J Androl, 2000 Sep-Oct, 21(5), 669 - 75 Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correlation with gram positive bacterial growth and treatment response; Shahed AR et al.; The etiology of chronic pelvic pain syndrome (CPPS)/chronic prostatitis category III remains unknown . Whereas a subset of men respond to antimicrobial therapy, gram positive bacteria isolated from expressed prostatic secretions (EPS) are often considered to be commensal rather than pathogenic . We wished to study oxidative stress as a marker of tissue injury and response in EPS of men with CPPS to determine whether infection with gram positive bacteria is associated with increased oxidative stress . A total of 300 EPS specimens from 100 men with CPPS were collected for microscopy, culture, and biochemical and molecular assays . Oxidant injury was measured by 8-isoprostane F2alpha (IsoP) levels and total antioxidant capacity as Trolox equivalents . Total RNA from EPS was used for gene expression of heme oxygenase-1 (HO-1) and granzyme B . The only bacteria found in EPS were gram positive . For our analysis, these men were classified as having chronic bacterial prostatitis (category II) . IsoP levels (pg/mL) were highest in men with category II prostatitis (7315 +/- 1428) followed by nonbacterial prostatitis (category IIIa, 2043 +/- 561), prostatodynia (category IIIb, 319 +/- 81), and asymptomatic controls (298 +/- 99) . IsoP levels decreased significantly after successful treatment with antibiotics or an antioxidant supplement (Prosta-Q) . Antioxidant capacity was detected in 11 out of 18, 4 out of 16, and 1 out of 16 men tested with category II, IIIa, and IIIb prostatitis, respectively . No correlation was observed between IsoP levels and the number of white blood cells in EPS . HO-1 and granzyme B expression was highest in men with category II prostatitis than in men with either category III prostatitis or asymptomatic controls . On the basis of elevated oxidative stress, clinical response to antibiotics, and post-treatment reduction in oxidative stress, we conclude that gram positive bacteria in some men with CPPS may be pathogens . It is speculated that oxidative stress may be a key pathway in some men with CPPS that can be targeted with antioxidant therapy. Curr Pharm Des, 2000 Nov, 6(16), 1625 - 9 Regional pharmacokinetics of orally administered PET tracers; Fischman AJ et al.; Positron emission tomography (PET) is currently the most useful imaging technique for noninvasive measurement of drug pharmacokinetics regionally in a variety of tissues . Over the past decade, PET measurements have provided many critical insights about the tissue distribution of several classes of drugs; neuroleptics, antimicrobials, antineoplastics, etc . PET measurements can be performed after any route of drug administration, intravenous, inhalation or oral, however, intravenously administered drugs have been the most extensively evaluated . Studies of orally administered drugs are clearly of great interest; however, formulation issues have precluded widespread applications in these areas . In this report, we discuss the unique problems associated with studying orally administered drugs and review the results of recent studies performed in our laboratory. Curr Pharm Des, 2000 Oct, 6(15), 1537 - 44 Antibiotic-resistant H . pylori infection and its treatment; Graham DY et al.; Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients . The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later . Antimicrobial resistance is largely responsible for treatment failures . Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression . Clarithromycin is the most effective antibiotic against H . pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin . The choice of therapy should be based on local susceptibility patterns . Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole) . Where available, treatment failure should prompt endoscopy and culture and susceptibility testing . Overall, higher doses and longer durations of treatment result in the best cure rates . When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used . Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H . pylori. Curr Pharm Des, 2000 Oct, 6(15), 1515 - 29 Strategy for treatment of Helicobacter pylori infection in adults . II . Practical policy in 2000; Nakajima S et al.; The approach to the patient with suspected H . pylori infection consists of an adequate indication to test for the presence of the infection, choice of an appropriate antimicrobial regimen, and education about its use and side effects, followed by post-therapy testing to confirm cure . We review the drugs and regimens for H . pylori eradication and present a strategy for treating the infection . The major factor in choosing an antibiotic regimen is the pattern of antibiotic resistance in the community . Triple therapy with a proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) and two antimicrobials is recommended as the first choice regimen . In regions where metronidazole and clarithromycin resistance are common, initial therapy with quadruple therapy consisting of bismuth, metronidazole, tetracycline, and a PPI is recommended . In general, higher doses and longer durations are associated with better outcomes . For this reason we recommend that the minimum duration of 10 days and we prefer 14 days . The actual choice of the antimicrobial combination will also be influenced by the drugs approved by the local regulatory bodies . Side effects, eradication failure and current as well as future designs of eradication therapies are also discussed. Biochem Biophys Res Commun, 2000 Sep 7, 275(3), 904 - 9 CRAMP analogues having potent antibiotic activity against bacterial, fungal, and tumor cells without hemolytic activity; Shin SY et al.; CRAMP-18 (GEKLKKIGQKIKNFFQKL) is the antibacterial sequence derived from CRMAP, a member of cathelicidin-derived antimicrobial peptides . To develop the novel antibiotic peptides useful as therapeutic drugs requires strong antibiotic activity against bacterial and fungal cells without hemolytic effect . To this goal, the analogues were designed to increase only net positively charge by Lys-substitution of positions 2, 9, 13, or 16 at the hydrophilic helix face of CRAMP-18 without any change at the hydrophobic helix face . In particular, Lys-substitution (K(2)-CRAMP-18) of position 2 in CRAMP-18 induced the enhanced antibiotic activity without any increase in hemolysis . Thus, this peptide may provide a useful template for the design novel antibiotic peptides for the treatment of infectious diseases . Additional CD spectra studies suggested that the alpha-helical structure of the peptides plays an important role in killing bacterial and fungal cells, but the increase of alpha-helical content is less connected with the enhanced antibiotic activity . J Hosp Infect, 2000 Aug, 45(4), 311 - 7 Assessment of knowledge of guidelines for the prevention of infective endocarditis amongst clinicians in a teaching hospital; Solomon M et al.; A significant minority of instances of endocarditis appear to be the result of invasive procedures performed in susceptible patients with underlying cardiac conditions . Absence, or inappropriate administration, of antimicrobial prophylaxis could expose the patient to the development of a potentially lethal infection . This study was formulated, therefore, to assess the knowledge of guidelines for the prevention of infective endocarditis among hospital-based physicians and surgeons . A multiple choice test was developed, including: (1) cardiac conditions at increased risk for development of infection; (2) procedures more likely to be associated with bacteraemia and endocarditis; and (3) type and route of antimicrobials prescribed when endocarditis prophylaxis is indicated . The quality of the test was determined in several ways . Success was defined as a pass rate of 11 of 18 questions (61%) . The test was taken by 153 of 251 (60%) physicians employed by the hospital; 95 (62%) passed the test . No significant difference in success rates was found according to sex, professional status or medical school . Internists performed substantially better (with a pass rate of 41 of 53, 77%) than both paediatricians (13 of 26, 50%, P<0.05) and surgeons (41 of 74, 55%, P<0.01) . The range of success varied from 100% to 36% according to specialty (P<0.001) . The mean score was 69+/-21 in the study group and 94+/-10 in a control group of 20 infectious disease physicians (P<0.001) . In conclusion, this study demonstrates the need for improved education of hospital-based clinicians regarding endocarditis prophylaxis recommendations. Lett Appl Microbiol, 2000 Aug, 31(2), 163 - 8 Design of self-processing antimicrobial peptides for plant protection; Powell WA et al.; Small antimicrobial peptides are excellent candidates for inclusion in self-processing proteins that could be used to confer pathogen resistance in transgenic plants . Antimicrobial peptides as small as 22 amino acids in length have been designed to incorporate the residual amino acids left from protein processing by the tobacco etch virus'(TEVs') NIa protease . Also, by minimizing the length of these peptides and the number of highly hydrophobic residues, haemolytic activity was reduced without affecting the peptide's antimicrobial activity. Life Sci, 2000 Aug 4, 67(11), 1331 - 44 Growth-altering effects of sodium hypochlorite in cultured human dermal fibroblasts; Hidalgo E et al.; Sodium hypochlorite, the most widely used antimicrobial active chlorine compound in chemical disinfection, is little used as an antiseptic in clinical practice . This study aimed to assess the capacity of hypochlorite to alter human dermal fibroblast growth in vitro in relation to the concentration and exposure time . Effects of decreasing concentrations of hypochlorite (0.5%-0.00025%) on fibroblast adherence capacity and proliferation, according to varying exposure times and fetal calf serum (FCS) concentrations were investigated combining XTT assay, which provides cytochemical quantification of metabolically-active cell number, and total cell protein content, an indirect method for assessing substrate-adhered cell number . Initial cytotoxicity was produced at 0.0075% hypochlorite within contact time of two hours, provoking concentration-dependent cell detachment . From 0.1% upwards, NaOCl exerted a profound cytotoxic effect on fibroblasts . At later stages (4 h) and concentrations > or = 0.01% hypochlorite produced dose-dependent mitochondrial dysfunction: cell survival progressively diminished from 71% to 10% . Cytotoxic effects were not significantly affected by exposure-time periods, probably because maximum chlorine is released within the first four hours . Hypochlorite concentrations from 0.005% to 0.00025% were found to have no inhibitory effects on cell growth; in fact, they appear to exhibit the opposite effect . Increments in protein content found after 24 h exposure ranged from 30% to 120% above control values . Hypochlorite is highly cytotoxic for fibroblasts at concentrations > or = 0.01% provoking concentration-dependent loss of cell adherence capacity and mitochondrial dysfunction . In contrast, a mitogenic effect was observed with concentrations < or = 0.005% which supports NaOCl as a source growth-promoting activity in cultured human fibroblasts . Hypochlorite proved to be a highly reactive molecule which inhibits or stimulates cell division according to the concentration. Helicobacter, 2000 Sep, 5(3), 148 - 54 Helicobacter pylori entry into human gastric epithelial cells: A potential determinant of virulence, persistence, and treatment failures; Bjorkholm B et al.; BACKGROUND AND OBJECTIVES: Intracellular location of Helicobacter pylori in human gastric epithelial cells has been observed in biopsies . Whether this reflects an ability to invade host cells and establish an intracellular niche remains to be determined . METHODS: The interactions between a clinical isolate of H . pylori and primary cell cultures from human gastric epithelium or the human epithelial cell line HEp-2 were monitored using time-lapse photography . This technique allows studies of the dynamics of host-microbial interactions . RESULTS: H . pylori cells readily approached and established close contacts with epithelial cells followed by uptake of the bacteria into the cellular cytoplasm . Entry into epithelial cells was achieved through an active process of bacterial motility and penetration of the cell membranes . In conventional invasion assays using HEp-2 cells, an increased internalization in a strain producing the vacuolating cytotoxin was observed, compared to the isogenic VacA knockout mutant . CONCLUSION: Invasion of gastric epithelium represents a hitherto unappreciated trait of H . pylori that could contribute to the bacterium's ability to establish persistent infection that evades the mucosal immune defense and sometimes also antimicrobial therapy . A small number of bacterial cells with a transient intracellular habitat could serve as a seeder population, providing a backup for a constantly challenged and fluctuating luminal population. Br J Dermatol, 2000 Sep, 143(3), 546 - 50 Skin tolerance and effectiveness of two hand decontamination procedures in everyday hospital use; Winnefeld M et al.; BACKGROUND: Hand decontamination is crucial to control nosocomial infections . The utility of hand decontamination is related not only to its antimicrobial effectiveness, but also to its acceptability by hospital staff . OBJECTIVES: We aimed to assess skin tolerance and antimicrobial effects of two widely accepted hand hygiene measures under in-use conditions . METHODS: Fifty-two nurses were randomly assigned for an 8-day period to either an alcohol-based disinfectant or a hand wash with a non-antiseptic soap . At baseline and at the end of the test period, microbiological hand samples were obtained both before and after a hand hygiene procedure, and skin tolerance was assessed using clinical scores and measurement of transepidermal water loss . RESULTS: Self-assessment of skin condition and grade of skin damage worsened significantly more in the group using soap than in the group using alcoholic disinfectant (P = 0.004 and P = 0.01, respectively) . The alcohol-based rinse was significantly more effective than liquid soap in removing transient contaminant micro-organisms (P = 0.016) . Twenty of 50 hand washes with non-antiseptic soap apparently resulted in bacterial contamination of the hands . At the end of the study, the total bacterial count increased with the increasing number of hand washes in the soap group (P = 0.003), and with the degree of skin damage (P = 0.005) in the antiseptic group . CONCLUSIONS: In everyday hospital practice, alcohol-based disinfectant is more effective and better tolerated than non-antiseptic soap; soap is at risk of spreading contamination; and skin comfort strongly influences the number and the quality of hand hygiene procedures. Proc Natl Acad Sci U S A, 2000 Sep 12, 97(19), 10520 - 5 Toll-related receptors and the control of antimicrobial peptide expression in Drosophila; Tauszig S et al.; Insects defend themselves against infectious microorganisms by synthesizing potent antimicrobial peptides . Drosophila has appeared in recent years as a favorable model to study this innate host defense . A genetic analysis of the regulation of the antifungal peptide drosomycin has demonstrated a key role for the transmembrane receptor Toll, which prompted the search for mammalian homologs . Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria . Here we describe six additional Toll-related genes (Toll-3 to Toll-8) in Drosophila in addition to 18-wheeler . Two of these genes, Toll-3 and Toll-4, are expressed at a low level . Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions . Finally, Toll-5 is expressed only in larvae and adults . By using chimeric constructs, we have tested the capacity of the signaling Toll/IL-1R homology domains of these receptors to activate antimicrobial peptide promoters and found that only Toll and Toll-5 can activate the drosomycin promoter in transfected cells, thus demonstrating specificity at the level of the Toll/IL-1R homology domain . In contrast, none of these constructs activated antibacterial peptide promoters, suggesting that Toll-related receptors are not involved in the regulation of antibacterial peptide expression . This result was independently confirmed by the demonstration that a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide. J Clin Microbiol, 2000 Sep, 38(9), 3194 - 9 Use of real-time PCR and fluorimetry for rapid detection of rifampin and isoniazid resistance-associated mutations in Mycobacterium tuberculosis; Torres MJ et al.; Very fast amplification of DNA in small volumes can be continuously monitored with a rapid cycler that incorporates fluorimetric detection . Primers were designed to amplify a 157-bp fragment of the rpoB gene spanning codons 526 and 531 and a 209-bp fragment of the katG gene spanning codon 315 of Mycobacterium tuberculosis . Most mutations associated with resistance to rifampin (RMP) and isoniazid (INH) in clinical isolates occur in these codons . Two pairs of hybridization probes were synthesized; one in each pair was 3' labeled with fluorescein and hybridized upstream of the codon with the mutation; the other two probes were 5' labeled with LightCycler-Red 640 . Each pair of probes recognized adjacent sequences in the amplicon . After DNA amplification was finished by using a LightCycler, the temperature at which the Red 640 probe melted from the product was determined in a 3-min melt program . Twenty M . tuberculosis clinical isolates susceptible to streptomycin, INH, RMP, and ethambutol and 36 antibiotic-resistant clinical M . tuberculosis isolates (16 resistant to RMP, 16 to INH, and 4 to both antimicrobial agents) were amplified, and the presence of mutations was determined using single-strand conformation polymorphism analysis, the LiQor automated sequencer, and the LightCycler system . Concordant results were obtained in all cases . Within 30 min, the LightCycler method correctly genotyped all the strains without the need of any post-PCR sample manipulation . Overall, this pilot study demonstrated that real-time PCR coupled to fluorescence detection is the fastest available method for the detection of RMP and INH resistance-associated mutations in M . tuberculosis clinical isolates. Phytomedicine, 2000 Jul, 7(4), 335 - 8 In vitro antimycobacterial activities of Physalis angulata L; Pietro RC et al.; The HIV-tuberculosis co-infection has caused an impact on tuberculosis epidemiology all over the world and the efficacies of the therapeutic schemes traditionally prescribed in the treatment of tuberculosis, such as isoniazid, rifampicin and pyrazinamide, have decreased due to the appearance of multidrug-resistant M . tuberculosis strains (MDR) . This work is part of research on natural antimicrobial agents from plant extracts through bioassay-guided fractionation, by in vitro determination of the minimum inhibitory concentration (MIC) using the microdilution method with Alamar blue oxidation-reduction dye . Crude CHCl3 Physalis angulata extracts and physalin-containing fractions displayed antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium malmoense and Mycobacterium intracellulare. Biophys J, 2000 Sep, 79(3), 1465 - 77 Membrane-induced folding of cecropin A; Silvestro L et al.; Lipid membranes manifest a diverse array of surface forces that can fold and orient an approaching protein . To better understand these forces and their ability to influence protein function, we have used infrared spectroscopy with isotopic editing to characterize the 37-residue membrane-active antimicrobial polypeptide cecropin A as it approached, adsorbed onto, and finally penetrated various lipid membranes . Intermediate stages in this process were isolated for study by the use of internal reflection and Langmuir trough techniques . Results indicate that this peptide adopts well-ordered secondary structure while superficially adsorbed to a membrane surface . Its conformation is predominantly alpha-helical, although some beta structure is likely to be present . The longitudinal axis of the helical structure, and the transverse axes of any beta structure, are preferentially oriented parallel to the membrane surface . The peptide expands the membrane against pressure when it penetrates the membrane surface, but its structure and orientation do not change . These observations indicate that interactions between the peptide and deeper hydrophobic regions of the membrane provide energy to perform thermodynamic work, but separate and distinct interactions between the peptide and superficial components of the membrane are responsible for peptide folding . These results have broad implications for our understanding of the mechanism of action and the specificity of these antimicrobial peptides. J Antimicrob Chemother . 2000 Aug;46 Suppl B:III. Preface; Reeves D et al.; Efficient monitoring for the emergence of resistance to various antimicrobial agents has, in the face of global trends in resistance, recently assumed great importance . Many programmes have been developed to survey resistance, each varying in scope or emphasis as well as commitment to long-term monitoring . A programme that specifically addresses pathogens from populations of the most severely ill patients is the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) . This programme was started in 1997 to monitor carbapenem activity in vitro in centres using carbapenems because their prevalent strains were resistant to other beta-lactams and drug classes . Meropenem is a broad-spectrum carbapenem and differs microbiologically from imipenem by having a greater potency in vitro against many Gram-negative pathogens and a slightly lower potency against some Gram-positive pathogens . Meropenem has improved stability to renal-based enzymatic metabolism, and does not require the addition of an enzyme inhibitor such as cilastatin . Material in this publication is based on the many abstracts and oral presentations delivered at recent national and international meetings including: the International Congress of Infectious Disease in Buenos Aires, Argentina (April, 2000); the European Congress of Chemotherapy in Madrid, Spain (May, 2000); and the European Congress of Clinical Microbiology and Infectious Disease in Stockholm, Sweden (May, 2000) . All of the authors are active participants in the MYSTIC programme and bring to it experience in the design of surveillance studies and the detection of resistance mechanisms . Professor Jones discusses the most useful ways of storing and presenting susceptibility data to preserve the long-term value of all results . He argues for the publication of expanded study details and the limited use of MIC(90) values or susceptibility rates . Dr Turner has coordinated the MYSTIC programme, and he summarizes here the similarities and differences in the results seen to date between the Americas, Europe and centres in Asia and the Middle East . The Americas have been one of the most recently monitored regions . Professors Pfaller and Jones give baseline data for the USA (10 sites), Mexico and Brazil . Professor Goossen's article focuses on the results of MYSTIC in the European centres . Doctor Masterton presents a comprehensive overview of various surveillance studies and assesses their value and characteristics for the continued optimal management of infected patients. J Antimicrob Chemother, 2000 Aug, 46 Suppl B, 53 - 58 Surveillance studies: how can they help the management of infection? Masterton RG. The increase in antimicrobial resistance has led to predictions of doom in the international press and to depression in the medical community . It has focused attention upon measures for fighting resistance, foremost of which is susceptibility surveillance . Until recently, global efforts at surveillance have been largely uncoordinated and random . This scene is rapidly changing with the World Health Organization (WHO), among others, leading multidisciplinary, targeted initiatives . In terms of individual surveillance programmes, much has been learned about their design . The best of these, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC), SENTRY and the Alexander Project, involve well-defined patient and organism groups against key denominators, and use standardized, internationally recognized methods that are quality-controlled, explore susceptibility quantitatively and include investigation of resistance mechanisms . Results are rapidly returned to the user . Evidence shows that surveillance, when used to guide policies on antibiotic use and infection control, can be helpful in the fight to control the development and spread of resistance . Further work is required to demonstrate these benefits and quantify them fully. J Antimicrob Chemother, 2000 Aug, 46 Suppl B, 39 - 52 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from Europe: comparison of antibiotic susceptibilities between countries and centre types; Goossens H; The activity of meropenem and five comparators has been studied against 7886 isolates from 29 centres in 10 European countries from 1997 to 1999 as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study . Gram-positive and Gram-negative isolates from intensive care units (ICUs), neutropenia centres, cystic fibrosis (CF) centres and general wards were investigated in Belgium (1 year), Czech Republic (2 years), Germany (3 years), Italy (3 years), Poland (2 years), Russia (2 years), Sweden (2 years), Switzerland (1 year), Turkey (1 year) and UK (3 years) . Resistance to quinolones and aminoglycosides was observed, as was resistance to the cephalosporins and penicillins via extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases . Meropenem showed good activity against the pathogens tested, particularly in CF and neutropenia centres, over the 3 year period . The overall order of potency of the six antimicrobial agents tested was: meropenem > imipenem > piperacillin/tazobactam and ciprofloxacin > ceftazidime > gentamicin . No increase in resistance to the carbapenems, to date, has been detected in any of the European centres included in this study. J Antimicrob Chemother, 2000 Aug, 46 Suppl B, 25 - 37 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from the Americas: resistance implications in the treatment of serious infections; Pfaller MA et al.; The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme aims to provide in vitro surveillance data for geographically diverse institutions where meropenem is available for use . The in vitro activity of meropenem and eight comparator antimicrobial agents against 2340 significant pathogens obtained in 1999 was assessed and compared in 14 study centres in Brazil, Mexico and the USA . Isolates were further characterized for production of extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and carbapenemases . Carbapenems demonstrated their broad spectrum and potency, inhibiting >/=95% of all isolates irrespective of the geographical region or centre type . The overall order of activity of the nine agents tested against all pathogens in 1999 was meropenem (96%) > imipenem (95%) > cefepime (92%) > gentamicin (89%) > piperacillin/tazobactam (88%) > ceftazidime = tobramycin (86%) > cefotaxime (84%) > ciprofloxacin (83%) . Thus far, the results from the Americas indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients . In contrast, other ESBLs, fluoroquinolones and aminoglycosides have lost activity in many institutions as a result of the selection of strains producing ESBLs or having AmpC and other resistance determinants . Carbapenem resistance was observed rarely and at a prevalence similar to those reported in earlier studies . Carbapenems appear to be a continuing reliable option for the treatment of serious nosocomial infection. J Antimicrob Chemother, 2000 Aug, 46 Suppl B, 1 - 8 Detection of emerging resistance patterns within longitudinal surveillance systems: data sensitivity and microbial susceptibility; Jones RN; Communicating information from antimicrobial resistance surveillance study data to microbiologists and physicians can be challenging . Large amounts of data, commonly reaching millions of MICs or zone 20diameter endpoints, must be analysed and condensed to easily-read tables or figures . Furthermore, data must not be prejudged relative to susceptibility categories, because of the diverse nature of interpretive criteria available internationally . An attempt must be made to present results of all surveillance studies in a mode that can be reinterpreted for immediate use in different geographical areas, or used to compare future data with relative ease and high accuracy . Such data displays require peer-reviewed journals to permit greater numbers of more complex tables to present results . The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) study is a year-on-year global surveillance programme in medical centres where meropenem is available for use . We have developed a presentation strategy that expands the long-term clinical value of MYSTIC results . In addition to statistical parameters, tables of cumulative percentages or numbers of strains inhibited at each tested antimicrobial concentration will be presented . Alternative figures (Finland-o-grams) could also be used, but these generally lack precise extractable rates and require more journal space . Regardless of study design, promotion of this presentation philosophy enhances any surveillance study's value to each reader or user and facilitates application to locally appropriate interpretations . The widespread use of these analysis and presentation principles as benchmarks by various resistance studies and networks is strongly encouraged, particularly by investigations across international boundaries. J Antimicrob Chemother, 2000 Aug, 46 Suppl A, 9 - 14 Comparative potency of mecillinam and other beta-lactam antibiotics against Escherichia coli strains producing different beta-lactamases; Sougakoff W et al.; The activity of mecillinam, a beta-lactam antibiotic with high affinity for Gram-negative penicillin-binding protein 2 (PBP2), was assessed against ampicillin-resistant Escherichia coli strains producing beta-lactamases representing the three molecular classes, A (TEM-1 and -3, SHV-3 and IRT-5), C (AmpC) and D (OXA-3) . The antimicrobial activity of mecillinam and other beta-lactam antibiotics was evaluated by determining their MICs on Mueller-Hinton agar . The time course of hydrolysis in crude extracts prepared from the various beta-lactamase-producing strains was also measured and was used to determine the relative rate of hydrolysis and the apparent affinity for ampicillin, cephalothin and mecillinam . When compared with the other beta-lactam antibiotics, mecillinam demonstrated significantly greater antibacterial potency and higher stability to beta-lactamase hydrolysis in TEM-, IRT- and AmpC-producing isolates . These findings confirm that the antimicrobial potency of mecillinam compares favourably with those of the other penicillins included in the present study, suggesting that mecillinam use in the treatment of infections caused by Gram-negative bacteria should be re-evaluated. Infect Control Hosp Epidemiol, 2000 Aug, 21(8), 537 - 45 Antimicrobial use in long-term-care facilities . SHEA Long-Term-Care Committee; Nicolle LE et al.; There is intense antimicrobial use in long-term-care facilities (LTCFs), and studies repeatedly document that much of this use is inappropriate . The current crisis in antimicrobial resistance, which encompasses the LTCF, heightens concerns of antimicrobial use . Attempts to improve antimicrobial use in the LTCF are complicated by characteristics of the patient population, limited availability of diagnostic tests, and the virtual absence of relevant clinical trials . This position paper recommends approaches to management of common infections in LTCF patients and proposes minimal standards for an antimicrobial review program . In developing these recommendations, the position paper acknowledges the unique aspects of provision of care in the LTCF. Eur J Clin Microbiol Infect Dis, 2000 Jul, 19(7), 493 - 500 Clinical impact of an infectious disease service on the management of bloodstream infection; Fluckiger U et al.; The impact of an infectious disease (ID) service on the optimal antibiotic management of 103 patients with bloodstream infections, defined as bacteremia and systemic inflammatory response syndrome, was evaluated . The optimal antibiotic management was defined according to the Sanford Guide to Antimicrobial Therapy (1996) or written internal guidelines . The judgment on optimal antibiotic management was made at the time of reporting the positive blood culture results . Switching from a broad-spectrum to a narrow-spectrum agent was carried out significantly more often by the ID service than by the attending physicians (25 of 25 vs . 20 of 40; P<0.001) . In patients without empirical therapy, the ID service initiated optimal antimicrobial therapy significantly more often than physicians without training in infectious diseases (12 of 12 vs . 4 of 10, P=0.0028) . Three of 12 patients in whom the attending physician misinterpreted the positive blood culture result needed 8 days to 4 months of additional hospitalization . In summary, patients for whom an ID service was provided received appropriate treatment more often and experienced significantly fewer complications. Invest Ophthalmol Vis Sci, 2000 Sep, 41(10), 3026 - 31 Expression of human beta-defensins in intraocular tissues; Haynes RJ et al.; PURPOSE: Defensins are naturally occurring antimicrobial peptides . Recently the authors published evidence of defensin production by the human ocular surface . A study was undertaken to look for intraocular defensins that may account for unexplained antimicrobial activity of intraocular fluids . METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed on human postmortem ciliary body samples for beta defensins-1 (HBD-1) and beta defensin-2 (HBD-2), and alpha defensins 5 and 6 . Induction of defensins by cytokines was analyzed in cultured human ciliary body epithelial (CBE) and retinal pigment epithelial (RPE) cells . Polyclonal antibodies were used to immunoblot aqueous and vitreous to detect HBD-1 and HBD-2 and to estimate their concentration . RESULTS: RT-PCR revealed constitutive HBD-1 message in ciliary body . HBD-2 and alpha defensin 5 and 6 messages were absent . HBD-2 message was induced by cytokine stimulation of both CBE and RPE cells . Immunoblots of vitreous and aqueous stained positively for HBD-1 but not HBD-2 . The estimated aqueous concentration of HBD-1 was less than 16 ng/ml . CONCLUSIONS: This study demonstrates that HBD-1 is constitutively present in the aqueous and vitreous, probably at sub-bacteriocidal concentrations . HBD-2 was absent from aqueous, but cytokine stimulation studies suggest that it may be generated in response to inflammatory cytokines during infections . HBD-2 has a wider antibacterial spectrum, is 10-fold more potent, and may play a more significant role in antimicrobial defense than HBD-1 . The use of defensins therapeutically may be indicated; however, caution is required because defensins also promote cell proliferation and fibrin formation, which are 2 key elements in ocular scarring processes such as proliferative vitreoretinopathy. J Med Chem, 2000 Aug 24, 43(17), 3315 - 21 Anti-Helicobacter pylori agents . 4 . 2-(Substituted guanidino)-4-phenylthiazoles and some structurally rigid derivatives; Katsura Y et al.; In order to find a new class of anti-Helicobacter pylori (H . pylori) agents, a series of 4-{(3-acetamido)phenyl}-2-(substituted guanidino)thiazoles and some structurally rigid analoges were synthesized and evaluated for antimicrobial activity against H . pylori . Among the compounds obtained, high anti-H . pyrori activities were observed in benzyl derivative 34 (MIC = 0.025 microg/mL) and phenethyl derivatives 35 and 36 (MIC = 0.037 microg/mL and 0.017 microg/mL) . Though alkyl derivatives generally showed lower activity, the 2-methoxyethyl derivative 28 preserved significant activity (MIC = 0.32 microg/mL) and also exhibited more potent gastric antisecretory activity than ranitidine . Structural restriction by bridging between the thiazole and the phenyl rings with an alkyl chain did not improve the activity in this series. Crit Care Med, 2000 Aug, 28(8), 2825 - 30 Correlation between endotoxin level and bacterial count in bronchoalveolar lavage fluid of ventilated patients; Nys M et al.; OBJECTIVE: To assess the predictive value of the endotoxin level in the bronchoalveolar lavage (BAL) and to propose to the clinician a guide in the diagnosis of gram-negative bacterial (GNB) pneumonia . DESIGN: Retrospective and prospective studies to investigate the relation between endotoxin level and quantitative bacterial culture of BAL and to test the predictive value of a defined threshold . SETTING: University hospital general intensive care unit . PATIENTS: In the first part of the study, 77 consecutive ventilated patients with clinical suspicion of nosocomial pneumonia between January 1995 and January 1996 . In the second part of the study, 93 consecutive ventilated patients studied prospectively between February 1996 and April 1997 . MEASUREMENTS AND MAIN RESULTS: Quantitative cultures for aerobic bacteria were performed directly from the fluid . Bacterial species were determined with standard techniques . The detection of endotoxin in BAL was made using a quantitative chromogenic Limulus assay . In the retrospective analysis, a significant correlation between quantitative GNB cultures and BAL endotoxin levels was observed (r2 = 0.60, p < .0001) . An endotoxin level > or = 4 endotoxin units/mL (EU/mL) distinguishes patients with a significant GNB count from colonized patients with a sensitivity of 92.6%, a specificity of 81.4% and a correct classification rate of 84.9% . In the prospective analysis, the 4 EU/mL threshold permits identification of infected patients with a sensitivity of 82.2%, a specificity of 95.6%, and a correct classification rate of 90.3% . The receiver operating characteristic curve analysis showed that the Limulus assay still had a good discrimination power in the prediction of significant bacterial count in BAL fluid . CONCLUSIONS: Endotoxin detection immediately after bronchoscopy is a distinct advantage to the clinician because antimicrobial gram-negative therapy may be immediately justified according to the results. J Antibiot (Tokyo), 2000 Jun, 53(6), 597 - 602 Glomosporin, a novel antifungal cyclic depsipeptide from Glomospora sp . I . Production, isolation, physico-chemical properties and biological activities; Sato T et al.; A novel antifungal cyclic depsipeptide termed glomosporin, which has a fatty acyl side chain, was isolated from a barley solid culture of Glomospora sp . The strain was isolated from fallen pine leaves collected in Fukusima Prefecture, Japan and identified as Glomospora sp . BAUA 2825 . Glomosporin was purified by butanol extraction followed by preparative HPLC . Glomosporin showed antimicrobial activity against fungi including clinically important Aspergillus fumigatus. Med Pregl, 2000 Mar-Apr, 53(3-4), 193 - 6 {Drainage of the abdominal cavity and complications in perforating appendicitis in children}; Perovic Z; INTRODUCTION: Controversies regarding drainage and irrigation with antibiotics following perforated appendicitis still exist in literature . Some authors concluded that undrained patients treated with systemic antimicrobial therapy, adequate fluid resuscitation, emergency appendicectomy, peritoneal lavage and primary abdominal wall closure are less exposed to complications . On the other hand, Lund and Murphy and Schwartz and Tapper are still advocating transperitoneal drainage . In that context the aim of this study was to contribute to the current debate with its original results and conclusions . MATERIAL AND METHODS: A series of 56 children, who were operated on for perforated appendicitis during 1996 in Children's Hospital Podgorica and Pediatric Surgery Department of Hospital in Novi Sad, are reviewed . The average age of children in this series was 9.8 years (range, 2-14 years) . All children were divided in two groups: patients included in the first group (n = 36) were treated with aggressive fluid resuscitation, preoperative triple antibiotic therapy, peritoneal lavage, avoidance of transperitoneal drains except those used for well-localized abscesses, primary wound closure and postoperative antibiotic therapy for seven to ten days . In the second group, children were managed in the same way, but silicon tube drainage after appendicectomy was included as well . Patients in both groups were given the same antibiotic therapy: intravenous metronidazole combined with gentamicin and ampicillin . RESULTS: Perforated appendicitis most frequently occurred in the age group between 8 and 15 years (77%), with highest incidence in male children (61%) of all children observed . Positive cultures were obtained from peritoneal swabs from 32 children (57%), of which all had pure growth of aerobes (Escherichia coli and Pseudomonas aerugionosa, mixed or pure) . 36 children were managed by appendectomy followed by peritoneal lavage using a large amount of saline, and intravenous antibiotic therapy (undrained group), while the other 20 children were treated by appendectomy with silicon tube drainage and the same systemic antibiotic therapy (drained group) . A minor complication rate was 43%; this includes 20 cases of wound infection and 4 cases of wound dehiscence . Major complications rate was 5%, which includes 3 cases of ileus . The mortality rate was zero . A comparison of the group that underwent drainage with undrained group showed a relative rate of wound infection to be 19% (undrained) vs . 65% (drained) . According to the x2 test, this can be considered a significant difference, with Yates' correction . Wound dehiscence and ileus were more frequent in the drained group: 10% vs . 6% and 19% vs . 3%, respectively . DISCUSSION: The principal factors contributing to perforation of appendix are: age of children, delays of surgical intervention, family anamnesis, social group and late recognition of symptoms of appendicitis . Fast and adequate surgical intervention followed by adequate antibiotic therapy successfully resolve the cases of perforated appendicitis . The rate of serious post-appendectomy complications of 5-10% established by this study, can be considered as acceptable based on standards presented in the relevant literature . Regarding the reduction of wound infections following perforated appendicitis in children, aggressive therapy consisting of aminoglycosides combined with metronidazole have proven to be very efficient . Complications developed more frequently in the group of drained patients . Our results are in accordance with that achieved by authors cited in introduction: undrained patients are less prone to complications in comparison to drained patients . CONCLUSION: We achieved our lowest rate of serious complications following surgery for pediatric perforated appendix with the use of broad-spectrum antibiotic therapy, primary wound closure and without drainage . Regarding our results, we could propose the same treatment protocol to all in Environ Health Perspect, 2000 Aug, 108(8), 685 - 99 Concentrated swine feeding operations and public health: a review of occupational and community health effects; Cole D et al.; Recent industry changes in swine-management practices have resulted in a growing controversy surrounding the environmental and public health effects of modern swine production . The numerous wastes produced by intensive swine production not only pose a significant challenge to effective environmental management but also are associated with decreased air quality in confinement houses, potentially transferable antimicrobial resistance patterns, and several infectious agents that can be pathogenic to humans . Published studies have documented a variety of contaminants, microbial agents, and health effects in those occupationally exposed to swine, and these have provided the groundwork for an increasing body of research to evaluate possible community health effects . Nonetheless, several factors limit our ability to define and quantify the potential role of intensive swine-rearing facilities in occupational and community health . Our incomplete understanding and ability to detect specific exposures; the complicated nature of disease etiology; pathogenesis; and surveillance; and the inherent difficulties associated with study design all contribute to the inadequate level of knowledge that currently prevails . However; an evaluation of the published literature; and a recognition of the elements that may be compromising these studies; provides the foundation from which future studies may develop. Org Lett, 2000 Sep 7, 2(18), 2837 - 40 Preparation and characterization of cholic acid-derived antimicrobial agents with controlled stabilities; Guan Q et al.; {reaction: see text} Novel cholic acid-derived antimicrobial agents that decompose under mildly basic conditions have been prepared . These compounds range in biological properties from potent antibacterial activity to effective permeabilization of the outer membranes of Gram-negative bacteria. Int J Immunopharmacol, 2000 Oct, 22(10), 775 - 87 Inhibition of lipopolysaccharide-induced I-kappaB degradation and tumor necrosis factor-alpha expression by acriflavine, an antimicrobial agent; Choi SH et al.; Acriflavine neutral (ACF) has been used for treatment of microbial infections for humans and fishes . Effects of ACF on the nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS), an endotoxin, were examined in rat and RAW264.7 cells . Gel retardation analysis revealed that LPS (1 microg/kg) activated NF-kappaB in the liver, whereas pretreatment of rats with ACF (10 mg/kg) completely prevented the NF-kappaB activation . Selectivity of the NF-kappaB DNA binding was confirmed by immunodepletion with anti-p65 and anti-p50 antibodies . Translocation of NF-kappaB to the nucleus is preceded by phosphorylation and proteolytic degradation of inhibitor-kappaBalpha (I-kappaBalpha) subunit . Whereas the level of I-kappaBalpha protein was rapidly decreased after treatment of rats with LPS (1 microg/kg), ACF treatment prior to LPS attenuated the decrease in I-kappaBalpha protein level . LPS-induced increase in the production of TNF-alpha, the principal inflammatory mediator, was prevented by ACF pretreatment by 80% . Stimulation of RAW264.7 cells with 1 microg/ml of LPS caused an increase in DNA binding activity of NF-kappaB, which was 80% inhibited by 1 microg/ml of ACF . LPS reduced I-kappaBalpha level in RAW264.7 cells by 77% . ACF attenuated LPS-induced decrease in I-kappaBalpha protein in a concentration-dependent manner . Production of TNF-alpha by LPS from RAW264.7 cells was decreased by 84% in the presence of ACF . Data showed that ACF inhibited LPS-induced NF-kappaB activation through inhibition of I-kappaBalpha degradation and TNF-alpha production in both rat and RAW264.7 cells . Inhibition of NF-kappaB activation and TNF-alpha production may be associated with the anti-inflammatory activity of ACF. Nature, 2000 Aug 17, 406(6797), 762 - 7 Changing patterns of infectious disease; Cohen ML; Despite a century of often successful prevention and control efforts, infectious diseases remain an important global problem in public health, causing over 13 million deaths each year . Changes in society, technology and the microorganisms themselves are contributing to the emergence of new diseases, the re-emergence of diseases once controlled, and to the development of antimicrobial resistance . Two areas of special concern in the twenty-first century are food-borne disease and antimicrobial resistance . The effective control of infectious diseases in the new millennium will require effective public health infrastructures that will rapidly recognize and respond to them and will prevent emerging problems. Nature, 2000 Aug 17, 406(6797), 735 - 8 Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase; McKinney JD et al.; Mycobacterium tuberculosis claims more human lives each year than any other bacterial pathogen . Infection is maintained in spite of acquired immunity and resists eradication by antimicrobials . Despite an urgent need for new therapies targeting persistent bacteria, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary . Here we report that persistence of M . tuberculosis in mice is facilitated by isocitrate lyase (ICL), an enzyme essential for the metabolism of fatty acids . Disruption of the icl gene attenuated bacterial persistence and virulence in immune-competent mice without affecting bacterial growth during the acute phase of infection . A link between the requirement for ICL and the immune status of the host was established by the restored virulence of delta icl bacteria in interferon-gamma knockout mice . This link was apparent at the level of the infected macrophage: Activation of infected macrophages increased expression of ICL, and the delta icl mutant was markedly attenuated for survival in activated but not resting macrophages . These data suggest that the metabolism of M . tuberculosis in vivo is profoundly influenced by the host response to infection, an observation with important implications for the treatment of chronic tuberculosis. Rev Med Chil, 2000 Mar, 128(3), 267 - 72 {Community acquired pneumonia: from intravenous to oral cephalosporin sequential therapy}; Fernandez P et al.; BACKGROUND: Many hospitalized patients with community acquired pneumoniae can be switched early in the course of therapy from intravenous to oral antibiotics, when there are subjective and objective indicators of improvement . This modality of treatment is called "switch therapy" . AIM: To compare sequential therapy using an oral third generation cephalosporin, with conventional therapy using intravenous ceftriaxone in community acquired pneumonia . PATIENTS AND METHODS: Forty patients admitted due to community acquired pneumonia, initially treated with ceftriaxone 1 g/day i.v . and that showed clinical improvement after three days of therapy, were studied . They were randomly assigned to continue intravenous therapy with ceftriaxone for a total of 10 days or switched to ceftibuten 400 mg od for seven days . RESULTS: Twenty one patients continued i.v . treatment and 19 were switched to ceftibuten . There were no differences between both groups in terms of clinical cure, radiological improvement or normalisation of white blood cell count . CONCLUSIONS: Patients with community acquired pneumonia that have a good initial response to intravenous antimicrobials, can be safely switched to oral therapy . This therapy will shorten hospital stay and thereby treatment costs. Public Health, 2000 Jul, 114(4), 300 - 4 Residues of tetracycline compounds in poultry products in the eastern province of Saudi Arabia; Al-Ghamdi MS et al.; Chicken muscle, liver and egg samples were collected from 33 broiler and 5 layer farms in the eastern province of Saudi Arabia over a period of two years starting from January 1996 . Antibiotic-residue positive samples were identified in the products of 23 (69.7%) broiler and 3 (60%) layer poultry farms . 87% and 100.0% of the antibiotic-residue positive broiler farms were positive for at least one tetracycline compound in raw muscle and liver respectively, while 73.9% and 95.5% were positive for 2 or more tetracyclines in these two tissues, respectively . Furthermore, 82.6% and 95.5% of the antibiotic-residue-positive farms had mean concentrations of at least one tetracycline compound in excess of the permissible maximum residue limit (MRL) in raw muscle and liver, respectively . These compounds also remained chemically detectable after cooking . Tetracycline levels exceeded MRL in 14.4% of antibiotic-positive raw eggs but the overall mean tetracycline concentration in each farm was below MRL . This study confirmed widespread misuse of tetracycline agents including multiple use of drugs belonging to the same pharmacological group and lack of implementation of recommended withdrawal times . This may be contributing to the high resistance rates to tetracyclines in both chicken and human microbial isolates observed in the region . This study, therefore, stresses the need for stricter regulations for the use of antimicrobial drugs in the poultry industry as well as the inspection of chicken for drug residues prior to marketing. Blood, 2000 Sep 1, 96(5), 1979 - 84 Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection; Mastroianni CM et al.; Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human immunodeficiency virus (HIV)-infected patients . Interleukin (IL)-15 is a recently discovered cytokine that potentiates antimicrobial functions of normal PMNs . We evaluated the in vitro effect of IL-15 on chemotaxis and fungicidal activity of PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral suppression after 52 to 130 weeks of highly active antiretroviral therapy (HAART), and 12 patients with treatment failure . We also studied oxidative burst and apoptosis of PMNs in 5 patients with untreated advanced HIV infection . Twelve healthy donors were included as controls . Chemotaxis and fungicidal activity of unprimed PMNs was significantly lower in patients with untreated HIV infection compared with controls . After incubation with IL-15, a significant increase in PMN chemotaxis and fungicidal activity was found; moreover, IL-15 induced a significant reduction in the number of apoptotic HIV(+) PMNs . IL-15 did not modulate oxidative burst of HIV(+) PMNs as measured by chemiluminescence production . The in vitro priming of PMNs with IL-15 determined a complete reversal of defective chemotaxis and killing in all HAART-treated patients with long-term HIV suppression . IL-15 significantly enhanced chemotaxis and fungicidal activity also in patients with HAART failure . In conclusion, IL-15 is an important cytokine in the activation of the functional properties of HIV(+) PMNs, by delaying apoptosis and enhancing chemotaxis and fungicidal activity . The potent stimulant effect of IL-15 on PMN function was observed in antiretroviral naive patients as well as in individuals who were receiving HAART, including those with treatment failure . (Blood . 2000;96:1979-1984) Infection, 2000 Jul-Aug, 28(4), 246 - 50 Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis; Eucker J et al.; An 18-year-old woman was admitted to hospital because of subcutaneous hematoma and fever of unknown origin . Acute myeloid leukemia was diagnosed and empirical antimicrobial treatment and induction chemotherapy were started . After initial defervescence, fever relapsed 2 days after the onset of neutropenia . The CT scan of the lung was consistent with an invasive fungal infection . Treatment with amphotericin B was started and antimicrobial treatment was continued with liposomal amphotericin B because of an increase in creatinine later . The fever persisted and the patient suddenly developed progressive neurological symptoms . CT scan of the head suggested cerebral infarction and angiography of the extra- and intracranial arteries showed signs of vasculitis . Six days after the onset of neurological symptoms cerebral death was diagnosed . Autopsy revealed non-septate, irregularly branched hyphae in various histologic sections including brain . Absidia corymbifera could be isolated from lung tissue confirming the diagnosis of disseminated mucormycosis . In this case, angiographic findings suggested severe cerebral vasculitis which was in fact caused by thromboembolic dissemination of fungal hyphae . This case underlines the fact that cerebral symptoms in febrile neutropenic patients are highly indicative for fungal infections of the brain. J Bacteriol, 2000 Sep, 182(18), 5091 - 6 Metronidazole activation is mutagenic and causes DNA fragmentation in Helicobacter pylori and in Escherichia coli containing a cloned H . pylori RdxA(+) (Nitroreductase) gene; Sisson G et al.; Much of the normal high sensitivity of wild-type Helicobacter pylori to metronidazole (Mtz) depends on rdxA (HP0954), a gene encoding a novel nitroreductase that catalyzes the conversion of Mtz from a harmless prodrug to a bactericidal agent . Here we report that levels of Mtz that partially inhibit growth stimulate forward mutation to rifampin resistance in rdxA(+) (Mtz(s)) and also in rdxA (Mtz(r)) H . pylori strains, and that expression of rdxA in Escherichia coli results in equivalent Mtz-induced mutation . A reversion test using defined lac tester strains of E . coli carrying rdxA(+) indicated that CG-to-GC transversions and AT-to-GC transitions are induced more frequently than other base substitutions . Alkaline gel electrophoretic tests showed that Mtz concentrations near or higher than the MIC for growth also caused DNA breakage in H . pylori and in E . coli carrying rdxA(+), suggesting that this damage may account for most of the bactericidal action of Mtz . Coculture of Mtz(s) H . pylori with E . coli (highly resistant to Mtz) in the presence of Mtz did not stimulate forward mutation in E . coli, indicating that the mutagenic and bactericidal products of Mtz metabolism do not diffuse significantly to neighboring (bystander) cells . Our results suggest that the widespread use of Mtz against other pathogens in people chronically infected with H . pylori may stimulate mutation and recombination in H . pylori, thereby speeding host-specific adaptation, the evolution of virulence, and the emergence of resistance against Mtz and other clinically useful antimicrobials. Scand J Infect Dis, 2000, 32(4), 403 - 6 Comparison of the effects of hospitalization and antibiotic usage on the aerobic intestinal flora; Palabiyikoglu I et al.; Antimicrobial resistance among bacteria has arisen ever since antimicrobial agents were introduced in the clinic . Unfortunately, it seems that resistance is now emerging at a more rapid rate than ever before, as a consequence of the widespread use of antimicrobial agents . The spread of these multiresistant microorganisms is an increasing threat in many countries . The human intestinal flora is a huge potential reservoir of resistant microorganisms . Antimicrobial resistance in clinical isolates may cause serious infections and treatment failure, and lead to the use of higher doses or more toxic alternative drugs . This study was planned so as to compare the effects of hospitalization and antibiotic usage on the aerobic intestinal flora and included 43 hospitalized adult patients without any previous history of hospitalization and antibiotic usage during the last 30 d . Patients were divided according to their antimicrobial therapy, into treated and untreated groups . The individual use of antimicrobials was recorded . Antibiotic usage was found to be more effective on the aerobic intestinal flora compared with hospitalization without such medication. J Endourol, 2000 Jun, 14(5), 395 - 400 Infection-resistant nonleachable materials for urologic devices; Williams JF et al.; Bacterial colonization is the primary clinical problem faced by the surgeon and medical device innovator . Despite the absence of effective systemic treatment, medical implants and devices have been deployed with increasing success over the past five decades . Infection-resistant materials (IRMs) are a relatively recent addition to the science of implant and device development . The first IRM utilized leachable antimicrobial agents . Nonleachable technologies are being developed, some of which have the potential to make organ replacement even more successful in the future. Vet Res, 2000 Jul-Aug, 31(4), 373 - 95 Guidelines and recommendations for antimicrobial minimum inhibitory concentration (MIC) testing against veterinary mycoplasma species . International Research Programme on Comparative Mycoplasmology; Hannan PC; The absence of standardised procedures for minimum inhibitory concentration (MIC) testing of antimicrobial agents against veterinary mycoplasma and ureaplasma species (Mollicutes) has made it difficult to compare results originating from different laboratories . This report, prepared on behalf of the International Research Programme on Comparative Mycoplasmology (IRPCM), offers guidelines and recommendations for veterinary MIC testing of these organisms in an effort to rectify this problem . The subjects discussed include suitable media for broth and agar MIC assays, storage and preparation of antimicrobial agents, standardisation of mycoplasma inocula for MIC tests, validation of equipment, incubation conditions, and determination of MIC end points . A standard medium for all veterinary mycoplasma MIC tests cannot currently be recommended, owing to the diversity of nutritional requirements of different mycoplasma species . Instead mycoplasma broths or agars giving optimal growth of specific mycoplasmas or ureaplasmas are recommended, as suboptimal growth may lead to falsely low MIC results . The importance of using standardised mycoplasma inocula, for assays using either solid or liquid media is stressed . The growth phase may be less important as lag phase and logarithmic phase cultures of Mycoplasma gallisepticum, M . synoviae, M . bovis and M . hyopneumoniae have given very similar results in liquid MIC assays . The liquid method of Tanner and Wu and the agar method described by Hannan et al . are compared and described in detail . Methods for calculating MIC50s and MIC90s are described and the interpretation of results discussed . Methods for assessing mycoplasmacidal (MMC) activity of antimicrobial agents are also described . Adoption of these guidelines should lead to more consistent MIC results being obtained between laboratories. Altern Med Rev, 2000 Aug, 5(4), 372 - 5 Green tea; Prophylactic antibiotics in aesthetic and reconstructive surgery; Department of Plastic and Reconstructive Surgery, Rambam Medical Center, Technion Institute of Technology, Haifa, IsraelThe widespread use of antibacterial agents for prophylaxis has altered surgical practice markedly in the past 20 years and now represents one of the most frequent uses of antibiotics in hospitals, accounting for as many as half of all antibiotics prescribed . The present study was undertaken to determine the patterns of and reasons for antibacterial agent usage by today's practicing plastic surgeons in Israel . A survey of 78 Israeli plastic surgeons certified by the Israeli Association of Plastic Surgery was conducted . Questionnaires were mailed to all the certified plastic surgeons; 66 (84.6%) were completed and returned . The results indicate that prophylactic antibiotics are administered in a high percentage of aesthetic and reconstructive surgeries except for those in eyelids and nose . Most of the surgeons prefer to prescribe cephalosporins as their antibiotics of choice and the timing of administration is before or at the beginning of surgery . Placement of drains did not change the decision to use prophylaxis . Diabetes mellitus, steroid treatment, and chronic lung disease have a direct influence on the decision to use antibiotics; however, conditions such as ischemic heart disease, hypertension, and cigarette smoking do not influence their use . Personal experience was the main reason for prescribing antimicrobial agents . We conclude that although the infection rate in aesthetic and reconstructive operations is extremely low, most Israeli plastic surgeons still prefer to administer prophylactic antibiotics though no scientific hard data is available. J Am Vet Med Assoc, 2000 Aug 15, 217(4), 541 - 5 Association between measures of milk quality and risk of violative antimicrobial residues in grade-A raw milk; Saville WJ et al.; OBJECTIVE: To determine whether bulk-tank standard plate counts or plate loop counts and bulk-tank somatic cell counts (SCC) were associated with detection of violative antimicrobial residues in milk from dairy cattle . DESIGN: Longitudinal study . PROCEDURE: Information for 1994 through 1997 was obtained from a large milk marketing cooperative that operated in multiple states throughout the northeastern and midwestern United States (16,831 herd-years of information from 6,546 farms) and from the Ohio Department of Agriculture Grade-A Milk Certification Program (12,042 herd-years of information from 4,022 farms) . Data were analyzed by use of multivariate logistic regression . RESULTS: For both data sets, odds that a violative antibiotic residue would be detected increased as mean SCC for the herd-year increased . Standard plate counts and plate loop counts were not associated with odds that a violative antibiotic residue would be detected . CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that the odds that a violative antibiotic residue would be found in bulk-tank milk increased as mean SCC for the herd-year increased . This suggests that management practices that would be expected to influence SCC may also influence the risk of antibiotic residue violations. Rev Clin Esp, 2000 Jun, 200(6), 315 - 7 {Bacteremia caused by Stenotrophomonas maltophilia: epidemiology, clinical features, and prognosis factors}; Herrero Romero M et al.; The epidemiologic, clinical and prognostic characteristics of Stenotrophomonas maltophilia bacteremias for a six-year period (January 1993 to December 1998) were reviewed . Twenty episodes of S . maltophilia bacteremia were include, which represented 0.62% of all bacteremias caused by gram-negative rods during that period . Seventy percent of bacteremias were clinically significant . The most common predisposing factors were the previous use of antimicrobial agents and the presence of vascular catheters . In most cases (57%), the origin of bacteremia was the intravascular catheter . The course of patients was favorable and all patients cured. Ceska Slov Farm, 2000 Mar, 49(2), 68 - 74 {Chemical structure of quinolones and their antibacterial activity . II . 4-quinolones: their occurrence in nature and biological properties}; Milata V; The review paper deals with the natural occurrence, biological properties, and uses of 4-quinolones concentrating on 3-substituted-4-quinolones and their antimicrobial activity. Baillieres Best Pract Res Clin Rheumatol, 1999 Mar, 13(1), 149 - 61 Diagnosis and treatment of diabetic foot infections; Tan JS et al.; Prompt clinical diagnosis and timely treatment are the hallmarks of the proper care of diabetic patients with foot infections . The importance of careful clinical foot examination cannot be overemphasized . When infection is suspected, effort should be made to search for deeper infections, especially osteomyelitis . Numerous imaging techniques are available, but their cost-effectiveness has not been fully determined . Radiography of the foot is less sensitive but can provide useful information at a lower cost . Radio-isotope studies have not yielded consistent results, but the newer techniques deserve attention . Microbiological diagnosis should be attempted using only deep tissue culture, including bone biopsy . The primary aim of treatment of the infected foot is to restore ambulation . Timely surgical intervention and appropriate antimicrobial therapy can reduce the incidence of above-ankle amputation and reduce the length of hospital stay . Baillieres Best Pract Res Clin Rheumatol, 1999 Mar, 13(1), 129 - 47 Acute and chronic adult osteomyelitis and prosthesis-related infections; Munoz P et al.; Both acute and chronic osteomyelitis are causes of rising concern, mainly because of the increasing number of traumatic accidents, the appearance of new groups of patients at risk, the widespread use of prosthetic devices and the emergence of new patterns of antimicrobial resistance . Classification systems, clinical features and risk factors will be reviewed . Diagnosis is usually clinical and microbiological, but imaging techniques such as plain radiography, radionuclide imaging, computed tomography and magnetic resonance imaging are commonly used . Decisions regarding the best imaging modality can be challenging and should reflect the location of the suspected infection and any associated illnesses or bone disorders . Osteomyelitis is characteristically recurrent, needs multiple surgical interventions and is resistant to short courses of therapy . The application of more precise diagnostic techniques and the availability of non-toxic, highly efficacious oral antimicrobial agents frequently permit a long-term ambulatory approach . The optimal length of therapy has not been established . Antimicrob Agents Chemother, 2000 Sep, 44(9), 2561 - 3 Activities of antimicrobial agents against intracellular pneumococci; Mandell GL et al.; Pneumococci can enter and survive inside human lung alveolar carcinoma cells . We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells . We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms. Antimicrob Agents Chemother, 2000 Sep, 44(9), 2557 - 60 In vitro activity of trovafloxacin compared to those of five antimicrobials against mycoplasmas including Mycoplasma hominis and Ureaplasma urealyticum fluoroquinolone-resistant isolates that have been genetically characterized; Bebear CM et al.; The in vitro activity of trovafloxacin against 125 strains of Mycoplasma species and Ureaplasma urealyticum, including fluoroquinolone-susceptible and fluoroquinolone-resistant species, was compared to those of other fluoroquinolones, doxycycline, and erythromycin . The MIC at which 90% of isolates are inhibited for all fluoroquinolone-susceptible strains was 0.25 microg/ml . Whatever the associated mutations, trovafloxacin exhibited greater activity than the other fluoroquinolones tested against fluoroquinolone-resistant Mycoplasma hominis and U . urealyticum isolates. Antimicrob Agents Chemother, 2000 Sep, 44(9), 2507 - 13 Bactericidal activity of micromolar N-chlorotaurine: evidence for its antimicrobial function in the human defense system; Nagl M et al.; N-Chlorotaurine, the main representative of long-lived oxidants found in the supernatant of stimulated granulocytes, has been investigated systematically with regard to its antibacterial activity at different physiological concentrations for the first time . N-Chlorotaurine (12.5 to 50 microM) demonstrated a bactericidal effect i.e., a 2 to 4 log(10) reduction in viable counts, after incubation at 37 degrees C for 6 to 9 h at pH 7.0, which effect was significantly enhanced in an acidic milieu (at pH 5 . 0), with a 3 to 4 log(10) reduction after 2 to 3 h . Moreover, bacteria were attenuated after being incubated in N-chlorotaurine for a sublethal time, as demonstrated with the mouse peritonitis model . The supernatant of stimulated granulocytes exhibited similar activity . Transmission electron microscopy revealed changes in the bacterial cell membrane and cytoplasmic disintegration with both reacting systems, even in the case of a mere attenuation . The results of this study suggest a significant bactericidal function of N-chlorotaurine and other chloramines during inflammation. Antimicrob Agents Chemother, 2000 Sep, 44(9), 2442 - 51 Antimalarial activities of dermaseptin S4 derivatives; Krugliak M et al.; The hemolytic antimicrobial peptide dermaseptin S4 was recently shown to exert antimalarial activity . In this study, we attempted to understand the underlying mechanism(s) and identify derivatives with improved antimalarial activity . A number of dermaseptin S4 derivatives inhibited parasite growth with a 50% inhibitory concentration (IC(50)) in the micromolar range . Among these, the substituted S4 analog K(4)K(20)-S4 was the most potent (IC(50) = 0.2 microM), while its shorter version, K(4)-S4(1-13)a, retained a considerable potency (IC(50) = 6 microM) . Both K(4)K(20)-S4 and K(4)-S4(1-13)a inhibited growth of the parasites more at the trophozoite stage than at the ring stage . Significant growth inhibition was observed after as little as 1 min of exposure to peptides and proceeded with nearly linear kinetics . The peptides selectively lysed infected red blood cells (RBC) while having a weaker effect on noninfected RBC . Thus, K(4)K(20)-S4 lysed trophozoites at concentrations similar to those that inhibited their proliferation, but trophozoites were >30-fold more susceptible than normal RBC to the lytic effect of K(4)K(20)-S4, the most hemolytic dermaseptin . The same trend was observed with K(4)-S4(1-13)a . The D isomers of K(4)K(20)-S4 or K(4)-S4(1-13)a were as active as the L counterparts, indicating that antimalarial activity of these peptides, like their membrane-lytic activity, is not mediated by specific interactions with a chiral center . Moreover, dissipation of transmembrane potential experiments with infected cells indicated that the peptides induce damage in the parasite's plasma membrane . Fluorescence confocal microscopy analysis of treated infected cells also indicated that the peptide is able to find its way through the complex series of membranes and interact directly with the intracellular parasite . Overall, the data showed that dermaseptins exert antimalarial activity by lysis of infected cells . Dermaseptin derivatives are also able to disrupt the parasite plasma membrane without harming that of the host RBC. CMAJ, 2000 Aug 8, 163(3), 301 - 9 The role of DNA amplification technology in the diagnosis of infectious diseases; Louie M et al.; Nucleic acid amplification and detection methods developed in the past decade are useful for the diagnosis and management of a variety of infectious diseases . The most widely used of these methods is the polymerase chain reaction (PCR) . PCR assays can detect rapidly and accurately the presence of fastidious and slow-growing microorganisms, such as Chlamydia, mycoplasmas, mycobacteria, herpesviruses and enteroviruses, directly from clinical specimens . Commercial PCR assays for the diagnosis of tuberculosis and genital C . trachomatis infection are now routinely used in many diagnostic laboratories . Assays have also been developed that can detect antimicrobial resistance and are used to identify the cause of infection by organisms that cannot be cultivated . The value of viral load measurement by nucleic acid amplification in the management of patients with HIV infection or hepatitis C has also been well established . However, evaluations of this technology for rapid microbial diagnosis have generally been limited by small samples, and the cost of these assays may be as high as Can$125 per test . As nucleic acid amplification methods continue to evolve, their role in the diagnosis and management of patients with infectious diseases and their impact on clinical outcomes will become better defined. Microbiol Res, 2000 Jul, 155(2), 69 - 77 Effect of lysozyme or modified lysozyme fragments on DNA and RNA synthesis and membrane permeability of Escherichia coli; Pellegrini A et al.; Previously we have shown that chicken egg white lysozyme, an efficient bactericidal agent, affects both gram-positive and gram-negative bacteria independently of its muramidase activity . More recently we reported that the digestion of lysozyme by clostripain yielded a pentadecapeptide, IVSDGNGMNAWVAWR (amino acid 98-112 of chicken egg white lysozyme), with moderate bactericidal activity but without muramidase activity . On the basis of this amino acid sequence three polypeptides, in which asparagine 106 was replaced by arginine (IVSDGNGMRAWVAWR, RAWVAWR, RWVAWR), were synthesized which showed to be strongly bactericidal . To elucidate the mechanisms of action of lysozyme and of the modified antimicrobial polypeptides Escherichia coli strain ML-35p was used . It is an ideal organism to study the outer and the inner membrane permeabilization since it is cryptic for periplasmic beta-lactamase and cytoplasmic beta-galactosidase unless the outer or inner membrane becomes damaged . For the first time we present evidence that lysozyme inhibits DNA and RNA synthesis and in contrast to the present view is able to damage the outer membrane of Escherichia coli . Blockage of macromolecular synthesis, outer membrane damage and inner membrane permeabilization bring about bacterial death . Ultrastructural studies indicate that lysozyme does not affect bacterial morphology but impairs stability of the organism . The bactericidal polypeptides derived from lysozyme block at first the synthesis of DNA and RNA which is followed by an increase of the outer membrane permeabilization causing the bacterial death . Inner membrane permeabilization, caused by RAWVAWR and RWVAWR, follows after the blockage of macromolecular synthesis and outer membrane damage, indicating that inner membrane permeabilization is not the deadly event . Escherichia coli bacteria killed by the substituted bactericidal polypeptides appeared, by electron microscopy, with a condensed cytoplasm and undulated bacterial membrane . So the action of lysozyme and its derived peptides is not identical. Monaldi Arch Chest Dis, 2000 Apr, 55(2), 101 - 5 Prevalence, age distribution and aetiology of bronchiectasis: a retrospective study on 144 symptomatic patients; Scala R et al.; The incidence of bronchiectasis (BCT) has probably decreased in developed countries in recent years, but reliable statistical data on its occurrence are still lacking . The aim of the present study was to retrospectively evaluate the prevalence, age distribution and aetiology of BCT, diagnosed in a selected series of symptomatic patients of a Western country by using bronchography . The authors analysed the main known predisposing and associated conditions (PACs), and the occurrence and age distribution of BCT in 144 consecutive patients who underwent bronchological examination (fibreoptic bronchoscopy and bronchography) in the years 1987-1994 because of recurrent purulent bronchitis and/or haemoptysis . The overall prevalence of BCT was 34% (49/144); its age distribution was: 17.2% (0-10 yrs), 43.7% (11-20 yrs), 38% (21-30 yrs), 37.5% (31-40 yrs), 33.3% (41-50 yrs), 40% (51-60 yrs), and 20% (61-70 yrs) . Thirty-one PACs were found in 29/144 patients of the whole study group . The prevalence of BCT was significantly higher in the subgroup of 29 patients with PACs than in the subgroup of 115 patients without PACs (75.9% versus 23.5%; p < 0000001) . The aetiology of BCT was mainly unexplained, as it was only possible to detect 24 PACs in 22/49 patients with BCT (44.9%): congenital, genetic and immune disorders (eight), localized airways obstructive diseases (five), pulmonary infections (three), bronchial asthma (two), pulmonary lobar fibrosis (two), ulcerative colitis (two), dermatomiositis (one), and toxin inhalation (one) . The authors conclude that bronchiectasis still occurs in a large percentage of symptomatic patients of a developed country in the post-antimicrobial era, especially in the second to sixth decades, as well as in the presence of predisposing and associated conditions; its aetiology remains unknown in more than half of cases. J Foot Ankle Surg, 2000 Jul-Aug, 39(4), 253 - 7 Antibiotic selection for diabetic foot infections: a review; Cunha BA; Foot infections account for about 20% of all hospitalizations in people with diabetes and at least 50% of all nontraumatic lower-limb amputations performed annually in the United States . As many as 25% of all diabetics are expected to develop severe foot problems at some point in their lifetimes . Diabetic foot infections are generally more severe and more difficult to treat than infections in nondiabetics . This is due to impaired microvascular circulation, neuropathy, anatomical alterations, and impaired immune capacity in diabetic patients . Most moderate-to-severe soft-tissue diabetic foot infections are polymicrobial (i.e., due to gram-positive, gram-negative, aerobic, and anaerobic pathogens) . Empiric antibiotic therapy should include broad-spectrum antibiotics capable of covering the most common pathogens found in diabetic infections . Other factors to consider in antibiotic selection include the severity of the infection, the presence of peripheral vascular disease, and the possibility of drug-resistant organisms in the infection . This review summarizes the clinical presentation and antimicrobial therapy of diabetic foot infections. Chirurg, 2000 Jun, 71(6), 702 - 6 {Do guidelines bring an improvement in the perioperative course? A study of perioperative antibiotic prophylaxis}; Wolters U et al.; INTRODUCTION: Although the effectiveness of perioperative antibiotic prophylaxis is proven, it is not used adequately . The aim of this study was to evaluate whether hospital-based guidelines are useful tools to improve the management of perioperative antimicrobial prophylaxis . MATERIAL: In a retrospective study the actual quality of perioperative antibiotic prophylaxis as given by the criteria choice of drugs, dosage, timing, continuation and 2nd dose after > 3 h was evaluated . After information and establishment of adequate guidelines we started a prospective analysis to test compliance and rate of adequate prophylaxis . Differences were calculated according to the chi 2-test with P < 0.05 significance niveau . RESULTS: The percentage of cases in which antibiotics were indicated but not administered was reduced from 15.5% to 8.4% . Compared to the result of the retrospective analysis, the prospective study showed a significantly higher percentage of adequately administered antibiotics (35.7% vs . 63.5%) . This was mainly due to the compliance with dosage recommendations and to the 2nd dose in longer surgical procedures . DISCUSSION: Guidelines lead to a significant improvement in perioperative antibiotic prophylaxis . To increase this effect, further approaches such as integration of guidelines into computer-based systems should be evaluated. Monaldi Arch Chest Dis, 2000 Jun, 55(3), 231 - 6 Potential role of macrolides in the treatment of asthma; Cazzola M et al.; A body of evidence highlights the fact that macrolides may not only enhance the host defence system through increased cytokine synthesis by host cells but also exhibit anti-inflammatory activity by including anti-inflammatory cytokines . Several authors have stressed the possibility that macrolides are useful in the treatment of asthma because of their antimicrobial activity rather than any anti-inflammatory action . However, the mechanism of action of macrolides in improving asthma and reducing airway responsiveness is speculated not to be due to their antibiotic properties, especially when these agents are active in noninfectious asthma . The steroid-sparing effect of macrolide antibiotics has been postulated to contribute to their beneficial actions in the treatment of asthma . Nevertheless, a number of studies have shown that macrolides antibiotics have an anti-inflammatory effect which is independent of their antibiotic action or any influence on corticosteroid metabolism . Macrolides may be useful in the treatment of patients with steroid-dependent asthma, probably because they inhibit eosinophilic inflammation . It has also been suggested that the effect of macrolides on bronchial hyperresponsiveness is mediated by their inhibitory action on superoxide production and chemotaxis of polymorphonuclear neutrophils and the mixed lymphocyte reaction . In any case, it is clear that the mechanism of action of macrolides in asthmatic syndrome is not unequivocal . Only well-designed and -conducted clinical studies are capable of assessing the efficacy and safety of immunosuppressive macrolides in the treatment of asthma. Immunol Cell Biol, 2000 Aug, 78(4), 311 - 7 Life on the inside: probing mycobacterium tuberculosis gene expression during infection; Triccas JA et al.; The identification of Mycobacterium tuberculosis genes specifically expressed during infection is a key step in understanding mycobacterial pathogenesis . Such genes most likely encode products required for survival within the host and for progressive infection . Recent advances in mycobacterial genetics have permitted the development of new techniques and the adaptation of existing methods to analyse mycobacterial in vivo gene expression and virulence . This has revealed a subset of M . tuberculosis genes that are differentially expressed during infection and has demonstrated that a number of components contribute to the virulence of the organism . This information is expected to provide new strategies to prevent tuberculosis infection, new targets for antimicrobial therapy and new insights into the infectious process. CLAO J, 2000 Jul, 26(3), 134 - 40 Evaluation of the PuriLens contact lens care system: an automatic care system incorporating UV disinfection and hydrodynamic shear cleaning; Choate W et al.; PURPOSE: This study evaluates lens care using the PuriLens System, an advanced way to clean and disinfect soft hydrophilic lenses using subsonic agitation and UV radiation, respectively . METHODS: A two-period crossover lens cleaning and safety investigation was conducted using 80 patients . Disinfecting efficacy was tested in accordance with standard FDA protocols . Lens compatibility was studied with Group I and Group IV lenses during the equivalent of a 6-month care regimen by measuring: lens power, base curve, wet diameter, refractive index, clarity, and tint . Safety was evaluated through slit-lamp findings, wearing time, comfort, and visual acuity . RESULTS: The mean wearing time of patients in the study was 13.79 hours . No slit lamp findings greater than grade 2 were noted . Visual acuity was 20/25 or better in 92.5% of examinations . None of the patients lost more than two lines of acuity . Lens surface evaluation showed no deposits (grade 0) to very slight deposits (grade 1) in 94.4% of examinations . Lenses cleaned with the PuriLens System were cleaner by a statistically significant margin (P=0.02) compared to lenses digitally cleaned with a leading multi-purpose solution (ReNu, Bausch & Lomb) . Overall, neither the Group I nor Group IV lenses were affected after 180 cleaning cycles . CONCLUSIONS: The PuriLens System provides automatic lens care compliance, superior antimicrobial efficacy, and eliminates the need for daily digital cleaning. CLAO J, 2000 Jul, 26(3), 120 - 6 Broad spectrum antimicrobial activity of a new multi-purpose disinfecting solution; Rosenthal RA et al.; PURPOSE: There has been increasing awareness of the need for more powerful contact lens disinfectants, ideally having low toxicity and allergenicity to ocular tissue . Opti-Free Express with ALDOX Multi-Purpose Disinfecting Solution (MPDS) was recently marketed as a new multi-purpose disinfecting solution for soft contact lenses . MPDS contains two antimicrobial agents, polyquaternium-1 and myristamidopropyl dimethylamine, to broaden the range of antimicrobial activity . The purpose of this study was to evaluate the antimicrobial activity of MPDS against microorganisms that have been reported as contact lens and lens case contaminants and causative agents of microbial keratitis . METHODS: MPDS was challenged with high numbers of gram-positive and gram-negative bacteria, yeast, mold, and Acanthamoeba . Several lots of product were challenged with at least three separate inocula of each isolate . After exposure to the disinfecting solution, a sample was removed from the product and plated for survivors by suitable recovery methods . The plates were incubated and the number of survivors was enumerated . RESULTS: The results showed that MPDS was bactericidal, fungicidal and amoebicidal against an extensive variety of environmental contaminants of lens care accessories and ocular pathogens . MPDS was capable of killing a broad spectrum of microorganisms . The log reduction exceeded the primary criteria for disinfecting products and produced a notable reduction of other clinical and environmental isolates as well . CONCLUSIONS: Opti-Free Express MPDS contains antimicrobial agents that can kill an extensive spectrum of many different types of microorganisms that may contaminate contact lenses and solutions. J Neurol Neurosurg Psychiatry, 2000 Sep, 69(3), 381 - 4 Infection related to intracranial pressure monitors in adults: analysis of risk factors and antibiotic prophylaxis; Rebuck JA et al.; OBJECTIVE: Infection is a complication related to intracranial pressure monitoring devices . The timing, duration, and role of prophylactic antimicrobial agents against intracranial pressure monitor (ICPM) related infection have not previously been well defined . Risk factors and selection, duration, and timing of antibiotic prophylaxis in patients with ICPMs were evaluated . METHODS: Records of all consecutive patients who underwent ICPM insertion between 1993 and 1996 were reviewed . Patients included were older than 12 years with an ICPM placed for at least 24 hours . Exclusion criteria consisted of ICPM placed before admission or documented CSF infection before or at the time of insertion . Standard criteria were applied to all patients for diagnosis of CSF infection . RESULTS: A total of 215 patients were included, 16 (7.4%) of whom developed CSF infection . Antibiotic prophylaxis for ICPM placement was administered to 63% of infected and 59% of non-infected patients . Vancomycin (60%) and cefazolin (34%) were used most often . Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of those without CSF infection received their first antibiotic dose within the 2 hours before ICPM insertion . Risk factors for CSF infection included duration of monitoring greater than 5 days (RR 4.0 (1.3-11.9)); presence of ventriculostomy (RR 3.4 (1.0-10.7)); CSF leak (RR 6.3 (1.5-27.4)); concurrent systemic infection (RR 3.4 (1.2-9.5)); or serial ICPM (RR 4.9 (1 . 7-13.8)) . CONCLUSIONS: Administration of antibiotics to patients before or at the time of ICPM placement did not decrease the incidence of CSF infection . Patients found to be at greater risk for infection at our institution included duration of ICPM greater than 5 days, use of ventricular catheter, CSF leak, concurrent systemic infection, or serial ICPM. J Food Prot, 2000 Aug, 63(8), 1087 - 92 Acidified sodium chlorite antimicrobial treatment of broiler carcasses; Kemp GK et al.; An acidified sodium chlorite (ASC) solution was investigated for its antimicrobial effects on broiler carcasses processed under conditions similar to those used in U.S . commercial poultry facilities . Of particular interest was the ability of the ASC solution to reduce natural bioburden in a prechill procedure . A number of parameters such as pretreatment washing of carcasses with water (no wash versus water wash), ASC concentration (500, 850, and 1,200 ppm), method of application (spray versus dip), and method of acid activation (phosphoric acid versus citric acid) were explored to evaluate disinfection conditions . ASC dip solutions (18.9 liters) were freshly prepared for groups of five prechill eviscerated carcasses per treatment (n = 10 carcasses) . ASC treatment was shown to be an effective method for significantly reducing naturally occurring microbial contamination on carcasses . Reductions following immersion dipping were demonstrated at all disinfectant concentrations for total aerobes (82.9 to 90.7%), Escherichia coli (99.4 to 99.6%), and total coliforms (86.1 to 98.5%) . Additionally, testing showed that ASC solutions maintained stable pH and minimal chlorite ion concentration deviations throughout each treatment . The results of the parameter evaluations indicated that maximal antimicrobial activity was achieved in carcasses that were prewashed and then exposed to a 5-s dip in a solution containing phosphoric acid- or citric acid-activated ASC . At 1,200 ppm ASC, a mild but transitory whitening of the skin was noted on dipped carcasses . The results support the methods currently approved by the U.S . Department of Agriculture for the use of ASC solutions as a prechill antimicrobial intervention in U.S . poultry processing plants. Intensive Care Med, 2000 Jun, 26(6), 808 - 12 Massive rhabdomyolysis and multiple organ dysfunction syndrome caused by leptospirosis; Coursin DB et al.; We report a case of leptospiral infection in a 63-year-old man who acquired the infection while swimming in canals and streams in Hawaii . The patient's course was atypical in that he was anicteric and had no evidence of meningitis when he presented with fever, rapidly progressive and severe rhabdomyolysis, thrombocytopenia, acute renal failure, and respiratory distress syndrome . Although he recovered after a protracted illness, he required major life support, including mechanical ventilation and hemodialysis . Initial antimicrobial therapy was designed to cover major bacterial and atypical pathogens, including leptospires . An in-depth work-up for causes of this catastrophic illness confirmed acute leptospirosis . Although rare, leptospirosis is a potentially lethal infection classically associated with hepatitis, azotemia, and meningitis . Most patients experience self-limited illness, with fever, myalgias, and malaise followed by an immune-mediated aseptic meningitis . A small proportion develop shock and multiple organ dysfunction . Whereas myalgias are ubiquitous in leptospiral infection, and most patients show mildly elevated muscle enzymes, life-threatening rhabdomyolysis is rare . This atypical case is reported to urge clinicians to consider leptospirosis in the evaluation of a patient with cryptogenic sepsis who develops multiple organ dysfunction associated with rhabdomyolysis . Appropriate antimicrobial therapy, with penicillin or doxycycline, can be life-saving. Intensive Care Med, 2000 Jun, 26(6), 704 - 15 Antithrombin III in patients with severe sepsis: a pharmacokinetic study; Ilias W et al.; OBJECTIVES: To evaluate the safety, pharmacokinetics, and the practicability of two different antithrombin III (AT III) high-dose regimens in patients with severe sepsis . DESIGN: Prospective, open, randomized, 2 parallel groups, multinational clinical trial . SETTING: Eleven academic medical center intensive care units (ICU) in Austria, Belgium, Denmark, Germany, Norway and Sweden . PATIENTS: Thirty-three patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III . INTERVENTIONS: Patients received an intravenous loading dose of 6,000 IU AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4 h or a continuous infusion of 250 IU AT III/h for 4 days, resulting in a total dose for both dosage regimens of 30,000 IU AT III . MEASUREMENTS: All patients were evaluated for safety and all but one for pharmacokinetics . RESULTS AND CONCLUSIONS: The administration of AT III was safe and well tolerated . The overall 28-day all-cause mortality was 30% (43% intermittent bolus infusions; 21% continuous infusion) . The mean probability of dying according to the SAPS II was 48% . The difference in mortality between both groups was within the range of chance . AT III plasma levels were elevated from low baseline levels to above 120% soon after onset of AT III therapy and remained at these levels for the treatment phase of 4 days . Functional and immunologic levels of AT III corresponded very well . With an overall median volume of distribution of 4.5 l (range: 2.4-6.5 l), AT III only moderately extended beyond plasma . The overall median elimination half-life was 18.6 h (range: 5.1-37.4) . Overall, median response was 1.75% per IU/kg (range: 1.14-2.8) . The variability of elimination parameters was quite noteworthy (CV = 41-59%), whereas distribution-related parameters showed a moderate variability (CV = 24%) . In spite of this variability, both high-dose IV regimens reliably provided AT III levels above 120% for all but one patient . An increased mortality was observed for patients with a distribution volume exceeding 4.5 l (or a response < 1.7% per IU/kg) . AT III distribution volumes above 4.5 l might indicate a capillary leak phenomenon . The continuous infusion regimen was slightly preferred by the investigators with regard to practicability. Kekkaku, 2000 Jul, 75(7), 477 - 82 {Changes in antibacterial activity of murine peritoneal macrophages against Mycobacterium tuberculosis after prolonged in vitro precultivation}; Akaki T et al.; We examined profiles of intramacrophagial growth of M . tuberculosis (MTB) when mouse peritoneal macrophages (M phi s) were infected with the organisms at day 0 or day 7 after in vitro precultivation, and obtained the following results . First, the growth rate of the virulent MTB H37Rv strain as well as attenuated H37Ra strain was slower in M phi s which had been precultured for 7 days (M phi s {day 7}) than in freshly prepared M phi s without precultivation (M phi s {day 0}) . The doubling time of MTB H37Rv was 2.2 and 2.9 days in M phi s {day 0} and M phi s {day 7}, respectively, and that of MTB H37Ra was 2.9 and 3.6 days in M phi s {day 0} and M phi s {day 7}, respectively . Second, MTB-mediated cytotoxicity in terms of the LDH release from infected M phi s was less marked in M phi s {day 7} than in M phi s {day 0}, when they were infected with MTB of either the H37Rv or H37Ra strain . MTB H37Ra strain exhibited much weaker cytotoxic effects on host M phi s than did H37Rv strain . Third, when M phi s {day 7} were infected with MTB of either the H37Rv or H37Ra strain, they showed markedly lowered levels of reactive oxygen intermediate (ROI) production than did M phi s {day 0} . In contrast, the reactive nitrogen intermediate (RNI) producing ability of M phi s in response to MTB infection was not so markedly reduced in M phi s {day 7} from that of M phi s {day 0} . As mentioned above, the M phi s {day 7} did not permit accelerated growth of infected MTB, compared to the MTB growth in the M phi s {day 0} . It thus appears that ROI played a trivial role in the antimicrobial activity against MTB of murine peritoneal M phi s which had been precultured for long periods . Although it is regarded that RNI played more critical roles in M phi anti-MTB activity than did ROI, the present results also suggest that other kinds of antimicrobial effectors are required in M phi antimicrobial activity against MTB organisms, particularly in the case of M phi s after prolonged in vitro cultivation. Biochem Biophys Res Commun, 2000 Aug 18, 275(1), 69 - 74 Characterization of p40/GPR69A as a peripheral membrane protein related to the lantibiotic synthetase component C; Bauer H et al.; The 40 kDa erythrocyte membrane protein p40/GPR69A, previously assigned to the G-protein-coupled receptor superfamily, was now identified by peptide-antibodies and characterized as a loosely associated peripheral membrane protein . This result is in striking contrast to the proposed seven-transmembrane protein structure and function and therefore we wish to correct our previous proposal . p40 is located at the cytoplasmic side of the membrane and is neither associated with the cytoskeleton nor lipid rafts . Refined sequence analysis revealed that p40 is related to the LanC family of bacterial membrane-associated proteins which are involved in the biosynthesis of antimicrobial peptides . Therefore, we rename p40 to LanC-like protein 1 (LANCL1) and suggest that it may play a similar role as a peptide-modifying enzyme component in eukaryotic cells . Nitric Oxide, 2000 Aug, 4(4), 423 - 30 Nitric oxide involvement in Drosophila immunity; Nappi AJ et al.; The augmented production of nitric oxide (NO) was observed during the hemocyte-mediated melanotic encapsulation responses of Drosophila melanogaster and D . teissieri . When introduced into the hemocoel of D . melanogaster larvae, NO activated the gene encoding the antimicrobial peptide Diptericin . These observations, together with previous studies documenting the production of superoxide anion (O(*-)(2)) and H(2)O(2) in immune-challenged Drosophila, provide evidence that reactive intermediates of both oxygen (ROI) and nitrogen (RNI) constitute a part of the cytotoxic arsenal employed by Drosophila in defense against both microbial pathogens and eukaryotic parasites . These ROI and RNI appear to represent an evolutionarily conserved innate immune response that is mediated by regulatory proteins that are homologous to those of mammalian species . Indian J Med Res, 2000 May, 111, 168 - 71 Evaluation of E test for susceptibility testing of Mycobacterium tuberculosis to primary anti tubercular drugs; Kakkar N et al.; BACKGROUND & OBJECTIVES: Antimicrobial susceptibility tests for tuberculosis take weeks and delayed therapy can lead to an increase in disease incidence . The E test is a new concept for minimum inhibitory concentrations (MIC) determinations for antimicrobial agents that is based on a predefined antibiotic gradient on a plastic strip calibrated with a continuous logarithmic MIC scale covering 15 two-fold dilutions . The present study was undertaken to evaluate E test strips for susceptibility testing of Mycobacterium tuberculosis . METHODS: Twenty five clinical isolates of M . tuberculosis were tested for the four first line antitubercular drugs by E test and were compared with standard proportion method . The inoculum turbidity was adjusted to McFarland 3.0 standard and agar plates (Middle brook 7H11 agar) were inoculated and preincubated (37 degrees C in 7-10% CO2) for 24 h after which time, the E test strips were placed on the agar surface which were incubated under same conditions . The MIC was interpreted as the point at which the ellipse intersected the 'E test' strip as described in E test technical guide . RESULTS: Of the 25 strains, susceptibility as determined by both methods for isoniazid (INH), rifampin, ethambutol and streptomycin was found in 22 (88%), 20 (80%), 24 (96%) and 18 (72%) strains respectively . Agreement between E test and proportion method was 96 per cent for INH, 92 per cent for rifampin and 100 per cent for ethambutol and streptomycin each . However, sensitivity could be predicted after 7-10 days by E test and exact MIC could also be determined . INTERPRETATION & CONCLUSIONS: E test method was found to be rapid, accurate, reliable and easy to perform . It can be employed for routine susceptibility testing for antitubercular drugs. J Biol Chem, 2000 Oct 27, 275(43), 33464 - 70 Isolation and characterization of gomesin, an 18-residue cysteine-rich defense peptide from the spider Acanthoscurria gomesiana hemocytes with sequence similarities to horseshoe crab antimicrobial peptides of the tachyplesin family; Silva PI Jr et al.; We have purified a small size antimicrobial peptide, named gomesin, from the hemocytes of the unchallenged tarantula spider Acanthoscurria gomesiana . Gomesin has a molecular mass of 2270.4 Da, with 18 amino acids, including a pyroglutamic acid as the N terminus, a C-terminal arginine alpha-amide, and four cysteine residues forming two disulfide bridges . This peptide shows marked sequence similarities to antimicrobial peptides from other arthropods such as tachyplesin and polyphemusin from horseshoe crabs and androctonin from scorpions . Interestingly, it also shows sequence similarities to protegrins, antimicrobial peptides from porcine leukocytes . Gomesin strongly affects bacterial growth, as well as the development of filamentous fungi and yeast . In addition, we showed that gomesin affects the viability of the parasite Leishmania amazonensis. J Infect, 2000 Jul, 41(1), 73 - 83 Assessment of antibiotic prescription in acute respiratory infections in adults . The Spanish Study Group on Antibiotic Treatments; Ochoa C et al.; OBJECTIVE: This study aims to ascertain the variability in the use of antibiotics for the treatment of acute respiratoryinfections in several hospital emergency services in Spain, as well as the appropriateness of antibiotics prescription through evaluation by a panel of experts using available scientific evidence . METHOD: A cross-sectional study was carried out in the emergency services of 10 hospitals in different Spanish regions . We chose patients diagnosed as having acute respiratory infection, aged over 14 years . Among the collected variables were: type of respiratory infection, antibiotic prescription, comorbidity, qualification of the prescribing doctor and hospital admission . The consensus conference held by a panel of experts established first choice treatment and the alternative and inappropriate use for each respiratory infection, based on the available scientific evidence . All the observed prescriptions in our study were classified according to this pattern . RESULTS: A sample of 2899 acute respiratory infections was studied (5.5% of all emergencies) . Antibacterial agent treatment was prescribed in 82.6% of these, varying according to the infection between 98.5% of pneumonias and 49% of croup-influenza-common cold . The most commonly used antibiotics were amoxicillin-clavulanate and cefuroxime . The global percentage of inappropriate prescription was 40.5% (95% CI; 35.4-45.5) . The prescriptions were inappropriate in 16.9% of cases of pharyngotonsillitis, 17.8% of chronic bronchitis, 26.9% of acute bronchitis, 29.3% of pneumonias, 30.8% of otitis and sinusitis and in 70.8% of croup, flu, common cold and non-specified infections . Significant variability among participating centres was observed, both in choice of antibiotics and in their degree of appropriateness . CONCLUSIONS: There is excessive use of antimicrobial drugs in acute respiratory infections, and the majority are used for viral infections . There is indiscriminate use of broad spectrum antibiotics, which are valid in some infections but clearly inappropriate in others . Similarly, there are important differences in the choice of antibiotics and their degree of appropriateness among hospitals . Can J Microbiol, 2000 Aug, 46(8), 692 - 9 Effects of the Fusarium spp . mycotoxins fusaric acid and deoxynivalenol on the growth of Ruminococcus albus and Methanobrevibacter ruminantium; May HD et al.; The Fusarium spp . mycotoxins fusaric acid and deoxynivalenol (DON) were tested for antimicrobial activity against Ruminococcus albus and Methanobrevibacter ruminantium . The growth of both organisms was inhibited by fusaric acid as low as 15 micrograms/mL (84 microM) but not by DON, at levels as high as 100 micrograms/mL (338 microM) . No synergistic inhibitory effect was observed with DON plus fusaric acid . Neither organism was able to adapt to the fusaric acid and responses of each organism to the compound were different . The optical density (OD) maximum for R . albus, but not for M . ruminantium, was diminished after 28 days incubation at concentrations of fusaric acid below 240 micrograms/mL . Inhibition of R . albus started before significant growth had occurred, while M . ruminantium doubled twice before the onset of inhibition . Responses to picolinic acid, an analog of fusaric acid, were also dramatically different between the two microorganisms with M . ruminantium exhibiting a severe lag followed by a complete recovery of growth, while R . albus was only slightly inhibited with no lag . These results suggest that the mechanism of fusaric acid inhibition is specific to each microorganism . This is the first demonstration of the common mycotoxin fusaric acid inhibiting the growth of rumen bacteria. Ned Tijdschr Geneeskd, 2000 Jul 29, 144(31), 1474 - 80 {Immunology in the medical practice . XXXI . Hereditary immune deficiencies: relationship between clinical symptoms and abnormalities of the immune system}; Vossen JM et al.; Severe congenital immunodeficiency diseases occur in approximately 1:10,000 newborns, in Western Europe and North America . They are characterised by recurrent infections, mostly caused by opportunistic micro-organisms, and autoimmune phenomena . In many patients the immune deficiency occurs as part of a syndrome . An immunological dysfunction may be caused by total absence, strong reduction or dysfunction of one or more cellular elements or of cell-associated or cellular secretion products . It is convenient to divide the immune system into a cellular compartment (with specific T and B cells, and non-specific natural killer cells and myelomonocytes), a compartment for cellular interactions (adhesion, costimulation and communication through cytokines) and an aspecific opsonization compartment . In cases of deficient humoral immunity treatment options are antimicrobial drugs and substitution therapy with immunoglobulins, in cases of phagocytic dysfunction the application of intracellularly active antibiotics and in cases of disturbances of cellular immunity allogeneic transplantation of haematopoietic stem cells and in the future perhaps the repair of the genetic defect by somatic gene therapy. J Ethnopharmacol, 2000 Aug, 71(3), 365 - 76 The efficiency of random versus ethno-directed research in the evaluation of Sinai medicinal plants for bioactive compounds; Khafagi IK et al.; Hexane, ethyl acetate and ethanol extracts of sixty plant species (growing wild in Sinai, Egypt) were screened for