, including those with infections . Antibiotics continue to be among the most widely prescribed drugs in the ICU environment . This article focuses on the impact pharmacists have on the care and economics for the critically ill infected patient and on mechanisms used in hospitals to control antibiotic misuse . Numerous studies point to inappropriate antibiotic use and resultant selection pressure on antimicrobial resistance . The critical care pharmacist can impact this prescribing by assuring optimal pharmacotherapy specific for the organism and associated disease . Furthermore, policies have been implemented to modify antibiotic use, including formulary manipulations, antibiotic stop order forms, care plans, antibiotic cycling, oral switching, and computer-assisted antimicrobial therapy . Future research is needed to determine the optimal method for preventing resistance . However, a multidisciplinary approach to rational antimicrobial use is suggested.

New Horiz, 1996 Aug, 4(3), 370 - 6
Does antibiotic restriction prevent resistance?
McGowan JE Jr, Gerding DN.
Antimicrobial resistance among some hospital organisms has increased to a stage where it can no longer be tolerated . The need for preventive and corrective measures is urgent . There is an association between the use of antimicrobial agents and resistance that is likely causal . Alterations in antimicrobial usage have been shown to affect antimicrobial resistance rates, particularly with use of aminoglycosides . Efforts to improve antimicrobial use through educational efforts alone have been largely ineffective, even when coupled with quality management or clinical guideline aspects . Thus, further work is urgently needed to determine the impact of antimicrobial-use controls . Additional large-scale, well controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular biological organism typing, and precise resistance mechanism analysis will be required to determine the best methods to prevent and control this problem and ensure our optimal antimicrobial-use "stewardship." Consideration of the long-term effects of antimicrobial selection, dosage, and duration of treatment on resistance development should be a part of every antimicrobial treatment decision.

New Horiz, 1996 Aug, 4(3), 361 - 9
Role of the microbiology laboratory in monitoring and identifying resistance: use of molecular biology; Pfaller MA et al.; Antimicrobial resistance is an increasing problem in the United States . Early detection of emerging trends in antimicrobial resistance may facilitate implementation of effective control measures . Most antimicrobial susceptibility testing is qualitative, in that it categorizes isolates as susceptible, intermediate, or resistant . This approach is relatively inexpensive and generally adequate for clinical purposes . Qualitative susceptibility testing has some limitations for monitoring for emerging resistance . Selective quantitative susceptibility testing may be useful in detecting early trends toward elevated minimal inhibitory concentrations . Molecular methods have a role also in characterizing mechanisms of resistance and in the typing of resistant strains to determine patterns of spread . Laboratory monitoring of emerging resistance must be associated with an effective infection control policy and a willingness to modify practice in a rational manner based upon the trends detected.

Nephrol Dial Transplant, 1996 Aug, 11(8), 1582 - 5
Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration; Joos B et al.; BACKGROUND: The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task . More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments . METHODS: Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin, flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH) . Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay . Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations . Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance . RESULTS: A total of 37 treatment periods was studied . Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3.2-22.1) ml/min . Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained . CONCLUSIONS: Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known . The individual dosage requirements may be calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in the absence of renal impairment.

Clin Pharmacokinet, 1996 Aug, 31(2), 156 - 63
Pharmacokinetic optimisation of the treatment of septic arthritis; Hamed KA et al.; Early diagnosis and treatment of septic arthritis improves the potential for a favourable outcome . Optimal treatment includes the prompt and judicious use of effective antimicrobial agents coupled with prompt drainage of the affected joint . Adequate drainage may be accomplished by means of repeated closed large-bore needle aspiration, arthroscopy, or an open surgical procedure . The purpose of this article is to describe optimal antimicrobial therapy based upon available pharmacokinetic data . The host-dependent vulnerability to specific pathogens, local antibacterial susceptibility patterns and knowledge of antibacterial activity at the site of infection must all be taken into account when planning appropriate treatment . This article does not address arthritis secondary to human and animal bites, diabetic foot infections, mycobacteria, fungi, Lyme spirochaete, or other nonbacterial causes of septic arthritis.

Aliment Pharmacol Ther, 1996 Aug, 10(4), 617 - 21
One-week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection; Yousfi MM et al.; BACKGROUND: Multi-drug regimens are generally required to reliably cure H . pylori infection . We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H . pylori infection . OBJECTIVES: To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H . pylori infection . METHODS: We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H . pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture . RESULTS: Thirty-one patients with documented peptic ulcer disease and H . pylori infection were treated . The H . pylori infection was cured in 24 (77%, 95% CI = 58-90%) (intention-to-treat) . In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI = 60-92%) . One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication . Mild side-effects were reported by 16% including diarrhoea, headache and altered taste . Compliance averaged 95% . Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy . CONCLUSION: This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates . Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.

Plant Mol Biol, 1996 Aug, 31(5), 993 - 1008
Antimicrobial peptides from Mirabilis jalapa and Amaranthus caudatus: expression, processing, localization and biological activity in transgenic tobacco; De Bolle MF et al.; The cDNAs encoding the seed antimicrobial peptides (AMPs) from Mirabilis jalapa (Mj-AMP2) and Amaranthus caudatus (Ac-AMP2) have previously been characterized and it was found that Mj-AMP2 and Ac-AMP2 are processed from a precursor preprotein and preproprotein, respectively {De Bolle et al., Plant Mol Biol 28:713-721 (1995) and 22:1187-1190 (1993), respectively} . In order to study the processing, sorting and biological activity of these antimicrobial peptides in transgenic tobacco, four different gene constructs were made: a Mj-AMP2 wild-type gene construct, a Mj-AMP2 mutant gene construct which was extended by a sequence encoding the barley lectin carboxyl-terminal propeptide, a known vacuolar targeting signal {Bednarek and Raikhel, Plant Cell 3: 1195-1206 (1991)}; an Ac-AMP2 wild-type gene construct; and finally, an Ac-AMP2 mutant gene construct which was truncated in order to delete the sequence encoding the genuine carboxyl-terminal propeptide . Processing and localization analysis indicated that an isoform of Ac-AMP2 with a cleaved-off carboxyl-terminal arginine was localized in the intercellular fluid fraction of plants expressing either wild-type or mutant gene constructs . Mj-AMP2 was recovered extracellularly in plants transformed with Mj-AMP2 wild-type gene construct, whereas an Mj-AMP2 isoform with a cleaved-off carboxyl-terminal arginine accumulated intracellularly in plants expressing the mutant precursor protein with the barley lectin propeptide . The in vitro antifungal activity of the AMPs purified from transgenic tobacco expressing any of the four different precursor proteins was similar to that of the authentic proteins . However, none of the transgenic plants showed enhanced resistance against infection with either Botrytis cinerea or Alternaria longipes.

Antimicrob Agents Chemother, 1996 Aug, 40(8), 1875 - 80
Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes; Mizuki Y et al.; Enoxacin, an antimicrobial fluoroquinolone with a 7-piperazinyl-1, 8-naphthyridine skeleton, is a potent inhibitor of cytochrome P-450-mediated theophylline metabolism . The present study was designed to clarify, using seven enoxacin derivatives, the molecular characteristics of the fluoroquinolone responsible for the inhibition . Three derivatives with methyl-substituted 7-piperazine rings inhibited rat liver microsomal theophylline metabolism to 1,3-dimethyluric acid to an extent similar to that of enoxacin (50% inhibitory concentrations {IC50s} = 0.39 to 0.48 mM) . 7-Piperazinyl-quinoline derivatives, 8-hydroenoxacin (8-Hy) and 1-cyclopropyl-8-fluoroenoxacin (8-F1), which have a hydrogen and a fluorine at position 8, respectively, more weakly inhibited metabolite formation (IC50s = 0.88 and 1.29 mM, respectively) . Little inhibition (IC50 > 2 mM) was observed in those with 3'-carbonyl and 4'-N-acetyl groups on the piperazine rings . The substrate-induced difference spectra demonstrated that the affinities of enoxacin, 8-Hy, and 8-F1 to cytochrome P-450 were parallel with their inhibitory activities . The substituent at position 8 was found to determine the molecular conformations of the fluoroquinolones, and the planarity in molecular shape decreased in the same order as the inhibitory activity (enoxacin > 8-Hy > 8-F1) . Moreover, the 3'-carbonyl and 4'-N-acetyl groups decreased the basicity of their vicinal 4'-nitrogen atoms when judged from their electrostatic potentials, which showed a remarkably broadened negative charge around the nitrogens . As a result, the planarity of the whole molecule and the basicity of the 4'-nitrogen atom of enoxacin are likely to be dominant factors in the inhibition of theophylline metabolism by cytochrome P-450.

Clin Infect Dis, 1996 Aug, 23(2), 341 - 68
Managed care and the infectious diseases specialist; Tice AD et al.; There is growing demand to contain health care costs and to reassess the value of medical services . The traditional hospital, academic, and research roles of the infectious disease (ID) specialist are threatened, yet there is an increasing need for expertise because of growing antimicrobial resistance and emerging pathogens . Opportunities exist to develop and expand services for the care of patients infected with human immunodeficiency virus and in infection control, epidemiology, outcomes research, outpatient intravenous therapy, and resource management . It is important for ID physicians to appreciate the principles involved in managed care and the areas in which ID services can be valuable . To be effective, physicians need to know about tools such as practice guidelines, physician profiling, outcomes monitoring, computerized information management, risk sharing, networking, and marketing, as well as related legal issues . With a positive attitude toward learning, application, and leadership, ID physicians can redefine their role and expand their services through managed care.

Clin Infect Dis, 1996 Aug, 23(2), 286 - 91
Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation?
Tan JS, Friedman NM, Hazelton-Miller C, Flanagan JP, File TM Jr.
We retrospectively evaluated the charts of 112 patients with diabetic foot infection to determine if early aggressive surgical intervention improves outcome . All patients were classified into two groups on the basis of the timing of surgical intervention and appropriate antimicrobial therapy . Group I included patients who underwent no surgical intervention during the first 3 days of hospitalization but received intravenous antimicrobial therapy, and group II included patients who underwent surgical intervention promptly and received intravenous antimicrobial therapy . Group II was further divided; group IIA included patients who underwent debridement, and group IIB included patients who underwent local limited amputation . A higher rate of patients in group I than in group II (27.6% vs . 13%, respectively; P < .01) required above-ankle amputation during the same hospitalization or subsequent admission . Overall, an aggressive surgical approach against foot infection in hospitalized diabetic patients reduced the need for above-ankle amputation and the length of hospital stay by at least 6 days . Treatment of diabetic foot infection requires the combination of early surgical treatment and antimicrobial therapy.

Kekkaku, 1996 Aug, 71(8), 459 - 64
{In vitro activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis}; Sato K et al.; In vitro antimicrobial activities of the benzoxazinorifamycin derivative KRM-1648 (KRM) against 50 strains of Mycobacterium tuberculosis isolated from patients with mainly intractable pulmonary tuberculosis were studied . MIC90 values of KRM, rifabutin (RBT) and rifampicin (RFP) for RFP-sensitive strains (27 strains; defined as those with MICRFP values of < 1.56 micrograms/ml) were 0.013, 0.1 and 0.4 micrograms/ml, respectively, when determined by the agar dilution method using 7H11 medium . MIC90 values of KRM, RBT, and RFP for RFP-resistant strains (23 strains; defined as those having MICRFP values of > or = 1.56 micrograms/ml) were 100, 12.5 and > 100 micrograms/ml, respectively . MICs of KRM against 50 clinical isolates of M . tuberculosis distributed over a much lower range than those of RFP . KRM showed more potent antimicrobial activity than RBT against the organisms with low MIC values (< or = 1.56 micrograms/ml), while it was not so active as RBT against the organisms with high MIC values (> or = 3.13 micrograms/ml) . Cross-resistance between KRM and RFP or RBT was observed for M . tuberculosis.

Vet Hum Toxicol, 1996 Aug, 38(4), 254 - 9
In vitro and in vivo study of the effects of enrofloxacin on hepatic cytochrome P-450 . Potential for drug interactions; Vancutsem PM et al.; Enrofloxacin (EF; BAYTRIL, Miles) was the first fluoroquinolone antimicrobial to be used in veterinary medicine in the US . In humans, fluoroquinolones hinder the metabolism of other clinically important drugs through inhibition of hepatic cytochrome P-450's (P450) . Similar interactions are suspected in animals . In this study, we characterized the ability of EF to modify the enzymatic activity of the P450 IA and IIB families . In an in vitro experiment, the inhibition of P450 reductase by EF was assessed by measuring the NADPH-cytochrome c reductase activity, and the inhibition of P450IA1, IA2 and IIB by 0.25, 0.5 and 1.0 mM EF was studied, respectively, by measuring the ethoxy (EROD), methoxy (MROD) and pentoxy (PROD) O-dealkylation activities in rat liver microsomes . NADPH-cytochrome c reductase was not affected . Enrofloxacin induced a strong, concentration-dependent inhibition of P450IA1 and IA2 . In an in vivo experiment, the effects of 5 administrations of 5 (EF5), 25 (EF25) or 100 (EF100) mg/kg/d were assessed in rats . The liver cytochrome b5 and total P450 content was assayed by spectrophotometric measurements; P450IA and P450IIB isozyme contents were evaluated by immunoblotting with isozyme specific monoclonal antibodies, and by measuring MROD, EROD and PROD activities . A slight induction of P450IIB1 and IIB2 expression and activity (140% of controls) was only present after EF5 treatment . We concluded that EF directly inhibits P450IA1 and IA2 and advise caution when drugs metabolized extensively by these P450 isozymes are administered in association with EF . The slight stimulation of the P450IIB subfamily is not a concern at the recommended therapeutic dose of 5 mg EF/kg.

J Clin Microbiol, 1996 Aug, 34(8), 1980 - 4
Comparison of efficacy and cost-effectiveness of BIOMIC VIDEO and Vitek antimicrobial susceptibility test systems for use in the clinical microbiology laboratory; Berke I et al.; Antimicrobial susceptibility testing expense may be a significant portion of a clinical microbiology laboratory's budget . This study compares the BIOMIC VIDEO system (Giles Scientific, Inc., New York, N.Y.) with the Vitek system (bioMerieux Vitek, Inc., Hazelwood, Mo.), an established automated method of antimicrobial susceptibility testing with the ability to generate MIC data . The BIOMIC system is relatively inexpensive and automates the reading of the classical disk agar diffusion test to provide both qualitative (susceptibility interpretation) and quantitative (MIC) data . The overall MIC correlation between the two systems for the 2,913 drug-organism combinations tested was 92.6% . The overall agreement for susceptibility interpretation was 97.4% . The BIOMIC system offers a 57.4% savings per test over the Vitek system . The BIOMIC system utilizes an older technology which is more efficient and yet yields results comparable to those of established automated MIC methods . The savings achievable in laboratories and hospitals nationwide may contribute significantly to the containment of national health care expenditures.

Chest Surg Clin N Am, 1996 Aug, 6(3), 585 - 613
Natural history of residual air spaces after pulmonary resection; Barker WL; It is emphasized that a decision for or against surgical intervention in the management of residual spaces, irrespective of cause, will not be required for several months after their occurrence in most cases . The stresses associated with the critical period of disability occasioned by a prolonged air leak, even if not voluminous, may preclude premature surgical intervention . The indications for initial surgical resection and the diseases for which it was required often are sufficiently debilitating to the patient to produce a protracted period of convalescence, necessitating prolonged observation before a decision for aggressive surgical therapy is mandated or indicated . In our experience, these pleural spaces are not a major threat to the health of the patient . In many cases, the concern over them and the fear that more egregious postoperative problems will ensue have resulted in premature and overzealous treatment that may lead to iatrogenic complications . If, instead, they are left alone and followed with judicious observation based on appropriate clinical, physiologic, and radiologic criteria, a more favorable outcome will result . Haste in arriving at a decision to intervene surgically therefore is not warranted . Many factors must be taken into account before surgical treatment is considered . The age of the patient, his or her ventilatory status, condition of the underlying lung, prospect for physical activity with gainful employment and accompanying quality of life, underlying disease (tuberculosis or cancer) for which even a curative resection may have been done, problems in maintaining drainage (including convenience or discomfort), or adverse metabolic effects of chronic infection are just a few considerations . More recently, economic factors attendant upon managed care programs mandate cost-effective therapies to reduce duration of hospital stay and to decrease resource utilization associated with repetitive surgical procedures and returns to the operating room, protracted use of expensive antimicrobial drugs, and increased outpatient visits and home services . Certainly, prevention of and avoidance of unwarranted interventions for intrathoracic spaces will assist in accomplishing these goals . Finally, it is apparent that patients can live in relatively good health for long periods of time with persisting vented or unvented spaces in association with air leak from alveolar seepage sources, and even with the presence of well-drained and controlled empyemas . The most important aspect of management is delineation of spaces that can be observed safely versus those that require surgical intervention . This discussion provides a basis for making that distinction . The algorithm illustrated in Figure 13 summarizes this management.

Zentralbl Veterinarmed A, 1996 Aug, 43(6), 331 - 6
The anti-inflammatory drugs phenylbutazone and dipyrone in the treatment of field cases of bovine mastitis; Shpigel NY et al.; The efficacy of phenylbutazone vs . dipyrone for the treatment of acute clinical mastitis were compared in a clinical trial . All cows were treated with 20 g sulfadiazine and 4 g trimethoprim i.m . upon diagnosis and half dosage once daily thereafter . In addition, the NSAIDs treated cows received once daily either 4 g phenylbutazone or 20 g dipyrone i.m . for the duration of the antimicrobial therapy . In all treatment groups the major causative organisms were coliforms . Recovery rates for the controls, the phenylbutazone and dipyrone treatment groups were 81.8%, 89.4% and 86.6%, respectively . Recovery was evaluated by the logistic regression analysis, the odds ratios (OR) and their 95% confidence interval (CI) of treatment success for phenylbutazone and dipyrone treatments relative to the control treatment were calculated . Odds ratio of recovery was high for phenylbutazone (OR = 2.42; CI = 0.98-5.96; P = 0.054) as well as for dipyrone (OR = 1.71; CI = 0.98-3.00; P = 0.060), demonstrating a strong trend towards improved recovery in NSAID groups . The odds of treatment failure for the phenylbutazone group relative to the dipyrone group was 0.71 with 95% CI of 0.28-1.78 . Clearly no significant difference could be demonstrated between phenylbutazone and dipyrone in this field trial.

Methods, 1996 Aug, 10(1), 8 - 14
Nitrogen Oxide in Host Defense against Parasites
Oswald IP, James SL.
Despite its small size and transitory nature, nitric oxide (NO) is a very versatile molecule . In addition to its function as a potent vasodilator and neurotransmitter, NO is important in inflammation and immunity . Indeed, in vitro experiments demonstrated that NO production by cytokine-activated rodent cells is a primary mediator of their antimicrobial and antitumoral activity . NO results from the oxidative deimination of l-arginine to l-citrulline by NO synthase (NOS), several isoforms of which have recently been isolated . Numerous cells types produce high levels of NO as a result of the expression of the inducible NO synthase (iNOS) after stimulation with bacterial product and/or cytokines, leading to parasite elimination . iNOS activity is highly regulated by cytokines, with some of them acting to induce enzyme expression (IFN-gamma, TNF-alpha), and others acting as inhibitory cytokines (TGF-beta, IL-4, IL-10, and IL-13) . While a strong correlation between antiparasitic activity and NO production by cytokine-activated cells has been readily demonstrated in vitro, the relationship between generation of NO in vivo and protection against parasitic infection has only recently been addressed . Although human cells such as hepatocytes have been shown to express iNOS, the presence of such a pathway in human monocyte/macrophages is a subject of great controversy.

Cell Immunol, 1996 Aug 1, 171(2), 231 - 9
Immunoregulatory role of nitric oxide in Legionella pneumophila-infected macrophages; Yamamoto Y et al.; Nitric oxide (NO) is an intercellular messenger molecule produced by a variety of cells, including macrophages . However, the role of NO in infection, especially its immunological role, is poorly understood . In the present study, the role of NO in Legionella pneumophila-infected macrophages was examined . Whereas infection of mouse macrophages in vitro with L . pneumophila did not induce detectable NO, when the macrophages were primed with interferon-gamma (IFN-gamma), the treated macrophages markedly inhibited bacterial replication and produced a large amount of NO . Treatment with NO inhibitors, such as NG-monomethyl-L-arginine (L-MMA) or aminoguanidine, as well as culture in arginine-free medium, significantly inhibited NO production; however, the anti-L . pneumophila activity induced by IFN-gamma was not diminished . Examination of cytokine levels in L . pneumophila-infected macrophages primed with IFN-gamma revealed a moderate increase of interleukin-6 (IL-6) production; however, inhibition of NO by L-MMA markedly increased IL-6 production . Reconstitution of NO in the L . pneumophila-infected macrophages primed with IFN-gamma and treated with L-MMA to inhibit endogenous NO production following addition of sodium nitroprusside reduced IL-6 production to normal levels . The levels of IL-6 mRNA in L-MMA-treated macrophages were the same as in nontreated macrophages, as demonstrated by quantitative RT-PCR . Thus, these results indicate that NO may regulate IL-6 production independently of its role in antimicrobial function in L . pneumophila-infected macrophages and their immunoregulation on IL-6 production may be due to a post-transcriptional mechanism.

Chem Pharm Bull (Tokyo), 1996 Aug, 44(8), 1567 - 70
Relationship between uptake of p-hydroxybenzoic acid esters by Escherichia coli and antibacterial activity; Fukahori M et al.; The relationship between the uptake and antimicrobial activity of p-hydroxybenzoic acid esters (parabens) was studied using Escherichia coli . The uptake into bacterial cells and the antibacterial activity of parabens were logarithmically proportional to the carbon number of the alkyl group from methyl to butyl paraben . The free energy change for the transfer of the methylene group of parabens from the aqueous to the cell phase was less than that obtained from the n-hexane and n-octanol-water partition systems . This demonstrates that the hydrophilicity of the cells is larger than n-hexane and n-octanol . The uptake of hydrophobic ethyl benzoate was less than that of the more hydrophilic butyl paraben possessing a phenolic hydroxyl group . Parabens may thus be incorporated into cells by both hydrophobic and hydrophilic interactions . The apparent concentration of parabens in the bacterial cells required to produce the same antibacterial activity decreased logarithmically with an increasing carbon number of the alkyl group . The dependence of the antibacterial activity of parabens on the alkyl chain length may thus be concluded to be due to the alkyl group, not only for uptake into bacterial cells but also for accumulation or concentration on biological receptors after incorporation into the cells.

Chem Pharm Bull (Tokyo), 1996 Aug, 44(8), 1440 - 7
Development of bioactive functions in hydrangeae dulcis folium . V . On the antiallergic and antimicrobial principles of hydrangeae dulcis folium . (2) . Thunberginols C, D, and E, thunberginol G 3'-O-glucoside, (-)-hydrangenol 4'-o-glucoside, and (+)-hydrangenol 4'-O-glucoside; Yoshikawa M et al.; Following the characterization of thunberginols A, B, and F, six bioactive principles, thunberginols C, D, and E, thunberginol G 3'-O-glucoside, (-)-hydrangenol 4'-O-glucoside, and (+)-hydrangenol 4'-O-glucoside, were isolated from Hydrangeae Dulcis Folium, the processed leaves of Hydrangea macrophylla SERINGE var . thunbergii MAKINO, together with four kaempferol and quercetin oligoglycosides . Their chemical structures have been determined on the basis of chemical and physicochemical evidence . Thunberginols C, D, E, and G and (-)-hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay using the Schultz-Dale reaction . These components also exhibited inhibitory activities on the histamine release from rat mast cells and on the histamine-induced contraction in isolated guinea pig tracheal chain . In addition, thunberginols C, D, E, and G showed antimicrobial activities against oral bacteria.

J Nat Prod, 1996 Aug, 59(8), 796 - 7
Montiporic acids A and B, cytotoxic and antimicrobial polyacetylene carboxylic acids from eggs of the scleractinian coral Montipora digitata; Fusetani N et al.; Two new polyacetylene carboxylic acids, montiporic acids A (1) and B (2), have been isolated from the eggs of the scleractinian coral Montipora digitata and their structures elucidated on the basis of spectroscopic data . They exhibited antimicrobial activity against Escherichia coli and cytotoxicity against P-388 murine leukemia cells.

Am J Gastroenterol, 1996 Aug, 91(8), 1549 - 52
Antimicrobial therapy for Helicobacter pylori infection versus long-term maintenance antisecretion treatment in the prevention of recurrent hemorrhage from peptic ulcer: prospective nonrandomized trial on 125 patients; Santander C et al.; OBJECTIVE: Our objective was to assess the effectiveness of therapy for Helicobacter pylori (HP) on the prevention of recurrent bleeding in patients with recent upper gastrointestinal hemorrhage from peptic ulcers . METHODS: We performed a prospective follow-up study without randomization on 125 consecutive patients (83 males and 42 females) who had presented with their first major episode of upper gastrointestinal hemorrhage from peptic ulcer (22 gastric and 103 duodenal ulcers) . All 125 patients were HP-positive . During the acute phase of bleeding, all patients were treated with standard supportive measures . After the acute bleeding phase, patients were allocated to two treatment groups: 1) antimicrobial therapy-84 patients received one of the following three regimens: 1) amoxicillin 500 mg t.i.d . for 10 days + omeprazole 20 mg b.i.d . for 30 days; 2) clarythromycin 500 mg t.i.d . for 12 days + omeprazole 20 mg b.i.d . for 30 days; or 3) amoxicillin 500 mg t.i.d . for 10 days + metronidazole 500 mg t.i.d . for 10 days + colloidal bismuth subcitrate 240 mg b.i.d . for 30 days . For long-term antisecretion maintenance treatment, 41 patients were allocated to either omeprazole 20 mg once a day or ranitidine 150 mg once a day, for 1 yr . RESULTS: During the follow-up period, peptic ulcers recurred in six patients in the antibiotic group (7.14%) and 13 patients in the maintenance group (31.7%) (p < 0.001) . The fraction of patients without recurrent bleeding was greater in the antibiotic group than in the maintenance group . Two patients in the antibiotic group (2.3%) and five in the maintenance group (12.1%) had recurrent hemorrhages (p < 0.1) . CONCLUSION: Cure of HP infection reduces the recurrence of peptic ulcer and of rebleeding from ulcer disease more effectively than does long-term maintenance therapy.

Infect Immun, 1996 Aug, 64(8), 3074 - 80
Counterprotective effect of erythrocytes in experimental bacterial peritonitis is due to scavenging of nitric oxide and reactive oxygen intermediates; Kim YM et al.; Erythrocytes (RBC) in the peritoneal cavity significantly increase the lethality of bacterial peritonitis . The lethality is known to be associated with, and perhaps due to, increased bacterial counts in the peritoneal cavity . The mechanism is unknown . In this study, we investigated the hypothesis that RBC scavenge reactive oxygen intermediates (ROI) and nitric oxide (NO), so that the counterprotective effect is due to a loss of the microbiostatic activity of both ROI and NO . To study this effect, rats were subjected to a peritoneal inoculation of live Escherichia coli without RBC (nonlethal dose) or with RBC (lethal dose) . The adjuvant effect of RBC was not modified by NG-monomethyl-L-arginine (NMA, an NO synthase inhibitor), superoxide dismutase, catalase, mannitol, or a combination of these agents . Furthermore, the increased number of bacteria in the peritoneal cavity in the presence of RBC was unaffected by these treatments . The administration of NMA with bacteria alone (no RBC) converted a nonlethal model into a lethal one associated with higher intraperitoneal bacterial counts . A similar effect was seen with superoxide dismutase and catalase but not with mannitol . During bacterial peritonitis in the absence of RBC, superoxide and NO formation (determined by the total nitrite plus nitrate formed) was detected in the ascites and inducible NO synthase mRNA expression was present in the peritoneal cells . In the absence of RBC, superoxide was detected and oxidation of dihydrorhodamine to rhodamine was observed, indicating that peroxynitrite was produced . Both were blocked by the inclusion of RBC . Preinjection with a low inoculum of killed bacteria protected the rats from a subsequent lethal peritoneal bacterial challenge; this effect was reversed by scavenging ROI and NO . The protective effect of killed bacterial pretreatment was lost when RBC were placed in the peritoneal cavity . In vitro bactericidal activity of NO- and ROI-generating macrophages was also inhibited by RBC or by inhibiting ROI and NO formation . Taken together, these data are consistent with the hypothesis that RBC can impair bacterial clearance by removing both NO and ROI, suggesting that NO in combination with superoxide may be important to the antimicrobial defenses of the peritoneal cavity.

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