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