Int J Antimicrob Agents, 2000 Jul, 15(2), 131 - 5 Evaluation of rational antibiotic use; Tunger O et al.; The emergence of antibiotic resistant bacteria is a major problem throughout the world and a rational use of antibiotics is therefore very important . This study was performed to estimate the appropriateness of antimicrobial drug use in Celal Bayar University Hospital in Manisa . The data of all inpatients (n=937) between October and December 1998 were collected according to the Kunin and Jones criteria . Of the patients, 16.6% (n=156) were receiving antibiotics, and in 63.5, 23.0 and 13.5% of these, a single, two and three agents were used, respectively . The purpose of antibiotic use was for prophylaxis in 23.9%, as an empiric decision in 71.4% and for therapeutic culture-based reasons in 4.7% . The rate of rational antibiotic use was 45.7% and it was statistically higher in those patients from whom specimens had been taken for culture than in patients receiving prophylactic or empiric antibiotics . On medical wards, rational antibiotic usage was 55.1%, while it was 26.3% in surgical wards (P<0.0001) . The low rate of appropriate antibiotic use in our university hospital reflects the urgent need of rationalization. Int J Antimicrob Agents, 2000 Jul, 15(2), 119 - 23 Efficacy of continuous infusion of ceftazidime for patients with neutropenic fever after high-dose chemotherapy and peripheral blood stem cell transplantation; Egerer G et al.; Neutropenia is an important complication of high-dose chemotherapy (HDCT) . Neutropenic patients presenting with fever are routinely hospitalized for treatment with broad-spectrum antibiotics . Neutropenia up to 10 days is associated with a low-risk profile, and antimicrobial therapy administered on an outpatient basis might be an alternative to admission to hospital . This prospective study evaluates the safety of a continuous infusion of ceftazidime in neutropenic patients after HDCT and peripheral blood stem cell transplantation (PBSCT) . From September 1995 to October 1999, 81 patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion per 24 h of ceftazidime using a portable infusion pump . If the fever persisted for 72 h, a glycopeptide antibiotic was added . The median patients' age was 44 years . Fifty-two of 81 patients (64%) responded to the monotherapy with ceftazidime . After addition of a glycopeptide antibiotic, a further 17 patients (21%) became afebrile . The causes of fever were septicaemia in 11 patients, pneumonia in two and fever of unknown origin in 68 patients . Fifty-eight episodes (72%) were successfully managed by outpatient treatment alone . The reason for admission to hospital was the change to imipenem/cilastin, which had to be administered three times per day (12 patients), severe mucositis with parenteral nutrition (eight patients), or a Karnovsky index </=60 (three patients) . In six of these cases, outpatient treatment was resumed after a brief period of in-patient care . In no case was the treatment terminated because of failure of the pump . With daily follow-up and close monitoring for development of complications, it is possible to discharge patients earlier after HDCT and PBSCT, thereby decreasing costs. Int J Antimicrob Agents, 2000 Jul, 15(2), 103 - 9 Macrolides and clindamycin suppress the release of Shiga-like toxins from Escherichia coli O157:H7 in vitro; Murakami J et al.; We investigated the effects of antimicrobial agents fosfomycin (FOS), cefdinir (CDIN), levofloxacin (LEVX), rokitamycin (ROK), roxithromycin (ROX), and clindamycin (CLI) on the release of Shiga-like toxins (SLTs) by enterohaemorrhagic Escherichia coli (EHEC) . EHEC was cultured for 14 h in the presence of ROX, ROK or CLI at sub-minimum inhibitory concentrations (subMICs) of 1.56-6.25 mg/l, followed by assay of the level of SLTs in the supernatants using cytotoxicity assay and reversed passive latex agglutination method . Exposure to ROX, ROK or CLI reduced the amount of released SLTs compared with untreated control cultures (P<0.05) . These agents however, did not decrease the number of viable EHEC, indicating the importance of bactericidal agents . When the bacteria was exposed to CDIN, FOS or LEVX, the level of SLTs in the culture supernatant increased with the destruction of bacterial cells in the order of CDIN, FOS, LEVX . When 0.5 mg/l of LEVX was added to cultures with or without pretreatment using ROX, ROK, or CLI, the release of SLTs was reduced by this pretreatment (P<0.05) . These results may have clinical implications for the treatment of EHEC infection. Int J Antimicrob Agents, 2000 Jul, 15(2), 91 - 101 Toward multinational antimicrobial resistance surveillance systems in Europe; Monnet DL; While there is a growing concern about increasing antimicrobial resistance and international spread of resistant microorganisms, we are still lacking timely multinational, good-quality susceptibility data to guide our decisions on controlling such resistance . This review describes and compares current sources of multicentric antimicrobial susceptibility data, identifies problems responsible for the postponing of the implementation of epidemiological antimicrobial resistance surveillance systems and finally presents requirements for such systems. Eur J Clin Pharmacol, 2000 Apr, 56(1), 97 - 101 Antibiotic utilization at the university hospital after introducing an antibiotic policy; Vlahovic-Palcevski V et al.; OBJECTIVE: Antibiotic formulary restrictions are among the most popular methods to control antibiotic utilization in hospitals . The aim of the present survey was to investigate the influence of "reserve antibiotic" on antimicrobial utilization at the University Hospital Center (UHC) Rijeka . METHODS: At the UHC Rijeka, reserve antibiotic was implemented in July 1997 . The antimicrobial drug consumption was monitored 6 months prior to and 6 months after the introduction of the method . Antimicrobial consumption was measured in defined daily doses (DDDs) among the major clinics . RESULTS: Reserve antibiotic has led to a decrease in total antibiotic consumption at the UHC Rijeka (45.9 DDDs/100 bed days vs 32.9 DDDs/100 bed days) . Antibiotic utilization decreased in the second semester at most clinics: at the Clinic for Infectious Diseases 41%, at the Anesthesiology and Intensive Care Unit 30%, at the Clinic for Internal Medicine 18% and at the Surgical Clinic 12% . At the Clinic for Gynecology and Obstetrics, the antibiotic utilization remained the same, while at the Pediatric Clinic an increase of 28% in antibiotic utilization was noted . CONCLUSION: Our study indicates that restriction of usage of some antibacterial agents is a successful method to decrease antibiotic consumption and a way to bring cost savings and helps prevent emergence of resistant microorganisms in hospitals . To improve antimicrobial prescribing, additional methods such as education are required. Pharmacotherapy, 2000 Jun, 20(6), 711 - 23 The pharmacist's role in promoting optimal antimicrobial use; Dickerson LM et al.; Optimal use of antimicrobials is essential in the face of escalating antibiotic resistance, and requires cooperation from all sectors of the health care system . Although antibiotic-restriction policies in the hospital setting are important in altering microbial susceptibility patterns, an overall reduction in antibiotic prescriptions in the outpatient setting is more likely to significantly impact antibiotic resistance . Education of providers, application of clinical practice guidelines, audit and feedback activities, and multifaceted interventions all have had an effect in altering antibiotic prescribing in a research setting . Clinicians must alter antibiotic prescribing for the treatment of infectious diseases, and patients must change their perception of the need for these drugs . Pharmacists can play a major role through clinician education and focused clinical services . With cooperation of health care teams, the effectiveness of available antibiotics may be sustained and the threat of resistance minimized. Oncology (Huntingt), 2000 May, 14(5), 659 - 66, 671-2; discussion 672-7 Management of infections in patients with acute leukemia; Sarkodee-Adoo CB et al.; Several recent studies have addressed the management of infectious problems in patients with acute leukemia . Although those studies have served to emphasize the fundamental management principles formulated and proven almost 30 years ago, they have also contributed important new insights . This article describes recent developments in the management of infectious illnesses in patients who are neutropenic due to leukemia or its treatment . The discussion will focus on the increasing armamentarium of antimicrobial drugs and adjunctive agents . These expanding therapeutic options must be viewed in the context of newly emerging resistant organisms and special problems, such as the increased use of indwelling venous catheters. J Food Prot, 2000 Jun, 63(6), 741 - 6 Combined effect of nisin and pulsed electric fields on the inactivation of Escherichia coli; Terebiznik MR et al.; The Doehlert design was applied in order to investigate the combined effect of nisin and high voltage pulsed electric fields (PEF) on the inactivation of Escherichia coli in simulated milk ultrafiltrate media . Nisin alone was totally inactivated by PEF, but in the presence of bacterial cells a protective effect was observed . However, the effectiveness of nisin was still decreased when bacterial cells were subjected to the combined treatment . In spite of this phenomenon, an almost additive response emerged as a consequence of the combined treatment . A 4-log cycle reduction may be accomplished with around 1,000 IU/ml (7.15 microM) of nisin and three pulses of 11.25 kV/cm or 500 IU/ml for five pulses of the same intensity . The observed efficacy arising from the combination of both treatments suggests the possibility of using PEF for improving the action spectrum of natural antimicrobials. J Food Prot, 2000 Jun, 63(6), 735 - 40 Combined effect of hop resins and sodium hexametaphosphate against certain strains of Escherichia coli; Fukao T et al.; The combined antimicrobial effects of hop resins with sodium hexametaphosphate, glycerol monocaprate, and lysozyme were investigated aiming to make an effective agent against Escherichia coli . When they are used separately, the antimicrobial activity against E . coli was minimal . However, the combination of hop resins with sodium hexametaphosphate exhibited strong antimicrobial activity against E . coli, but no effect was found in combinations of hop resins with the other agents . The activity was strongest when the combination was added at the beginning of growth of the bacteria, resulting in a prolonged lag phase . However, when the antimicrobials were added during the log phase, growth was depressed considerably . By addition of these materials, cell components with absorbance near 260 nm were leaked out . This possibly may have resulted from damage to the cell membranes of the bacteria . The combined effect was also detected in model food systems such as mashed potatos . The use of hop resins and sodium hexametaphosphate in combination may thus be useful for controlling E . coli. Laryngoscope, 2000 Jun, 110(6), 875 - 80 Current status of topical nasal antimicrobial agents; Goh YH et al.; The nasal cavity and paranasal sinuses are probably one of the last frontiers in the head and neck region where the use of topical antimicrobial agents is not yet established . Although the anatomy of the nasal cavity and the paranasal sinuses can theoretically be exploited for the administration of antimicrobials in rhinosinusitis, very few studies have been conducted to test the feasibility of this mode of therapy . We review the anatomical and physiological factors that should be considered in the use of topical nasal antimicrobial agents and the current status of topical nasal antimicrobial usage, and we make recommendations for the administration of topical nasal antimicrobial agents. J Vet Med Sci, 2000 May, 62(5), 479 - 85 Antibacterial effect of chloramphenicol, thiamphenicol and florfenicol against aquatic animal bacteria; Ho SP et al.; The minimum inhibitory concentration (MIC) was measured to evaluate the antibacterial activities of chloramphenicol (CP), thiamphenicol (TP) and florfenicol (FFC) against the aquatic bacterial isolates from soft-shell turtles, fish and shellfish . Amoxicillin (AMPC), oxytetracycline (OTC) and oxolinic acid (OA) were included to compare with above protein synthesis inhibitors . The results showed that the order of MIC range of the isolates from soft-shell turtles for tested drugs was OA>FFC, CP>TP> AMPC, OTC . The percentage of the resistant strains indicated that OA was the lowest (7.14%) and OTC was the highest (85.07%) . The order of antibacterial activity against the isolates from fish was OA>FFC>CP>AMPC>OTC>TP . The percentage of the resistant strains revealed that OA (13.64%) and OTC (80.91%) were the lowest and the highest, respectively . For the isolates from shellfish, the order of antimicrobial activity was OA>CP, FFC>AMPC, OTC, TP . TP showed the greatest percentage of the resistant strains (58.7%), but that of OA was the lowest (4.35%) . The most common resistant patterns of the isolates from turtles, fish and shellfish were AMPC-OTC, CP-TP-AMPC-OTC, and FFC-CP-TP-AMPC-OTC, respectively . There were partially-complete resistance of the resistant isolates among CP, TP and FFC . The findings indicated that previous treatment might affect the choice of drug to use for aquatic bacterial diseases. Zh Mikrobiol Epidemiol Immunobiol, 1999 Sep-Oct, (5), 61 - 7 {The antimicrobial activity of nitric oxide and its role in the infectious process}; Bondarenko VM et al.; In this article information on an important role of nitric oxide (NO) in inhibiting the growth of a number of pathogenic microorganisms, including intracellular parasites, and their elimination from the host body is presented . Differences between the mechanisms of the production of NO and free-radical compounds having antimicrobial action are given . The regulation of the activity of constitutive NO-synthase and inducible NO-synthase and the relationship between the latter and the phagocytic activity and production of anti-inflammatory cytokines are described . An important role of NO in the development of the nonspecific resistance of the body is mentioned. Commun Dis Intell, 2000 Apr, 24(4), 93 - 5 Surveillance of pneumococcal disease in Australian states and territories; McIntyre P et al.; Information on pneumococcal disease, including immunisation programs, and optimum future surveillance in each Australian State and Territory were discussed at the Pneumococcal Disease in Australia Workshop on 26-27 March 1999 . Workshop participants further expanded on the surveillance aspects of the Workshop in this report . Most participants favoured notification by laboratories of pneumococcal isolates from sterile sites, to provide baseline surveillance data before immunisation programs are fully implemented . It was also thought that trends in antimicrobial resistance should be notified. Commun Dis Intell, 2000 Apr, 24(4), 89 - 92 Pneumococcal disease in Australia; Forrest JM et al.; The proceedings of the Pneumococcal Disease in Australia Workshop, held on 26-27 March 1999 are presented in this report . The world-wide epidemiology of the pneumococcus, with its predilection for the very young and the very old, differs between the developing and the developed world, and between indigenous and non-indigenous populations . Sources of data on pneumococcal disease in each of the Australian States, clinical aspects of invasive and non-invasive disease, and the role of the public health laboratory in surveillance of serotypes and antimicrobial sensitivity, both nationally and over time, were discussed at the Workshop . Polysaccharide pneumococcal vaccines are recommended for those over 65 years of age and for at-risk groups, but are supplied free of charge only in Victoria and for indigenous Australians over 50 years of age . Children will require conjugate vaccines, which are likely to be licensed in the United States of America early in 2000 . In Australia indigenous children, especially in rural areas, will be the priority group for conjugate vaccines. Environ Res, 2000 May, 83(1), 72 - 8 The effects of chlorothalonil on oyster hemocyte activation: phagocytosis, reduced pyridine nucleotides, and reactive oxygen species production; Baier-Anderson C et al.; The production of reactive oxygen species (ROS) by a putative NADPH oxidase-like enzyme system is thought to contribute to antimicrobial activity in oyster hemocytes . NADPH oxidase in vertebrate phagocytes generates superoxide anion from molecular oxygen and NADPH, which is then converted to additional ROS, including H2O2 and HOCl . The fungicide chlorothalonil (TCIN) is a thiol-reactive compound that binds to protein sulfhydryl groups, which can result in enzyme inactivation . NADPH oxidase, containing several sulfhydryl groups, is a potential target of TCIN . Previous studies have demonstrated that in vitro exposure of fish (Morone saxatilus) macrophages to TCIN (10-500 microg/L) suppressed immunostimulated ROS and baseline NAD{P}H concentration but did not inhibit phagocytosis; the production of NADPH in stimulated cells was decreased only at the highest concentration . In this study, we evaluated the effects of TCIN (10-500 microg/L) on oyster hemocyte functions . As with striped bass macrophages, in vitro exposure to TCIN suppressed hemocyte ROS production in a dose-dependent manner, but did not affect phagocytosis . In contrast to the striped bass data, baseline NAD{P}H concentration was relatively unaffected and immunostimulated NAD{P}H production was marginally suppressed at the higher exposure concentrations . Despite these minor differences, these results suggest that TCIN may also be inhibiting an NAD{P}H oxidase-like enzyme in oyster hemocytes. Drugs, 2000, 59 Suppl 3, 37 - 46; discussion 47-9 Place of parenteral cephalosporins in the ambulatory setting: clinical evidence; Nathwani D; During the last decade, 6 parenteral third generation cephalosporins have been introduced into clinical practice . The three most frequently used agents are cefotaxime, ceftazidime and ceftriaxone . Although primarily used in hospitals, these agents are increasingly employed in the ambulatory setting . In particular, ceftriaxone, because of its favourable pharmacokinetic profile allowing once-daily administration by a bolus injection, has demonstrated both tolerability and efficacy in the ambulatory setting during extensive worldwide use . Sophisticated parenteral infusion systems enable cephalosporins that require more frequent administration to be delivered in this setting . In noncomparative studies involving a range of patient populations and serious infections (mostly bone, joint and soft tissue, and pneumonia and febrile episodes in neutropenia), these cephalosporins achieved equivalent efficacy and tolerability, and considerable cost savings, since patients were able to receive all or part of their treatment in the home or outpatient setting . However, more comparative studies of ambulatory parenteral therapy in the inpatient setting or ambulatory oral therapy are necessary to further clarify the true cost effectiveness of this type of healthcare delivery . This is increasingly relevant in countries where parenteral antimicrobials are not the 'standard of care' in managing many serious infections . Published experience to date confirms that third generation cephalosporins, particularly ceftriaxone, should have an essential place in the therapeutic formulary of any ambulatory parenteral antibiotic programme. Drugs, 2000, 59 Suppl 3, 29 - 35; discussion 47-9 Pharmacoeconomic considerations in the ambulatory use of parenteral cephalosporins; Tice AD; It has been clearly documented that outpatient parenteral antibiotic therapy (OPAT) saves money compared with hospital care for patients who need intravenous antimicrobial therapy . The reduced expenses come primarily from savings in facility and hospital staffing costs . In addition to shortening hospital stay, OPAT programmes can be developed so that hospital care is avoided altogether . However, even with the clear potential for savings, to have a successful programme it is necessary to align the interests of the payers, the physicians, the administrators and the patients . The cost of OPAT programmes can also be reduced through patient evaluation and careful selection of the appropriate delivery model, antibiotic, dosage intervals and infusion technology . The fact that antibiotics such as ceftriaxone, the aminoglycosides and vancomycin can be given once daily in the elderly offers particular advantages in terms of convenience as well as cost . In order to achieve cost savings, managed care will increasingly rely on home and outpatient therapy . This pressure will need to be counterbalanced by quality assurance programmes and outcomes measurements. Drugs, 2000, 59 Suppl 3, 1 - 8; discussion 47-9 Ambulatory use of parenteral antibacterials: contemporary perspectives; Leggett JE; Outpatient parenteral antimicrobial therapy (OPAT) offers increased patient comfort and convenience in appropriately selected patients who require parenteral antibacterial therapy, as well as opportunity for cost savings . Home-based programmes, with drugs being administered by the patient or the caregiver, have become the norm in the USA . Choice of drugs for OPAT is based on antimicrobial spectrum, dosage regimen, drug stability, toxicity profile, and cost . Over the past decade, availability of sophisticated programmable pumps has allowed a wider range of antimicrobial agents to be used in the ambulatory setting . The most popular antibacterial agents in OPAT programmes in the USA are vancomycin and beta-lactams. Fitoterapia, 2000 Jun, 71(3), 315 - 6 Antibacterial activity of Enantia polycarpa bark; Ajali U; Antimicrobial screening of Enantia polycarpa bark showed activity of the polar extracts against some microorganisms. Biochemistry, 2000 Jun 20, 39(24), 7159 - 69 Design of salt-insensitive glycine-rich antimicrobial peptides with cyclic tricystine structures; Tam JP et al.; Cyclic peptide backbone and cystine constraints were used to develop a broadly active salt-insensitive antimicrobial peptide {Gly(6)}ccTP 1a with eight Gly residues in an 18-residue sequence . The importance of rigidity and amphipathicity imparted by the cyclic and cystine constraints was examined in two peptide series based on tachyplesin, a known beta-stranded antimicrobial peptide . The first series, which retained the charge and hydrophobic amino acids of tachyplesin, but contained zero to four covalent constraints, included a cyclic tricystine tachyplesin (ccTP 1) . Corresponding {Gly(6)} analogues were prepared in a parallel series with all six bulky hydrophobic amino acids in their sequences replaced with Gly . Circular dichroism measurements showed that ccTP 1 and {Gly(6)}ccTP 1a exhibited well-ordered beta-sheet structures, while the less constrained {Gly(6)} analogues were disordered . Except for linear peptides assayed under high-salt conditions, peptides with increased or decreased conformational constraints retained broad activity spectra with small variations in potency of 2-10-fold compared to that of tachyplesin . In contrast, Gly replacement analogues resulted in large variations in activity spectra and significant decreases in potency that roughly correlated with the decreases in conformational constraints . Except against Escherichia coli, the Gly-rich analogues with two or fewer covalent constraints were largely inactive under high-salt conditions . Remarkably, the most constrained {Gly(6)}ccTP 1a retained a broad activity spectrum against all 10 test microbes in both low- and high-salt assays . Collectively, our results show that {Gly(6)}ccTP 1acould serve as a template for further analogue study to improve potency and specificity through single or multiple replacements of hydrophobic or unnatural amino acids. J Burn Care Rehabil, 2000 May-Jun, 21(3), 254 - 7 Biodebridement: a case report of maggot therapy for limb salvage after fourth-degree burns; Namias N et al.; The wound healing and antimicrobial properties of maggots are well known . Maggot debridement therapy has been used for the treatment of various conditions . For maggot debridement therapy, the larvae of the blowfly are applied over necrotic or nonhealing wounds . We used maggot debridement therapy with the larvae of Phaenicia sericata for limb salvage after bilateral lower extremity fourth-degree burns. J Burn Care Rehabil, 2000 May-Jun, 21(3), 199 - 204 A 10-year experience with toxic epidermal necrolysis; Schulz JT et al.; Toxic epidermal necrolysis is a devastating medication-induced desquamation disorder with a reported mortality rate of 30% to 60% in adults . Data from previously reported series suggest that age, delay in referral to a burn center, total body surface area (TBSA) involvement, and systemic steroid treatment are poor prognostic indicators . We reviewed the records of 39 patients treated in our burn center over the past 10 years and found that the mortality rate was significantly correlated with age, thrombocytopenia, and delay in presentation . Steroid treatment and TBSA involvement were not significantly related to the mortality rate . Thirty-nine adult patients with greater than 20% TBSA epithelial necrosis were cared for in our center from January 1987 to March 1998 . Wounds were treated with topical antimicrobial medications and porcine xenografts in a bacteria-controlled nursing unit . We reviewed the records of these patients for 28 clinical characteristics and looked for clinical correlates of mortality by single analysis of variance . The mortality rate was 44% (17 of 39 patients); the cause of death was most commonly multiple-organ dysfunction syndrome, for which a microbial etiologic agent was not always identified . Autopsies were performed on 11 of the 17 patients who died; there was evidence of multiple-organ damage . The patients who survived and the patients who died did not differ significantly in TBSA epithelial necrosis (66%+/-6% vs 72%+/-5%, respectively), admission platelets, number of nosocomial infections, number of complications, preadmission exposure to steroids, or extent of mucosal involvement . When compared with the patients who died, the patients who survived were (1) 20 years younger (47.5+/-4.2 years vs 64.5+/-5.3 years), (2) admitted to the hospital sooner after the onset of their rash (3.5+/-0.4 days vs 5.9+/-1.0 days), (3) much less likely to experience early thrombocytopenia (platelet nadir, 154+/-24 vs 70+/-18), (4) more likely to be febrile on presentation, and (5) less likely to have been treated with antibiotics before referral to our unit . These differences were statistically significant . The most common etiologic agents were antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs . Our results for a group of older patients with toxic epidermal necrolysis with extensive skin involvement suggest that age, delay in hospitalization, thrombocytopenia, and early empiric antibiotic treatment are associated with a poor prognosis. Protein Sci, 2000 May, 9(5), 956 - 63 Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA; Ferguson AD et al.; One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates . These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of gram-negative bacteria . These "Trojan Horse" antibiotics may prove useful as an efficient means to combat multi-drug-resistant bacterial infections . Here we present the crystallographic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli . To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter . Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety . As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom . Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form . The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates. Appl Biochem Biotechnol, 2000 Spring, 84-86, 769 - 78 Screening of potential antibiotic action of cellulolytic fungi; Garcia-Kirchner O et al.; Twenty different strains of filamentous fungi were initially selected for evaluation of cellulolytic activity using a single test in a simple mineral salts culture medium with filter paper as the only carbon source . Those fungi strains that were capable of completely breaking the filter paper strip within 4-8 d were assayed also for antimicrobial action, using Staphyloccocus aureus ATCC 6538P according to the so-called agar piece method . We screened three different strains with both capacities: the production of cellulolytic activity and antibiotic action . The experimental results suggest that the fungi Penicillium sp . F0PC01, Aspergillus sp . F0Q001, and Cephalosporium sp . F03800 have both capabilities because they grew rapidly on cellulose as the only carbon source and were able to produce an area of growth inhibition in S . aureus of approx 2.04, 1.57, and 2.39 cm, respectively, on agar plates using the agar piece method . Subsequently, the antibiotic production obtained with those cellulolytic strains was evaluated by submerged fermentation at the flask level, in a simple culture medium containing lactose without biosynthesis precursor, obtaining 3670, 2830, and 4060 antibiotic units/mL, referred to as penicillin G, whereas for cellulolytic activity, the results were 1.34, 1.81 and 0.57 FPU/mL, respectively. Helicobacter, 2000 Jun, 5(2), 94 - 7 Controlled trial of the effect of cinnamon extract on Helicobacter pylori; Nir Y et al.; BACKGROUND: Helicobacter pylori has been associated with the pathogenesis of antral gastritis, duodenal ulcer, and gastric lymphoma . Eradication of H . pylori has been shown to reverse or prevent relapse of these diseases . Antimicrobials employed in the eradication of H . pylori are not without adverse effects . Newer treatment modalities, therefore, are required . In vitro studies have shown the effectiveness of cinnamon extract against H . pylori and its urease . In this pilot study, we tested the activity of an alcoholic extract of cinnamon in a group of patients infected with H . pylori . MATERIALS AND METHODS: Fifteen patients (11 women, 4 men) aged 16 to 79 years were given 40 mg of an alcoholic cinnamon extract twice daily for 4 weeks; eight patients aged 35 to 79 (7 women, 1 man) received placebo . The amount of H . pylori colonization was measured by the 13C urea breath test before and after therapy . RESULTS: The mean urea breath test counts in the study and control groups before and after therapy were 22.1 and 23.9 versus 24.4 and 25.9, respectively . The cinnamon extract was well tolerated, and side effects were minimal . CONCLUSIONS: We concluded that cinnamon extract, at a concentration of 80 mg /day as a single agent, is ineffective in eradicating H . pylori . Combination of cinnamon with other antimicrobials, or cinnamon extract at a higher concentration, however, may prove useful. Helicobacter, 2000 Jun, 5(2), 79 - 83 Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone in Brazil; Mendonca S et al.; BACKGROUND: Helicobacter pylori infection is associated with a wide range of digestive diseases and is very prevalent in developing countries, although few data exist on the susceptibility of H . pylori to antimicrobials commonly used in eradication schedules in these countries . The aim of this study was to evaluate the resistance of H . pylori to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone in dyspeptic Brazilian patients . Material and Methods . Ninety consecutive H . pylori-positive patients were enrolled . Resistance was evaluated by an agar dilution test . RESULTS: Resistance to metronidazole was detected in 38 patients (42%); to amoxicillin in 26 individuals (29%); to clarithromycin in 6 patients (7%); to tetracycline in 6 patients (7%); and to furazolidone in 4 individuals (4%) . Thirteen strains were resistant to two agents, and eight strains were resistant to three antimicrobials . CONCLUSIONS: These results confirm the need for culture and susceptibility testing to define H . pylori resistance patterns in particular geographical areas before the general use of an eradication schedule . They also suggest the possibility of resistance to such antimicrobials as amoxicillin or tetracycline in geographical areas with a high prevalence of H . pylori infection and still not fully evaluated for antimicrobial susceptibility. Phytochemistry, 2000 May, 54(1), 53 - 6 Antimicrobial intermediates of the general phenylpropanoid and lignin specific pathways; Barber MS et al.; The minimum inhibitory concentration (MIC) of the major intermediates of the general phenylpropanoid and lignin specific pathways of plants were determined employing a range of yeasts and bacteria . Of the three main classes of compounds tested, the hydroxycinnamaldehydes were the most effective, possessing notable antifungal and antibacterial activity . Determination of the minimum killing concentration (MKC) of the hydroxycinnamaldehydes revealed MIC/MKC ratios suggesting these compounds to be fungicidal, but not bactericidal, in their mode of action . In contrast, the hydroxycinnamic acids and hydroxycinnamyl alcohols possessed little antimicrobial activity, with the exception of the hydroxycinnamic acids, which were antibacterial. Antivir Ther, 2000 Mar, 5(1), 77 - 83 The role of resistance testing in clinical trial design and product labelling: a regulatory perspective; Laessig KA et al.; Assays that attempt to characterize HIV susceptibility or resistance are among the latest technologies that are likely to impact HIV clinical trial design, antiretroviral drug development and patient management . However, at present the Food and Drug Administration (FDA) have yet to approve any phenotypic or genotypic HIV resistance assay and the role of resistance testing in clinical management of patients and in drug development is ill defined . In November 1999, the Division of Antiviral Drug Products at the FDA convened a meeting of its advisory committee to consider the available information about HIV resistance testing, and to generate some recommendations about how these assays could be utilized in antiretroviral drug development . In addition, the committee was presented with several hypothetical regulatory scenarios in order to illustrate how HIV resistance testing might be incorporated in antiretroviral drug development and drug labelling . In this article, we discuss the regulatory history of resistance testing in antimicrobial drug development, the current use of resistance testing for antiretrovirals, as well as a summary of the hypothetical scenarios that were presented to the committee and the discussion of the committee members regarding those scenarios. Vestn Otorinolaringol, 2000, (3), 50 - 1 {Effect of recombinant interleukin-1 beta on microbial flora of the middle ear in patients with chronic purulent otitis media}; Riazantsev SV et al.; Betaleukin was given to 60 patients with various forms of otitis media purulenta chronica (OMPC) . Symptoms of the purulent exacerbation were relieved in 43.3% of the patients, the clinical course improved in 18.3% . No response was achieved in 40% of the treated patients . Betaleukin proved highly effective in management of exacerbations of uncomplicated OMPC though it has no direct antimicrobial activity. Ann Biol Clin (Paris), 2000 May-Jun, 58(3), 291 - 7 {Drug resistance in Mycobacterium tuberculosis: diagnostic methods}; Loiez-Durocher C et al.; The increasing frequency of multidrug-resistant strains of M . tuberculosis becomes dramatic in industrialized countries as well as in developing countries, particularly among patients infected with human immunodeficiency virus . It needs to formulate rapid strategies for diagnosing multidrug-resistant tuberculosis . For these new drug resistance, novel detection methods are developed in order to identify the resistant strains and to undertake efficacious antituberculosis therapies more rapidly . The phenotypic methods are based on the measurement of the microbial growth on nutritional supplement with antimicrobial agents; however, these proportional methods, such as the method in solid medium, the Bactec radiometric method or the MGIT method (mycobacterial growth indicator tube), are time consuming and give results in 5 to 21 days . In contrast, the genotypic tests, using knowledge of the genes involved in the resistance, reduce the time to detection of resistance from weeks to days . After amplification of the segment of the gene encoding the drug target by PCR, these methods are based on the identification of the different mutations conferring the antimicrobial resistance in M . tuberculosis . These methods are applied with success for detection of rifampicin resistance, conferring by mutations in a defined region of the rpoB gene for 99% of cases; on the contrary, results are less for other antituberculous drugs because of the insufficiency of knowledge of the molecular basis of drug resistance. J Am Vet Med Assoc, 2000 Jun 1, 216(11), 1795 - 8, 1760 Pythiosis with bone lesions in a pregnant mare; Worster AA et al.; A 9-year-old pregnant mare was referred for evaluation of a nonhealing wound of 8 weeks' duration on the lateral aspect of the left forelimb . A soft tissue mass encircled the proximal two thirds of the metacarpus; radiography revealed a moderate periosteal reaction affecting metacarpal bone i.v . Histologic and immunohistochemical examinations revealed eosinophilic granulomatous inflammation and Pythium sp in the soft tissues . The mare was treated for 12 days with antimicrobials, medicated wound dressings, debridement, and i.v . administration of sodium iodide; radiography revealed progression of the bone lesions . The mare was treated by regional arterial perfusion with miconazole and excision of affected soft tissues and the distal two thirds of metacarpal bone i.v . The mare recovered without complications and gave birth to a healthy foal . Regional perfusion of antifungal agents provides high concentrations in soft and osseous tissues and permits use of low dosages of agents administered by other routes, which reduces cost, adverse effects, and teratogenic effects. Medicine (Baltimore), 2000 May, 79(3), 170 - 200 Genetic, biochemical, and clinical features of chronic granulomatous disease; Segal BH et al.; The reduced nicotinamide dinucleotide phosphate (NADPH) oxidase complex allows phagocytes to rapidly convert O2 to superoxide anion which then generates other antimicrobial reactive oxygen intermediates, such as H2O2, hydroxyl anion, and peroxynitrite anion . Chronic granulomatous disease (CGD) results from a defect in any of the 4 subunits of the NADPH oxidase and is characterized by recurrent life-threatening bacterial and fungal infections and abnormal tissue granuloma formation . Activation of the NADPH oxidase requires translocation of the cytosolic subunits p47phox (phagocyte oxidase), p67phox, and the low molecular weight GT-Pase Rac, to the membrane-bound flavocytochrome, a heterodimer composed of the heavy chain gp91phox and the light chain p22phox . This complex transfers electrons from NADPH on the cytoplasmic side to O2 on the vacuolar or extracellular side, thereby generating superoxide anion . Activation of the NADPH oxidase requires complex rearrangements between the protein subunits, which are in part mediated by noncovalent binding between src-homology 3 domains (SH3 domains) and proline-rich motifs . Outpatient management of CGD patients relies on the use of prophylactic antibiotics and interferon-gamma . When infection is suspected, aggressive effort to obtain culture material is required . Treatment of infections involves prolonged use of systemic antibiotics, surgical debridement when feasible, and, in severe infections, use of granulocyte transfusions . Mouse knockout models of CGD have been created in which to examine aspects of pathophysiology and therapy . Gene therapy and bone marrow transplantation trials in CGD patients are ongoing and show great promise. Int J Androl, 2000 Jun, 23(3), 178 - 86 Escherichia coli-induced alterations of human spermatozoa . An electron microscopy analysis; Diemer T et al.; This study evaluated if the negative influence of Escherichia coli on the motility of human spermatozoa is a consequence of E . coli-induced ultrastructural alterations . Suspensions of spermatozoa were artificially infected with E . coli from a serotyped, pathogenic strain and incubated at 37 degrees C for 6 h . After incubation, spermatozoa were fixed in glutaraldehyde, stained with osmium tetroxide and ruthenium red and embedded in Spurr(R)-resin followed by ultramicrotomy . The sections were analysed subsequently by use of transmission electron microscopy . Uninfected suspensions of spermatozoa in medium and bacterial suspensions served as controls . Negative contrast technique was performed to facilitate visualization of ultrastructural details of the bacterial capsule after experimental exposure to spermatozoa . Electron microscopic evaluation revealed multiple and profound alterations in the ultrastructure of spermatozoa such as membrane defects and cytoplasmic vacuoles exclusively in spermatozoa of infected samples (> 90%) . Morphological alterations involved all superficial structures of spermatozoa, in particular the plasma membrane of the mid-piece and neck as well as the inner and outer acrosomal membrane of the acrosome, indicating that morphological defects account for the immobilization of spermatozoa by E . coli . The results suggest that E . coli infection of ejaculates results in immobilization and impaired acrosomal function in human spermatozoa, findings that support the indication for antimicrobial chemotherapy in symptomatic and silent infections that affect the ejaculate. J Nat Prod, 2000 May, 63(5), 690 - 1 An antimicrobial C(14) acetylenic acid from a marine sponge Oceanapia species; Matsunaga S et al.; A C(14) acetylenic acid has been isolated as an antimicrobial principle from a marine sponge Oceanapia sp . Its structure was determined on the basis of spectral data. J Nat Prod, 2000 May, 63(5), 631 - 5 Aminosterols from the dogfish shark Squalus acanthias; Rao MN et al.; Seven new aminosterols related to squalamine (8) were isolated from the liver of the dogfish shark Squalus acanthias . Their structures (1-7) were determined using spectroscopic methods, including 2D NMR and HRFABMS . These aminosterols possess a relatively invariant cholestane skeleton with a trans AB ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated . The structure of the lone spermine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5alpha,7alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate . Some members of this family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine. Trop Doct, 2000 Apr, 30(2), 114 - 6 Antimicrobial resistance in the tropics; Shears P; Bacterial resistance to antimicrobial agents is an increasing problem in many areas of the tropics . In most countries there is little information available to determine the patterns of resistance in different pathogens, nor are local data available to influence prescribing . This paper will review the development of antimicrobial resistance in the tropics, consider the current priority problems, and suggest strategies that may be taken to improve the surveillance of resistance. Am J Health Syst Pharm, 2000 May 1, 57(9), 875 - 81 Antimicrobial treatment patterns, resource utilization, and charges associated with acute sinusitis in asthma patients; Halpern M et al.; Antimicrobial treatment patterns, resource utilization, and charges associated with acute sinusitis in patients with asthma were studied . Asthma patients with at least one claim for acute sinusitis were identified by International Classification of Diseases, 9th Revision code in data for 1992-1994 from a large health care insurer in New England . A sinusitis episode was defined on the basis of the pattern of antimicrobial prescribing . Antimicrobials used to treat sinusitis, rates of resource utilization, and overall charges for therapy were determined . A total of 2,633 sinusitis episodes were identified in the records of 34,348 asthma patients . The most frequently prescribed antimicrobial for initial treatment of acute sinusitis was amoxicillin trihydrate (32.2% of patients) . Initial therapy was successful in 2,199 episodes (83.5%), initial therapy failed in 250 episodes (9.5%), and relapse occurred in 184 episodes (7.0%) . Successfully treated patients had fewer outpatient visits on average (1.42 per episode) and fewer laboratory and diagnostic tests (0.046) than did patients in whom initial therapy failed (1.76 and 0.056 per episode, respectively) or patients who relapsed (1.68 and 0.049) . The mean total charge for sinusitis care was $147.61 per episode for successfully treated patients, $242.95 per episode for patients unresponsive to treatment, and $205.49 per episode for patients who relapsed . Antimicrobial treatment of acute sinusitis varied widely in patients with asthma . Resource utilization was associated with the success of treatment. J Urol, 2000 Jul, 164(1), 186 - 91 Angiotensin II type 1 receptor antagonist (losartan) down-regulates transforming growth factor-beta in experimental acute pyelonephritis; Khalil A et al.; PURPOSE: To study the effect of an angiotensin II type 1 receptor antagonist, losartan, on cytokine expression, kidney growth and renal scarring in experimental acute pyelonephritis . MATERIALS AND METHODS: Female Bki NMRI mice, 8 weeks old were infected with E . coli CFT 073 via the urethra . Mice were divided into four groups; either left untreated; or treated with NaCl 0.9%; or an angiotensin II type 1 receptor antagonist, losartan, in doses of 1 mg . or 40 mg . /kg . body weight . The treatment was given daily i.p . for 48 hours, 3 weeks or 8 weeks respectively . Kidneys were weighed and sectioned for histo-pathology and in situ hybridization for mRNA of IL-1beta, TNF-alpha, IL-4, IL-6, IL-10, IL-12, TGF-beta and IFN-gamma . Homogenized kidneys were used for EIA of TGF-beta and bacterial growth . RESULTS: The mRNA expression of the studied cytokines generally peaked at 48 hours in all four groups . In animals treated with losartan, kidney TGF-beta, IFN-gamma and IL-6 decreased significantly at 3 and 8 weeks as compared with controls, untreated or those treated with NaCl, (p <0.005 respectively) . Infection was associated with a declining kidney weight, also in the presence of losartan . A 50% reduction of the spread of renal scarring was observed in the losartan treated group, but this did however not reach significance . The proportion of kidneys showing bacterial growth was not influenced by losartan although in these kidneys the mean bacterial counts at 3 weeks were significantly higher in the losartan treated mice (p <0.006) . CONCLUSIONS: Losartan is associated with downregulation of TGF-beta, IFN-gamma and IL-6 and may, in combination with antimicrobial therapy, reduce the risk of cortical renal scarring in recurrent acute pyelonephritis in infants. J Urol, 2000 Jul, 164(1), 57 - 8 Scrotal dog bites; Cummings JM et al.; PURPOSE: Dog bites to the scrotum are rare but they potentially result in morbidity if improperly managed . MATERIALS AND METHODS: Between 1991 and 1999 we treated 4 men and 3 boys with dog bites to the scrotum . All 7 patients presented to the emergency department shortly after the injury . Of the 4 adults 3 were ingesting alcohol and 2 were obviously intoxicated, and 1 had a T4 spinal cord injury and was bitten during sleep . Of the children 2 were apparently bitten without provocation, while a 5-year-old boy was bitten when the family dog was disturbed while eating . RESULTS: All wounds were explored, irrigated and debrided . There was no involvement of the testes or spermatic cord . Each wound was closed primarily and 5 healed without sequelae . The spinal cord injured man had partial dehiscence of the incision and in another man superficial hematoma required drainage . Each patient received antibiotics and tetanus prophylaxis but none required rabies inoculation . CONCLUSIONS: Although there are reports of devastating scrotal injuries from dog bites, most such wounds may be treated by careful inspection for intrascrotal injuries followed by debridement and closure . Antimicrobial prophylaxis should be administered, as for any bite wound. Eur J Pharm Biopharm, 2000 Jul, 50(1), 83 - 99 Local delivery of antimicrobial agents for the treatment of periodontal diseases; Schwach-Abdellaoui K et al.; Periodontitis is an inflammatory disease of the supporting tissues of the teeth caused by groups of specific microorganisms . Aggressive forms of periodontitis can be localized or generalized . The concept that localized problem sites may be treated by local drug delivery appears attractive as the antimicrobial agent is delivered within periodontal pockets and the therapy is targeted on specific pathogenic microorganisms . Local delivery of antimicrobial agents using controlled release systems should be considered as adjunctive to mechanical debridement for the treatment of localized forms of periodontal destruction . This article reviews various types of delivery systems evaluated in practical periodontal therapy . Despite the large number of studies showing an enhanced effectiveness of local antibiotherapy, there are insufficient comparative data to support any of the local delivery system. Biochem J, 2000 Jun 15, 348 Pt 3, 649 - 56 Defensin-like peptide-2 from platypus venom: member of a class of peptides with a distinct structural fold; Torres AM et al.; The venom of the male Australian duck-billed platypus contains a family of four polypeptides of appox . 5 kDa, which are referred to as defensin-like peptides (DLPs) . They are unique in that their amino acid sequences have no significant similarities to those of any known peptides; however, the tertiary structure of one of them, DLP-1, has recently been shown to be similar to beta-defensin-12 and to the sodium neurotoxin peptide ShI (Stichodactyla helianthus neurotoxin I) . Although DLPs are the major peptides in the platypus venom, little is known about their biological roles . In this study, we determined the three-dimensional structure of DLP-2 by NMR spectroscopy, with the aim of gaining insights into the natural function of the DLPs in platypus venom . The DLP-2 structure was found to incorporate a short helix that spans residues 9-12, and an antiparallel beta-sheet defined by residues 15-18 and 37-40 . The overall fold and cysteine-pairing pattern of DLP-2 were found to be similar to those of DLP-1, and hence beta-defensin-12; however, the sequence similarities between the three molecules are relatively small . The distinct structural fold of the DLP-1, DLP-2, and beta-defensin-12 is based upon several key residues that include six cysteines . DLP-3 and DLP-4 are also likely to be folded similarly since they have high sequence similarity with DLP-2 . The DLPs, and beta-defensin-12 may thus be grouped together into a class of polypeptide molecules which have a common or very similar global fold . The fact that the DLPs did not display antimicrobial, myotoxic, or cell-growth-promoting activities implies that the nature of the side chains in this group of peptides is likely to play an important role in defining the biological function(s). J Infect Dis, 2000 Jun, 181 Suppl 3, S582 - 4 Collaborative multidisciplinary workshop report: clinical antimicrobial trials for primary and secondary prevention of atherosclerotic cardiovascular disease; Rosen H et al.; The task assigned to the working group on Clinical Antimicrobial Trials for Primary and/or Secondary Prevention of Atherosclerotic Cardiovascular Disease was to evaluate the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials . In addition, the working group was to define the role of collaboration in answering research questions. J Infect Dis, 2000 Jun, 181 Suppl 3, S514 - 8 Antibiotics effects in a rabbit model of Chlamydia pneumoniae-induced atherosclerosis; Fong IW; The association of Chlamydia pneumoniae infection with the complications of atherosclerosis, cardiovascular disease, and stroke are well established . C . pneumoniae infection of New Zealand White rabbit respiratory tract can result in early changes of atherosclerosis of the aorta that are not produced by sham infection or by Mycoplasma pneumoniae (which result in similar lung pathology) . Early institution of antimicrobials with antichlamydial activity (azithromycin, clarithromycin, moxifloxacin, and doxycycline) within 5 days of infection can largely prevent the aortic lesions (75%-85% efficacy) . Early treatment is also effective in suppressing the IgG antibody response to C . pneumoniae . However, delayed treatment (6 weeks after infection) with azithromycin was ineffective in aborting vascular changes but clarithromycin was partially effective (62.5% reduction) . These studies support but do not prove that C . pneumoniae can cause atherosclerosis . Antibiotics are potentially useful in this model, but the optimum dose and duration of therapy or use of combination of agents remain to be determined. J Infect Dis, 2000 Jun, 181 Suppl 3, S456 - 9 Potential for antimicrobial resistance in Chlamydia pneumoniae; Stamm WE; Antimicrobial resistance has not yet been described in wild type Chlamydia pneumoniae isolates, nor has selective emergence of resistance in the laboratory after exposure to subinhibitory concentrations of antibiotic . However, few clinical isolates have been tested for resistance, especially strains with resistance phenotypes (i.e., those associated with clinical failure or persistence) . More widespread testing of such strains is needed . Further understanding of antimicrobial resistance in chlamydiae would benefit from the development of standardized methods . Further, more physiologic testing methodologies that more closely mimic the chronic intracellular infection usually being treated in vivo would be of value . Animal models demonstrate persistence of C . pneumoniae after antimicrobial therapy and could be used to better define the clinical correlates of in vitro testing. Vet Rec, 2000 May 6, 146(19), 545 - 50 Cost-effective antimicrobial drug selection for the management and control of respiratory disease in European cattle; Barrett DC; Respiratory disease in growing cattle has both animal welfare and economic implications, but the use of antimicrobial drugs to treat and control it is under public scrutiny owing to concerns that their use in food-producing animals may be detrimental to human health . This paper outlines criteria for the selection of appropriate and cost-effective drugs, based on good dinical practice and sound economic principles . It also suggests that these principles should be integrated into quality assurance schemes, and that the monitoring of antimicrobial resistance patterns among known bacterial respiratory pathogens should be improved. Phytomedicine, 2000 Apr, 7(2), 167 - 72 In vitro antimicrobial activity of six medicinal plants traditionally used for the treatment of dysentery and diarrhoea in Democratic Republic of Congo (DRC); Otshudi AL et al.; Twenty-four crude extracts derived from six medicinal plants highly valued as antidiarrhoeal agents in Congolese folk medicine were screened for antimicrobial activity against several enteric pathogens . The results of this study indicated that the methanolic and aqueous extracts derived from three of them (Roureopsis obliquifoliolata, Epinetrum villosum and Cissus rubiginosa) possessed prominent antibacterial activity, therefore supporting the ethnomedical uses of these species . In addition, phytochemical analysis of these medicinal plants showed that 1/6 plant sample contained alkaloids, 6/6 triterpenes and/or sterols, 4/6 flavonoids, 3/6 tannins and 5/6 saponins . Anthraquinones were not detected in any of these plants. J Ethnopharmacol, 2000 Jun, 70(3), 281 - 300 Traditional herbal drugs of southern Uganda, I; Hamill FA et al.; One-hundred four plant species used medicinally by herbalists from three southern Ugandan tribes were collected and identified . The collection includes a large portion of the materia medica of the Abayanda of the southwest region, as well as species used by herbalists of the Baganda and Bakiga Tribes . Literature searches were performed in preparation for further collections, and for collaborative laboratory validation of in vitro antimicrobial activity . Literature data provide support for ethnomedical claims for a number of species used in Uganda for disease treatment. J Ethnopharmacol, 2000 Jun, 70(3), 197 - 203 Oldenlandia affinis (R&S) DC . A plant containing uteroactive peptides used in African traditional medicine; Gran L et al.; A review of the geographical distribution, clinical use, biological activity and phytochemistry of Oldenlandia affinis (R&S) DC . is presented . During an inventory of medicinal plants in northern Congo/Brazzaville and south-western Central African Republic in 1962, 196 different species were registered, one of which was O . affinis used for the facilitation of childbirth . A medical team working in Luluabourg (Kananga) in Congo during the troubled period in 1960, discovered also the traditional use of the same plant as an oxitocic agent during labour . The plant was collected and the uterotonic substances isolated . Cyclic peptides (called Kalata-peptides) were described, and the main peptide, B1, was subjected to pharmacological and chemical investigations . Later the three-dimensional structure of the peptide was determined . Similar cyclic peptides have been isolated also from other plants in the Rubiaceae family like Chassalia pasvifoloia and Psychotria longipes, and from Viola species: Viola tricolor L . and Viola arvensis Murray . Some of these peptides, included Kalata-peptide B1, have been shown to hold antimicrobial activity . They have recently been synthesized, and they may represent a starting point for the design of new peptide antibiotics. J Antimicrob Chemother, 2000 Jun, 45(6), 913 - 7 Trends in hospital antimicrobial prescribing after 9 years of stewardship; Gould IM et al.; Trends in antibiotic prescribing in Grampian have been monitored prospectively for 11 years from 1986 using computerized ward stock lists and laboratory data relating to all in-patient and out-patient treatments in all Grampian hospitals . The main outcome measures were the number of antibiotics available for routine and restricted use, annual expenditure and defined daily doses (DDDs) of high expenditure antimicrobial agents . An antibiotic committee introduced a policy and formulary in the third year of the study which has had only limited success in controlling prescribing . This report updates the audit from 1992/3 to 1996/7 . During this period 22 new antibiotics were considered for inclusion in the hospital formulary . Seventeen, including seven antiretroviral agents, were incorporated, all for restricted use only . Despite this, expenditure on antibiotics has more than trebled since 1986/7 and increased 50% since 1992/3, two-thirds of the latter increase being due to the use of new drugs, namely anti-HIV drugs, lipid amphotericin derivatives and teicoplanin . Big increases in the use of co-amoxiclav, acyclovir, ciprofloxacin and cefotaxime account for the remainder of the increased expenditure . There was an overall increase of 16.9% in DDDs between 1992/3 and 96/7 to 424.0 DDDs/1000 patient days (393.4 DDDs for antibacterials) . These findings highlight the current difficulty in controlling prescribing budgets, the increasing use of antibiotics and the consequent increase of antimicrobial-resistant microorganisms. J Antimicrob Chemother, 2000 Jun, 45(6), 797 - 802 Activity of linezolid against Gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors; Fines M et al.; Linezolid belongs to a new class of antimicrobials, the oxazolidinones, that act by inhibiting protein synthesis . To detect cross-resistance with other inhibitors of protein synthesis (chloramphenicol, macrolides, lincosamides, streptogramins, aminoglycosides and tetracyclines), the in vitro activity of linezolid was determined against isolates harbouring known genes conferring resistance to these antimicrobials . Neither the presence of modifying enzymes (LinA, LinA', LinB, Vgb, Vat, SatA, ANT(4') (4")-I, AAC(6')-APH(2"), APHA-3 and Cat), nor the presence of an efflux mechanism (MsrA, MefE, MefA, MreA, Vga, TetK and TeL), nor the modification or protection of antimicrobial target (because of ribosomal methylases or TetM and TetO) affected linezolid activity as demonstrated by similar in vitro activity against resistant isolates and sensitive control isolates. Am J Respir Cell Mol Biol, 2000 Jun, 22(6), 665 - 71 The lactoperoxidase system functions in bacterial clearance of airways; Gerson C et al.; Airway mucus is a complex mixture of secretory products that provides a multifaceted defense against pulmonary infection . Mucus contains antimicrobial peptides (e.g., defensins) and enzymes (e.g., lysozyme) although the contribution of these to airway sterility has not been tested in vivo . We have previously shown that an enzymatically active, heme-containing peroxidase comprises 1% of the soluble protein in sheep airway secretions, and it has been hypothesized that this airway peroxidase may function as a biocidal system . In this study, we show that sheep airway peroxidase is identical to milk lactoperoxidase (LPO) and that sheep airway secretions contain thiocyanate (SCN(-)) at concentrations necessary and sufficient for a functional peroxidase system that can protect against infection . We also show that airway LPO, like milk LPO, produces the biocidal compound hypothiocyanite (OSCN(-)) in vitro . Finally, we show that in vivo inhibition of airway LPO in sheep leads to a significant decrease in bacterial clearance from the airways . The data suggest that the LPO system is a major contributor to airway defenses . This discovery may have significant implications for chronic airway colonization seen in respiratory diseases such as cystic fibrosis. Am J Physiol Cell Physiol, 2000 Jun, 278(6), C1063 - 87 Properties of cytotoxic peptide-formed ion channels; Kourie JI et al.; Cytotoxic peptides are relatively small cationic molecules such as those found 1) in venoms, e.g., melittin in bee, scorpion toxins in scorpion, pilosulin 1 in jumper ant, and lycotoxin I and II in wolf spider; 2) in skin secretions (e.g., magainin I and II from Xenopus laevis, dermaseptin from frog, antimicrobials from carp) and cells of the immune system (e.g., insect, scorpion, and mammalian defensins and cryptdins); 3) as autocytotoxicity peptides, e.g., amylin cytotoxic to pancreatic beta-cells, prion peptide fragment 106-126 {PrP-(106-126)}, and amyloid beta-protein (AbetaP) cytotoxic to neurons; and 4) as designed synthetic peptides based on the sequences and properties of naturally occurring cytotoxic peptides . The small cytotoxic peptides are composed of beta-sheets, e.g., mammalian defensins, AbetaP, amylin, and PrP-(106-126), whereas the larger cytotoxic peptides have several domains composed of both alpha-helices and beta-sheets stabilized by cysteine bonds, e.g., scorpion toxins, scorpion, and insect defensins . Electrophysiological and molecular biology techniques indicate that these structures modify cell membranes via 1) interaction with intrinsic ion transport proteins and/or 2) formation of ion channels . These two nonexclusive mechanisms of action lead to changes in second messenger systems that further augment the abnormal electrical activity and distortion of the signal transduction causing cell death. In Vivo, 2000 Mar-Apr, 14(2), 351 - 5 Antimicrobial and radical modulation activity of AV-07, a poly-herbal formula; Satoh K et al.; An extract of AV-07 was investigated for various biological activities . Pretreatment of mice with the AV-07 extract significantly protected them from lethal infection with E . coli . ESR spectroscopy showed that the extract produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate, suggesting its pro-oxidant action at higher concentrations . The extract effectively scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction and hydroxyl radical, produced by Fenton reaction . These data demonstrate that AV-07 extract contains various bioactive substances, suggesting its medicinal efficacy. Curr Opin Pediatr, 2000 Jun, 12(3), 187 - 93 Current concepts on pulmonary host defense mechanisms in children; Wilmott RW et al.; The respiratory tract is exposed continuously to noxious agents, microbial organisms, particles, and allergens . It has therefore evolved both innate and specific defense mechanisms . The innate host defense mechanisms include components such as collectins, beta-defensins, lactoferrin, and complement, all of which have an important role in modulating the immune response . Immune protection of the lungs by specific antibody is reviewed . The airways are protected by alveolar macrophages, neutrophils, and lymphocytes, and their origins, regulation, functions, and antimicrobial activity are summarized . Antimicrobial peptides and immune-modulating peptides are likely to have a significant therapeutic role for infection and inflammation in the respiratory tract. Inflamm Bowel Dis, 2000 May, 6(2), 116 - 22 Bacterial regulation of intestinal immune responses; MacDonald TT et al.; If we understand pathological processess within the alimentary tract, it is apparent that the fundamental aspects of microbe-host interactions need to be examined in greater detail . Pathogenic bacteria have evolved strategies to alter and subvert the function of T cels and phagocytes in the gut wall, and exploiting these molecules may lead to new treatments for chronic inflammatory bowel diseases . The adaptation of microbes to their host must involve microbe-mediated interference of the host innate immune response . The recent demonstration that nonpathogenic E . coli have a beneficial effect in ulcerative colitis further supports the notion that normal flora may alter the expression of the innate immune receptors or recognize alternative receptors compared with pathogenic variants . Such differences may conceivably lead to beneficial and protective alterations to the host through cytokine and antimicrobial peptide expression . Perhaps the contact point between microbes and host cells lies with the pattern-recognition receptors such as TLRs . However, although much light has been shed on the downstream consequences of TLR activation, many more questions remain unsolved . For example, little is known about the expression profiles of the different TLRs throughout the gastrointestinal tract . Additionally, ambiguities remain over the natural ligands for TLRs . The discovery that the Drosophila Toll receptor acts downstream of the pathogen recognition event suggests that there are many more twists and turns to be revealed in the story of host-microbe interactions in the gastrointestinal tract. Lancet, 2000 May 20, 355(9217), 1813 - 7 Use of antibiotics in penetrating craniocerebral injuries . "Infection in Neurosurgery" Working Party of British Society for Antimicrobial Chemotherapy; Bayston R et al.; The Working Party was instituted to investigate the rationale of prophylactic and therapeutic antibiotic use in penetrating craniocerebral injuries (PCCI), and to make recommendations for current practice . A systematic review of papers on civilian and military PCCI over the past 25 and 50 years, respectively, was done via electronic databases and secondary sources, and data were evaluated . Guidelines on the removal of indriven bone or metal fragments only if further neural damage can be avoided were supported . However, no publications were identified where the data on infection or its treatment and prevention were complete or satisfactorily derived, and no controlled trials have been published . All studies were retrospective or anecdotal . Working Party recommendations are based on the data available and the professional experience and knowledge of the members . Broad-spectrum antibiotic prophylaxis is recommended for both military and civilian PCCI, Including those due to sports or recreational injuries. Cornea, 2000 May, 19(3), 274 - 7 Tetracyclines and the treatment of corneal stromal ulceration: a review; Ralph RA; PURPOSE: To demonstrate the potential value of tetracyclines in the treatment of corneal ulceration after moderate to severe ocular chemical injuries . METHODS: Review of published materials describing landmarks in the development of tetracyclines as matrix metalloproteinase inhibitors in ophthalmology and related disciplines . RESULTS: Tetracyclines can protect the cornea against proteolytic degradation after moderate to severe ocular chemical injury . They inhibit matrix metalloproteinases by mechanisms independent of their antimicrobial properties, primarily through restriction of the gene expression of neutrophil collagenase and epithelial gelatinase, suppression of alpha1-antitrypsin degradation, and scavenging of reactive oxygen species . CONCLUSION: Oral tetracyclines can be used along with topical tetracycline preparations and other therapeutic agents to inhibit collagenolytic degradation of the cornea after moderate to severe ocular chemical injuries. J Inorg Biochem, 2000 Apr, 79(1-4), 253 - 9 Controlling gene expression by zinc(II)-macrocyclic tetraamine complexes; Kikuta E et al.; The zinc(II) complexes of 12-membered macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two aryl-methyl group(s) (quinolyl-methyl, naphthyl-methyl, and acridinyl-methyl) selectively bind to thymines in a TATA box of the SV40 early promoter region and thus inhibit the binding of a transcriptional factor, TATA binding protein . These Zn2+-cyclen derivatives also act as inhibitors of DNA-targeted enzymes, type I and type II topoisomerases . They also exhibited strong antimicrobial activities for the gram-positive bacterial strain . These biochemical and biological properties were compared with those of conventionally established AT-recognizing drugs, distamycin A and DAPI . The Zn2+-cyclen complexes are a new type of small molecular, genetic transcriptional regulation factor. J Vet Med B Infect Dis Vet Public Health, 2000 Apr, 47(3), 191 - 6 Antibacterial susceptibility patterns of Pseudomonas strains isolated from chronic canine otitis externa; Martin Barrasa JL et al.; Development of antibiotic resistance in bacteria is a problem of great concern . It is important to establish the convenience of antimicrobial susceptibility tests in animal infections . The aim of this study was to test the susceptibility to antibiotics of Pseudomonas strains isolated from chronic canine otitis externa . We tested 23 strains of Pseudomonas: 19 Ps . aeruginosa, three Ps . fluorescens and one Pseudomonas spp . The most effective antibiotics were tobramycin (100% susceptible), marbofloxacin (91.3%) and ceftazidime (91.3%) . Ticarcillin and gentamicin, commonly used for the treatment of otitis externa also showed good results (susceptibility of strains was 86 and 65.2% respectively) . Lower susceptibility was found using enrofloxacin (52.1%) probably due to its indiscriminate use . We emphasize the need for a rational policy of antibiotic prescribing in order to prevent the selection of resistant strains. Infect Dis Clin North Am, 2000 Jun, 14(2), 449 - 62, x The newer macrolides: azithromycin and clarithromycin; Zuckerman JM; Azithromycin and clarithromycin are two relatively new macrolide antimicrobial agents . Although azithromycin and clarithromycin are structural analogues of erythromycin, they offer distinct advantages in comparison . This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse affects of these antimicrobial agents. Infect Dis Clin North Am, 2000 Jun, 14(2), 391 - 408, ix Antibacterial agents in infections of the central nervous system; Chowdhury MH et al.; Experimental animal models have provided information applicable to antimicrobial therapy of infections of the central nervous system . The efficacy of an antimicrobial agent in the therapy of bacterial meningitis depends on its ability to penetrate the blood-brain barrier, its activity in purulent cerebrospinal fluid, and a demonstration of rapid bactericidal activity against the offending pathogen . The recent emergence of resistant pathogens is challenging the therapy for bacterial meningitis . Various strategies for treating resistant pathogens have been evaluated in experimental animal models . Encouraging results have led to clinical trials to evaluate the efficacy of newer agents, alone or in combination with standard regimens. Infect Dis Clin North Am, 2000 Jun, 14(2), 321 - 39 Topical antibacterial agents; Kaye ET; Topical antibacterial agents occupy an important niche of antimicrobial therapy for both inpatients and outpatients . These agents, including antiseptic and antibiotic preparations, are used for prophylaxis and treatment of infection . Prophylactic uses include application for traumatic and surgical wounds, burns, intravascular catheters, and eradication of S . aureus nasal carriage . Topical antibacterial agents are also used for treatment of primary and secondary pyodermas . Individual antibacterial agents have been reviewed . Of note, despite the widespread use of topical antibacterial agents, further data on which to guide therapy are needed in many instances. Infect Dis Clin North Am, 2000 Jun, 14(2), 293 - 319 Pathogens resistant to antimicrobial agents . Epidemiology, molecular mechanisms, and clinical management; Kaye KS et al.; The emergence of resistance to antimicrobial agents continues to be a major problem in the nosocomial setting and now in nursing homes and the community as well . Bacteria use a variety of strategies to avoid the inhibitory effects of antibiotic agents and have evolved highly efficient means for the dissemination of resistance traits . Control of antibiotic-resistant pathogens provides a major challenge for both the medical community and society in general . To control the emergence of resistant pathogens, CDC and infection control guidelines must be adhered to, and antibiotics must be used more judiciously. Infect Dis Clin North Am, 2000 Jun, 14(2), 281 - 91, vii Pharmacodynamics of antibacterial drugs; Levison ME; Pharmacodynamics of antibacterial agents relates the time course of drug concentration to its antimicrobial effects at the infection site . Antibacterial agents can be divided into three groups based on pharmacodynamic characteristics: agents that exhibit concentration-dependent bactericidal activity over a range of drug concentrations (e.g., aminoglycosides and fluoroquinolones); agents that exhibit time-dependent bactericidal activity that has little relationship to the magnitude of concentration, provided the concentrations are above a minimally effective level (e.g., beta-lactam antibiotics and vancomycin); and agents that exhibit a predominantly bacteriostatic effect . Knowledge of antimicrobial pharmacodynamics provides a rational basis for determining optimal regimens of dosage amounts and length of dosage intervals. Infect Dis Clin North Am, 2000 Jun, 14(2), 265 - 79, vii Principles of selection and use of antibacterial agents . In vitro activity and pharmacology; Hessen MT et al.; The selection of an antimicrobial treatment regimen is based on many factors, including the nature of the infection, the identity and susceptibility pattern of the infecting organisms, and the pharmacokinetics and pharmacodynamics of the antibacterial drugs . This article discusses principles of susceptibility testing, pharmacology, and monitoring of therapy. Helicobacter, 2000, 5 Suppl 1, S23 - 6; discussion S27-31 Challenges to therapy in the future; O'Morain C et al.; Quadruple therapy (with a proton pump inhibitor (PPI), metronidazole, tetracycline and bismuth) is generally reserved for second-line treatment; however, studies using this regimen for 7 days have found it to be effective even in metronidazole-resistant strains . Resistance is an ongoing problem with antimicrobial therapy but considerable progress has now been made into understanding the underlying genetic mechanisms of this process . Metronidazole resistance in Europe is usually in the range of 20-30% of strains but may be as high as 70% in some countries . One genetic mechanism involved is thought to be a mutation of the rdxA gene . Macrolide resistance appears to be on the increase in Europe, varying from 1% in some countries to 13% in others . The genetic mechanism involved has been shown to be a point mutation of a ribosomal RNA . Amoxicillin resistance is an emerging problem that has an adverse effect on eradication rates in clinical practice . Resistance has been shown to be caused by the absence of one of the four binding proteins in the cell wall . Few novel antibiotics have been developed for use in eradication therapy, although rifabutin, secnidazole and furazolidone have shown some success as part of combination therapy . Alternative therapies that have been tested include mucosal protective agents which have been used in place of a PPI in some eradication regimens with some success, and the somatostatin analog, octreotide, that has been used as part of quadruple therapy in place of a PPI and produced eradication rates of approximately 88% . The ultimate challenge is still to develop a safe and effective vaccine against Helicobacter pylori . Current and future research will also focus on identifying genetic targets for therapy, adhesion molecule analogs to prevent binding of the bacterium, and urease inhibitors . The current triple therapy treatment options available for the eradication of Helicobacter pylori infection are over 90% effective in susceptible organisms and there are very few medical conditions to which we can offer such efficacious treatment . Unfortunately, the recommendations made at consensus conferences are not always put into practice and physicians in primary care may be unaware of the true efficacy of eradication therapy . Treatment is very simple: three drugs, twice a day for 1 week . The main focus for both primary care physicians and gastroenterologists should be to reinforce the need for patient compliance, otherwise we will see an increase in antibiotic resistance . Patients should be prewarned that they may experience some mild side effects and should be encouraged to complete the course of treatment . The real challenge for the future will be the management of patients who do not respond to first-line treatment . This paper will focus on potential problems with therapy, such as antibiotic resistance, and possible future solutions, such as novel antibiotics and vaccines. Helicobacter, 2000, 5 Suppl 1, S17 - 21; discussion S27-31 Where are We with current therapy? Sung JJ. Despite intensive research and widely publicized recommendations from consensus meetings in different continents, the public and primary care physicians are relatively slow in picking up the impact of Helicobacter pylori infection and identifying optimal therapies . The treatment of H . pylori infection has evolved from bismuth-containing regimens, 2-week proton pump inhibitor (PPI)-dual therapies, and now, the widely accepted PPI/ranitidine bismuth citrate (RBC) single week triple therapies . There is a wealth of evidence showing that these regimens are highly efficacious and well tolerated by patients . The MACH-2 studies have confirmed that the addition of a PPI to two antimicrobials has significantly improved the cure rate of H . pylori infection and reduced the impact of antimicrobial resistance . Attempts to use shorter regimens ranging from 1 to 3 days should be resisted because of their unacceptably low therapeutic efficacy . In the United States, there are some indications that 10-14 days of treatment may be required . While the first-line therapies for H . pylori infection is well established, we are still struggling with the choice of optimal regimen in retreatment after the first attempt fails . Quadruple therapy combining PPI with bismuth, metronidazole and tetracycline has achieved a respectable success of around 85% . Switching between metronidazole and clarithromycin seems to be a sensible strategy as these two are the most effective anti-Helicobacter agents . Changing between PPI and RBC in the triple therapy would not make much difference without replacing some of the antimicrobials . Rifabutin-containing regimens and high-dose PPI-amoxicillin dual therapy deserve more studies with large-scale studies . Data on anti-Helicobacter therapy for children are few . Most studies based on bismuth derivatives in combination with amoxicillin or tinidazole and were limited by the small number of cases . Recent studies showed 1-week bismuth-based triple therapy and 2-week PPI-based triple therapy are highly efficacious . Reinfection in children > 5 years of age after successful cure is rare . It is worthwhile to refine the optimal therapy for children as the treatment of this group would, theoretically, prevent the development gastric cancer in the long term. Gynecol Obstet Invest, 2000, 49(4), 261 - 5 Use of chlorhexidine-releasing nylon fibres to reduce device-related uterine infections; Gard PR et al.; Implantation of intrauterine devices (IUDs) is associated with an increased incidence of uterine infection, probably as a result of vaginal bacteria entering the uterus at the time of insertion . To reduce the incidence of IUD-related infections, the incorporation of antimicrobial agents into the tail of the device was studied . Chlorhexidine was shown to be released from within nylon hollow fibres at a rate of approximately 114 microg x day(-1) for 10 days . This rate of release was sufficient to exhibit a biocidal effect on bacteria embedded within a mucus gel in vitro . When these devices were implanted transcervically into the guinea-pig uterus they significantly reduced the extent of uterine bacterial contamination within 24 h . These findings indicate that chlorhexidine-releasing devices are potentially useful in the reduction of device-related infections . Curr Microbiol, 2000 Jun, 40(6), 392 - 7 Effect of antimicrobial agents on livestock waste emissions; Varel VH et al.; Various antimicrobial agents were evaluated with the purpose of reducing the microbial fermentation in stored cattle waste and the resulting odor emissions . Duplicate sealed 2-L flasks with 500 ml waste slurry, with and without antimicrobial inhibitors, were used to measure the production of short-chain volatile fatty acids, lactate, and total fermentation gas over 27-30 days . A combination of chlorhexidine diacetate (2 mM), iodoacetate (2 mM), and alpha-pinene (3.8 mM) reduced gas production 80% (1000 ml to 200 ml) and total volatile fatty acid production 50% (145 mM to 72 mM) . Pinene had little antimicrobial effect; rather, it served as an effective masking agent, giving the waste a less offensive odor . A combination of chlorhexidine diacetate and the deaminase inhibitor, diphenyliodonium chloride (1.3 mM) had a similar effect in reducing short-chain volatile fatty acid production (145 mM to 80 mM) . It is concluded that a combination of antimicrobial agents may be useful in controlling odor emissions and conserving organic matter in livestock wastes, therefore providing a potentially more useful byproduct waste when used as plant fertilizer. J Biol Chem, 2000 Oct 20, 275(42), 32721 - 7 Gram-negative bacteria-binding protein, a pattern recognition receptor for lipopolysaccharide and beta-1,3-glucan that mediates the signaling for the induction of innate immune genes in Drosophila melanogaster cells; Kim YS et al.; Pattern recognition receptors, non-clonal immune proteins recognizing common microbial components, are critical for non-self recognition and the subsequent induction of Rel/NF-kappaB-controlled innate immune genes . However, the molecular identities of such receptors are still obscure . Here, we present data showing that Drosophila possesses at least three cDNAs encoding members of the Gram-negative bacteria-binding protein (DGNBP) family, one of which, DGNBP-1, has been characterized . Western blot, flow cytometric, and confocal laser microscopic analyses demonstrate that DGNBP-1 exists in both a soluble and a glycosylphosphatidylinositol-anchored membrane form in culture medium supernatant and on Drosophila immunocompetent cells, respectively . DGNBP-1 has a high affinity to microbial immune elicitors such as lipopolysaccharide (LPS) and beta-1,3-glucan whereas no binding affinity is detected with peptidoglycan, beta-1,4-glucan, or chitin . Importantly, the overexpression of DGNBP-1 in Drosophila immunocompetent cells enhances LPS- and beta-1,3-glucan-induced innate immune gene (NF-kappaB-dependent antimicrobial peptide gene) expression, which can be specifically blocked by pretreatment with anti-DGNBP-1 antibody . These results suggest that DGNBP-1 functions as a pattern recognition receptor for LPS from Gram-negative bacteria and beta-1, 3-glucan from fungi and plays an important role in non-self recognition and the subsequent immune signal transmission for the induction of antimicrobial peptide genes in the Drosophila innate immune system. J Biol Chem, 2000 Aug 11, 275(32), 24490 - 9 Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth; Liu C et al.; Peptidoglycan recognition protein (PGRP) is conserved from insects to mammals . In insects, PGRP recognizes bacterial cell wall peptidoglycan (PGN) and activates prophenoloxidase cascade, a part of the insect antimicrobial defense system . Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown . However, it was suggested that an identical protein (Tag7) was a tumor necrosis factor-like cytokine . Therefore, the aim of this study was to identify the function of PGRP in mammals . Mouse PGRP bound to PGN with fast kinetics and nanomolar affinity (K(d) = 13 nm) . The binding was specific for polymeric PGN or Gram-positive bacteria with unmodified PGN, and PGRP did not bind to other cell wall components or Gram-negative bacteria . PGRP mRNA and protein were expressed in neutrophils and bone marrow cells, but not in spleen cells, mononuclear cells, T or B lymphocytes, NK cells, thymocytes, monocytes, and macrophages . PGRP was not a PGN-lytic or a bacteriolytic enzyme, but it inhibited the growth of Gram-positive but not Gram-negative bacteria . PGRP inhibited phagocytosis of Gram-positive bacteria by macrophages, induction of oxidative burst by Gram-positive bacteria in neutrophils, and induction of cytokine production by PGN in macrophages . PGRP had no tumor necrosis factor-like cytotoxicity for mammalian cells, and it was not chemotactic on its own or in combination with PGN . Therefore, mammalian PGRP binds to PGN and Gram-positive bacteria with nanomolar affinity, is expressed in neutrophils, and inhibits growth of bacteria. Curr Opin Chem Biol, 2000 Jun, 4(3), 310 - 7 Lantibiotics and microcins: polypeptides with unusual chemical diversity; Jack RW et al.; Bacterial-derived antimicrobial polypeptides enjoy a large degree of structural and chemical diversity . Two well-studied examples of such polypeptides are the lanthionine-containing lantibiotics produced by a variety of Gram-positive bacteria, and their Gram-negative counterparts, the microcins . Both groups are produced as gene-encoded precursor peptides and undergo post-translational modification to generate the active moieties . Structure elucidation of novel lantibiotics and microcins has recently uncovered further novel structural and chemical features and, combined with the generation of analogue peptides by genetic manipulation, new insights into structure-function relationships have been gained . Furthermore, study of the mode of action of the lantibiotics nisin and mersacidin has revealed their use of a 'docking molecule' in the target cell to facilitate their biological activities . Meanwhile, in vitro studies with microcin B17 have helped to uncover the molecular mechanisms by which post-translational modification results in the formation of heterocyclic oxazole and thiazole rings . From a practical standpoint, both groups of polypeptides represent new lead structures for future development of antimicrobial agents, whilst the identification of the 'docking molecules' represents a step forward in the search for novel targets for future antibiosis. Aviakosm Ekolog Med, 2000, 34(2), 66 - 70 {The use of antimicrobial stabilizers in biochemical research}; Pishak VP et al.; The ability of highly active antimicrobial biochemical stabilizers to sustain samples (T = 4 degrees C to 8 degrees C) till biochemical analysis in 20-50 days was tested . A new generation of delayed biochemical assays with the use of these stabilizers can be invoked in metabolic studies of cosmonauts and aviators, personnel of atomic submarines, pole explorers and other occupational groups. Endod Dent Traumatol, 1999 Dec, 15(6), 278 - 83 The diagnostic accuracy of microbiologic root canal sampling and the influence of antimicrobial dressings; Reit C et al.; The routine approach to endodontic treatment of teeth with apical periodontitis often involves an interappointment dressing with calcium hydroxide . However, investigations have demonstrated a negative influence of calcium hydroxide on the accuracy of microbiological root canal sampling (MRS) . The aim of the present study was to investigate whether the use of a fluid dressing like 5% iodine potassium iodide (IPI) would increase the accuracy of MRS . Following instrumentation of 50 teeth with radiographically verified apical periodontitis the root canals received IPI as an intracanal dressing . One week after closure canals were sampled, "test sample" (TS), and then left filled with sampling fluid and temporarily scaled . Seven days later a "gold standard" (GS) sample was obtained . Bacteria were recovered in 22 teeth (44%) in TS as well as in GS . Fifteen teeth (30%) were positive for growth in both samples . Using the detection level "very sparse growth" of microbes the sensitivity and specificity of MRS reached 68% and 75%, respectively . In an earlier study, following the same experimental protocol, but with calcium hydroxide as intracanal dressing, the corresponding values were 33% and 81% . In 25% of these cases bacteria persisted in the canals . As compared to calcium hydroxide, the use of IPI resulted in improved test accuracy, but loss of antibacterial capacity . Conclusively, intracanal dressings seem to vary in their influence on the microbiologic test performance as well as in their antibacterial efficacy . In a clinical situation the choice of interappointment dressing should include consideration of these potentially conflicting properties. J Control Release, 2000 Jul 3, 67(2-3), 293 - 307 In vitro studies and modeling of a controlled-release device for root canal therapy; Huang J et al.; Endodontic disease is caused primarily by bacteria that interact with periradicular host tissues . Therefore, treatment of endodontic disease aims at the exclusion of bacteria from the root canal system . This work focused on in vitro studies and modeling of a controlled-release device for delivering antimicrobial agents in root canals . A cylindrical, needle-shaped device was prepared consisting of a matrix core and a polymer coating, loaded with 30-45% chlorhexidine (CHX) . The composition of the core, a blend of water-permeable polymers, and the thickness of the coating were tailored to impart various release rates . A relatively steady release rate for over 40 days after an initial burst was achieved using a formulation for long-term release, which is desirable for establishing and maintaining the necessary therapeutic levels . Mathematical models were developed for both in vitro and in vivo drug release into a liquid of limited volume, taking into account a moving boundary of the dispersed drug and a time-dependent boundary condition . A concentration-dependent effective diffusion coefficient was used to count increased porosity as the solid drug had dissolved . The finite element method and computer programs were applied to solve the differential equations and predict the in vitro and in vivo release kinetics . The model prediction agreed well with the in vitro experimental data and provided guidance for designing the device for in vivo release in root canals . The result of in vitro antimicrobial tests, performed using a bovine tooth model, suggested that the device was effective in reducing growth of microbes. Biochim Biophys Acta, 2000 May 23, 1478(2), 289 - 99 Dissecting the nucleotide binding properties of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase with fluorescent 3'(2)'-o-anthraniloyladenosine 5'-triphosphate; Shi G et al.; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7, 8-dihydropterin, the first reaction in the folate biosynthetic pathway . Like other enzymes in the folate pathway, HPPK is an ideal target for development of antimicrobial agents because the enzyme is essential for microorganisms but is absent from humans and animals . Using 3'(2')-o-anthraniloyladenosine 5'-triphosphate as a fluorescent probe, a fluorometric competitive binding assay has been developed for measuring the dissociation constants of various compounds that bind to the ATP site of HPPK . The fluorometric assay has been used to determine the nucleotide specificity and dissect the energetics of the binding of MgATP . The order of affinity of various nucleoside triphosphates for HPPK is MgATP>MgGTP>MgITP>MgXTP approximately MgUTP approximately MgCTP . The affinity of MgATP for HPPK (K(d)=2.6+/-0.06 microM) is 260-fold higher than that of MgGTP and more than 1000-fold higher than those of the other nucleoside triphosphates, indicating that HPPK is highly specific with respect to the base moiety of the nucleotide . The affinity of ATP for HPPK in the presence of Mg(2+) is 15 times that in the absence of Mg(2+), indicating that the metal ion is important for the binding of the nucleotide . Removal of the gamma-phosphate from MgATP reduces its affinity for HPPK by a factor of approximately 21 . The affinity of AMP for HPPK is about one third that of ADP and almost the same as that of adenosine . The result suggests that among the three phosphoryl groups of MgATP, the gamma-phosphoryl group is most critical for binding to HPPK and the alpha-phosphoryl group contributes little to the binding of the nucleotide . The affinity of MgATP is 18 times that of MgdATP, indicating that the 2'-hydroxyl group of MgATP is also important for binding . van't Hoff analysis suggests that binding of MgATP is mainly driven by enthalpy at 25 degrees C and the entropy of binding is also in favor of the formation of the HPPK.MgATP complex. Clin Infect Dis, 1999 Apr, 28(4), 778 - 84 Hepatosplenic cat-scratch disease in children: selected clinical features and treatment; Arisoy ES et al.; We reviewed 19 cases of hepatosplenic cat-scratch disease at Texas Children's Hospital (Houston) . The range of the patients' ages was 2 years 4 months to 11 years 8 months . The chief complaint was fever for all patients . The duration of fever before diagnosis was 7 to 56 days (mean, 22 days) . Abdominal pain was present in 13 patients (68%) . Thirteen children were treated with rifampin alone, and three received rifampin therapy plus gentamicin or trimethoprim-sulfamethoxazole . Once rifampin therapy was initiated alone or in combination, improvement was noted within 1 to 5 days (mean, 2.6 days) for patients who had had prolonged fever the duration of which before rifampin therapy averaged 3 weeks . The most common dosage and duration for our patients were 20 mg/{kg x d} every 12 hours and 14 days, respectively . Rifampin should be considered in the initial antimicrobial treatment of hepatosplenic cat-scratch disease. Clin Infect Dis, 1999 Apr, 28(4), 726 - 9 Pneumonia in the elderly: overview of diagnostic and therapeutic approaches; Fein AM; Pneumonia is more frequent in the elderly and results in higher morbidity and mortality . Although the incidence of pneumonia increases with age, from 1 per 1,000 to 12 per 1,000 persons over age 75 years, comorbid medical illnesses and host defense impairments (especially heart disease, chronic obstructive pulmonary disease, and aspiration risk) are independent risk factors . The microbial etiology of pneumonia in the healthy elderly is similar to that in younger patients but shifts toward a more gram-negative and opportunistic flora with increasing age and severity of concomitant medical illness . The choice of antimicrobial therapy must be based on risk stratification (age, medical illnesses, and severity of presentation) . Guidelines based on these principles will be reviewed . Pneumococcal and influenza vaccination reduce the risk of death due to pneumonia and are cost-effective preventative strategies. Eur J Biochem, 2000 Jun, 267(11), 3289 - 300 Membranolytic selectivity of cystine-stabilized cyclic protegrins; Tam JP et al.; To correlate conformational rigidity with membranolytic selectivity of antimicrobial activity and cytotoxicity, we prepared six cyclic analogs of protegrin-1 (PG-1), an 18-residue cationic peptide with a broad-spectrum antimicrobial activity . These cyclic protegrins bear end-to-end peptide bonds together with varying numbers (zero to three) of cross-strand disulfide constraints . The most constrained analog is a cyclic tricystine protegrin (ccPG 3) containing three evenly spaced, parallel disulfide bonds . Antimicrobial assays against 10 organisms in low- and high-salt conditions showed that these cyclic protegrins were broadly active with different antimicrobial profiles against Gram-positive and Gram-negative bacteria, fungi and one tested virus, HIV-1 . Compared to PG-1, the cyclic tricystine ccPG 3 displayed approximately a 10-fold decrease in hemolytic activity against human cells and 6- to 30-fold improvement of membranolytic selectivity against six of the 10 tested organisms . In contrast, {DeltaSS}cPG 8, a cyclic protegrin with no disulfide bond, and {DeltaCys6,15}cPG 5, a cyclic mimic of PG-1 with one disulfide bond, exhibited activity spectra, potency, and cytotoxicity similar to PG-1 . Circular dichroism showed that cyclic protegrins containing with one to three cystine bonds displayed some degree of beta-strand structures in water/trifluoroethanol or phosphate-buffered solutions . Collectively, our results indicate that cyclic structures are useful in the design of antimicrobial peptides and that an increase in the conformational rigidity of protegrins may confer membranolytic selectivity that dissociates antimicrobial activity from hemolytic activity. J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 47 - 9 In vitro activity of gemifloxacin and other antimicrobial agents against isolates of Bordetella pertussis and Bordetella parapertussis; Mortensen JE et al.; We investigated the activity of the novel quinolone agent gemifloxacin (SB-265805) and a panel of comparator agents against Bordetella pertussis and Bordetella parapertussis . Erythromycin, azithromycin, ciprofloxacin and gemifloxacin were consistently active against both species . An azithromycin- and erythromycin-resistant B . pertussis isolate was not resistant to any of the other agents tested (gemifloxacin MIC < or =0.008 mg/L; ciprofloxacin, 0.015 mg/L; ampicillin, 2.0 mg/L; trimethoprim-sulphamethoxazole, 4.0 mg/L) . The potency of ampicillin, azithromycin, erythromycin, ciprofloxacin and trimethoprim-sulphamethoxazole recorded against B . pertussis and B . parapertussis in this study was comparable to that noted in previous studies . However, MICs were generally higher than those noted in other trials; this may reflect the different methods used . Although in vitro data on the potency of gemifloxacin against B . pertussis and B . parapertussis have not previously been reported, these results are comparable to the potency of other quinolones against these pathogens . Should gemifloxacin achieve similar concentrations within the respiratory tract as other quinolones, this, coupled with its high in vitro potency, suggests that gemifloxacin has potential clinical efficacy in pertussis. Infect Control Hosp Epidemiol, 2000 May, 21(5), 347 - 51 SHEA conference on antimicrobial resistance . Society for Healthcare Epidemiology of America; Gerding DN et al.; Antimicrobial resistance is an increasing problem in healthcare institutions and in the community . Public concern about resistance is also increasing . The issue is broad and complex and not readily addressed by government, industry, or professional societies alone . On October 29-30, 1998, 19 representatives of various professional societies and governmental agencies met under the auspices of the Society for Healthcare Epidemiology of America (SHEA) at Brook Lodge Conference Center in Augusta, Michigan . The purpose of the meeting was to discuss the current status of antimicrobial resistance in the United States and Canada, including present society and governmental efforts to address the problem . Representatives exchanged experiences through presentations and discussions on the first day, then on the second day held a brainstorming session to address future needs and priorities in addressing the resistance problem . It was agreed that a national coordinated effort was needed . As part of this national effort, representatives called for the creation of a National Coalition on Antibiotic Resistance (NCAR) to combat antibiotic resistance through education, research, prevention, and advocacy . Priorities for NCAR were focused in four areas: (1) education of the public and professionals; (2) support of basic and applied research; (3) provision of an information resource and clearinghouse; and (4) advocacy initiatives . At the recommendation of the SHEA Board, discussions with the National Foundation for Infectious Diseases for the joint development of NCAR have begun. Ann Otol Rhinol Laryngol, 2000 May, 109(5), 484 - 7 Effects of clarithromycin on rheological properties of nasal mucus in patients with chronic sinusitis; Rhee CS et al.; Macrolide antibiotics have a variety of actions along with antimicrobial action . To determine the effects of oral administration of clarithromycin (CAM) on rheological properties, we measured the spinability, dynamic viscoelasticity, and solid composition of human nasal mucus from 18 patients with chronic sinusitis before and after administration of CAM for 4 weeks . After administration of CAM, the spinability and percent solid composition of nasal mucus increased from 26.5 +/- 12.2 mm to 40.2 +/- 18.7 mm and 7.86% +/- 3.47% to 13.90% +/- 3.67% (p < .05), respectively, whereas the ratio of the viscosity to the elasticity (eta'/G') of nasal mucus after the administration of CAM decreased in all of the mucus samples . These results suggest that treatment with CAM may modulate the rheological properties of nasal mucus in patients with chronic sinusitis. Clin Ther, 2000 Apr, 22(4), 372 - 87; discussion 371 Sparfloxacin: a review; Schentag JJ; BACKGROUND: The continuing increase in the rate of penicillin and cephalosporin resistance among respiratory pathogens and of cross-resistance to macrolide antibiotics has led to the recommendation that fluoroquinolone antibiotics be used to treat high-risk patients with community-acquired pneumonia (CAP) and acute bacterial exacerbations of chronic bronchitis (ABECB) . OBJECTIVE: This review focuses on sparfloxacin, an oral fluoroquinolone, discussing its mechanism of action, activity, pharmacokinetic characteristics, safety, and efficacy in CAP and ABECB . METHODS: Studies were identified by a MEDLINE search of the literature from 1990 to 1999, supplemented by educational materials from conferences and symposia . RESULTS: Sparfloxacin is active against the major respiratory pathogens and against the atypical pathogens in pneumonia that are being reported with increasing frequency . Its long half-life permits once-daily dosing . In large trials in CAP and ABECB in which all isolates were susceptible to both comparators, sparfloxacin was found to have similar efficacy to erythromycin, cefaclor, amoxicillin, ofloxacin, and clarithromycin . Its safety profile is similar to that of the macrolides and other quinolone antimicrobial agents . Photosensitivity, nausea, and diarrhea are the most common adverse events reported in clinical trials of sparfloxacin . Its use is contraindicated in patients with QTc-interval prolongation . CONCLUSION: The increasing prevalence of beta-lactam- and macrolide-resistant bacteria in respiratory infections emphasizes the need for newer agents such as the fluoroquinolones . The choice between agents should be based on activity against the relevant respiratory pathogens in high-risk patients. Mycopathologia, 1999, 146(3), 121 - 6 Antibiotic secondary metabolites of Dichotomomyces cejpii; Pieckova E et al.; Nine fungal strains of Dichotomomyces cejpii were studied for their ability to produce antibiotic metabolites . It was found that they produced secondary exo- and endometabolites with antimicrobial activity against Gram-negative and Gram-positive bacteria, yeasts and moulds and with a toxic effect against animal organs in vitro . Detailed chemical characterization of these active principles need to be carried out. Biochemistry, 2000 May 23, 39(20), 6103 - 14 Cyclization of a cytolytic amphipathic alpha-helical peptide and its diastereomer: effect on structure, interaction with model membranes, and biological function; Oren Z et al.; The amphipathic alpha-helical structure is considered to be a prerequisite for the lytic activity of a large group of cytolytic peptides . However, despite numerous studies on the contribution of various parameters to their structure and activity, the importance of linearity has not been examined . In the present study we functionally and structurally characterized a linear amphipathic alpha-helical peptide (wt peptide), its diastereomer, and cyclic analogues of both . Using analogues with the same sequence of hydrophobic and positively charged amino acids, but with different propensities to form a helical structure, we were able to examine the contribution of linearity to helix formation, bilogical function, and membrane binding and permeation . Importantly, we found that cyclization increases the selectivity between bacteria and human erythrocytes by substantially reducing the hemolytic activity of the cyclic peptides compared with the linear peptides . Moreover, whereas the wt peptide was highly active toward gram(+) bacteria, its cyclic counterpart is active toward both gram(+) and gram(-) bacteria . These findings are correlated with an impaired ability of the cyclic analogues to bind and permeate zwitterionic phospholipid membranes compared with their linear counterparts and an increase in the binding and permeating activity of the cyclic wt peptide toward negatively charged membranes . Furthermore, cyclization abolished the oligomerization of the linear wt peptide in solution and in SDS, suggesting an additional factor that may account for the difference in the spectrum of antibacterial activity between the linear and the cyclic wt peptides . Interestingly, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy revealed that, despite cyclization and incorporation of 33% D-amino acids along the peptide backbone, the membrane environment can impo