Bactericidal

J Anim Sci, 1998 Jan, 76(1), 118 - 23
Tribasic copper chloride and copper sulfate as copper sources for weanling pigs; Cromwell GL et al.; We conducted three 28-d experiments involving a total of 915 pigs to assess the relative efficacy of tribasic Cu chloride (Cu2{OH}3Cl) and Cu sulfate pentahydrate (CuSO4.5H20) in diets for weanling pigs . Experiments 1 and 2 were conducted at an experiment station (University of Kentucky), and Exp . 3 was conducted at a commercial feed company's swine research facilities (United Feeds, Inc.) . The basal diet was a fortified corn-soybean meal-dried whey diet (1.25% lysine) with no antimicrobials in Exp . 1 or with carbadox (55 mg/kg) in Exp . 2 and 3 . In Exp . 1, 135 pigs were weaned at 27 to 31 d and fed the basal diet without or with 100 or 200 ppm Cu from Cu chloride, or 100 or 200 ppm Cu from Cu sulfate from 7.9 to 17.7 kg BW . The 200 ppm level of Cu from Cu sulfate improved ADG (P < .10), and both levels of Cu from Cu chloride tended to improve feed:gain . In Exp . 2, 150 pigs were weaned at 27 to 31 d and fed the basal diet without or with 100, 150, or 200 ppm Cu from Cu chloride, or 200 ppm Cu from Cu sulfate from 8.9 to 20.8 kg BW . Addition of 200 ppm Cu improved ADG (P < .08) and ADFI (P < .01), but not feed:gain . Source of Cu did not affect performance . In Exp . 3, 630 pigs were weaned at 16 to 20 d and fed a common diet for 10 to 12 d until the start of the experimental period . The same experimental diets as used in Exp . 2 were fed from 9.1 to 25.5 kg BW . Both Cu sources improved ADG (P < .01), and sources and levels of Cu did not differ . Liver Cu increased in pigs fed 200 ppm Cu, and Cu sulfate tended to increase liver Cu more than did Cu chloride in one experiment, but not in another experiment . The results indicate that tribasic Cu chloride is as effective as Cu sulfate in improving growth in weanling pigs.

J Anim Sci, 1998 Jan, 76(1), 287 - 98
Liver abscesses in feedlot cattle: a review; Nagaraja TG et al.; Liver abscesses in slaughtered beef cattle result from aggressive grain-feeding programs . The incidence, averaging from 12 to 32% in most feedlots, is influenced by a number of dietary and management factors . Liver abscesses represent a major economic liability to producers, packers, and ultimately consumers . Besides liver condemnation, economic impacts include reduced feed intake, reduced weight gain, decreased feed efficiency, and decreased carcass yield . Fusobacterium necrophorum, a member of the ruminal anaerobic bacterial flora, is the primary etiologic agent . Actinomyces pyogenes is the second most frequently isolated pathogen . Ruminal lesions resulting from acidosis generally are accepted as the predisposing factors for liver abscesses . F . necrophorum possesses or produces a number of virulence factors that participate in the penetration and colonization of the ruminal epithelium and subsequent entry and establishment of infection in the liver . However, only a few virulence factors have been characterized well . Control of liver abscesses in feedlot cattle generally has depended on the use of antimicrobial compounds . Five antibiotics (i.e., bacitracin methylene disalicylate, chlortetracycline, oxytetracycline, tylosin, and virginiamycin) are approved for prevention of liver abscesses in feedlot cattle . Tylosin is the most effective and the most commonly used feed additive . Tylosin feeding reduces abscess incidence by 40 to 70% . The mode of action of antibiotics in preventing liver abscesses is believed to be via inhibition of ruminal F . necrophorum . Protective immunity against F . necrophorum induced by a variety of antigenic components has ranged from ineffectual to significant protection.

Soc Sci Med, 1998 Jan, 46(1), 29 - 38
An economic perspective on policy to reduce antimicrobial resistance; Coast J et al.; Resistance to antimicrobial drugs is increasing worldwide . This resistance is, at least in part, associated with high antimicrobial usage . Despite increasing awareness, economists (and policy analysts more generally) have paid little attention to the problem . In this paper antimicrobial resistance is conceptualised as a negative externality associated with the consumption of antimicrobials and is set within the broader context of the costs and benefits associated with antimicrobial usage . It is difficult to determine the overall impact of attempting to reduce resistance, given the extremely limited ability to model the epidemiology of resistant and sensitive micro-organisms . It is assumed for the purposes of the paper, however, that dealing with resistance by reducting antimicrobial usage would lead to a positive societal benefit . Three policy options traditionally associated with environmental economics (regulation, permits and charges) are examined in relation to their potential ability to impact upon the problem of resistance . The primary care sector of the U.K.'s National Health Service provides the context for this examination . Simple application of these policies to health care is likely to be problematic, with difficulties resulting particularly from the potential reduction in clinical freedom to prescribe when appropriate, and from the desire for equity in health care provision . The paper tentatively concludes that permits could offer the best policy response to antimicrobial resistance, with the caveat that empirical research is needed to develop the most practical and efficient system . This research must be conducted alongside the required epidemiological research.

Mol Immunol, 1997 Aug-Sep, 34(12-13), 839 - 42
Complete nucleotide sequence of human NRAMP2 cDNA; Kishi F et al.; The mouse Lsh/Ity/Bcg locus regulates macrophage activation for antimicrobial activity against intracellular pathogens, and the Nramp1 gene was isolated as its candidate . In the present study, a full length cDNA for human NRAMP2 has been isolated and characterized . Nucleotide sequence analysis reveals that the cDNA, 4142 bp in length, coded for a protein of 561 amino acid residues with a molecular weight mass of 61,456 . Predicted amino acid sequence analysis of the NRAMP2 molecule indicates that NRAMP1 and NRAMP2 sequences share 64% identical residues overall, whereas only 21% at the NH2-terminal cytoplasmic domain, where the NRAMP1 molecule was associated with microtubules, was found to be identical . This suggests that the NH2-terminal region of the NRAMP2 molecule may have a particular function, different from that of the NRAMP1 molecule.

Biochem Biophys Res Commun, 1998 Jan 26, 242(3), 608 - 12
Expression of antimicrobial peptides has an antitumour effect in human cells; Winder D et al.; The antimicrobial peptides cecropin and melittin are known to exhibit antitumour activity in tumour derived cell lines . To achieve a similar effect in vivo these peptides would have to be given repeatedly to maintain therapeutic levels, which may be pharmacologically unfavourable . The expression of the genes encoding such antimicrobial peptides in the desired cell type may circumvent these problems . Expression constructs carrying cecropin or melittin have been introduced into a human bladder carcinoma derived cell line and the resultant cell clones analysed for tumorigenicity in nude mice . Expression of cecropin resulted in either a complete loss of tumorigenicity in some clones or reduced tumorigenicity, as measured by latency of tumour formation . These results suggest that vector mediated delivery of this gene to tumour cells may prove useful for cancer gene therapy.

Trans R Soc Trop Med Hyg, 1997 Sep-Oct, 91(5), 599 - 601
Oral fluoroquinolones for maintenance treatment of melioidosis; Chaowagul W et al.; Ciprofloxacin (20 mg/kg/d) or ofloxacin (12 mg/kg/d) given for a median of 15 weeks (range 12-40) were used for maintenance treatment of 57 adult patients with melioidosis . The median duration of follow-up in the 45 patients who complied with treatment and were followed for at least 6 months was 28 months (range 6-65) . Fluoroquinolone treatment was well tolerated . There were 13 treatment failures (5 failures to respond, 8 relapses), a failure rate of 29% (95% confidence interval 17-43%) . The median time to treatment failure was 7 months (range 2-26) . These results are inferior to those with courses lasting 20 weeks of amoxycillin/clavulanic acid or the combination of chloramphenicol, doxycycline and trimethoprim/sulphamethoxazole, and suggest that the fluoroquinolones should be reserved as third line agents, and not used for the maintenance treatment of melioidosis unless there is resistance to, or intolerance of, the other available antimicrobial compounds.

Hepatology, 1998 Feb, 27(2), 533 - 6
The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure; Kaita KD et al.; Recently, we reported that ciprofloxacin, an antimicrobial agent with gamma-aminobutyric acid (GABA(A)) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis . In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats . One hundred nineteen adult, male Sprague-Dawley rats (n = 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 micromol/kg), a potent hepatic growth promoter . Mortality rates were then documented over a 4-day period . An additional 45 rats (n = 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 micromol/kg) . In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining . In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P < .05) . Survival figures in the norfloxacin- and putrescine-treated groups were not significantly improved (15% and 25%, respectively) . In the regeneration study, compared with the D-gal + saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal + ciprofloxacin and D-gal + putrescine groups (10.2 +/- 3.3 vs . 18.2 +/- 5.1 and 18.8 +/- 6.8 x 10(3) dpm/mg DNA respectively; P < .05) . The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 +/- 3.7; ciprofloxacin, 47.4 +/- 7.3; and putrescine, 8.4% +/- 2.8% hepatocytes staining positive) . Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.

J Antimicrob Chemother, 1997 Dec, 40(6), 881 - 3
In-vitro susceptibility of Helicobacter pylori to ampicillin, clarithromycin, metronidazole and omeprazole; Loo VG et al.; The in-vitro activities of omeprazole and three antimicrobial agents against 89 clinical isolates of Helicobacter pylori from a population with duodenal ulcer disease were determined by an agar dilution method . Resistance rates were 20% for metronidazole (MIC > 8 mg/L), 1% for clarithromycin (MIC > 2 mg/L) and zero for ampicillin (MIC > 8 mg/L) . Omeprazole was relatively active against H . pylori in vitro (MIC < or = 8 mg/L).

J Antimicrob Chemother, 1997 Dec, 40(6), 779 - 88
Therapy of deep fungal infection in haematological malignancy . Working Party of the British Society for Antimicrobial Chemotherapy; Diagnosis of late onset neonatal sepsis with cytokines et al.; Department of Paediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, New Territories Hong Kong, People's Republic of ChinaAIMS: To evaluate the commonly used markers--namely IL-6, TNF alpha, IL-1 beta, C-reactive protein and E-selection for identification of late onset neonatal sepsis; to define the optimal cutoff value for each marker in preterm neonates; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases; and to delineate the profile of these markers during systemic infection and in relation to successful treatment . METHODS: Very low birthweight infants in whom clinical sepsis was suspected when they were > 72 hours of age were eligible for study . A full sepsis screen was performed in each episode . Cytokines, C-reactive protein, and E-selectin were serially measured on days 0 (at the time of sepsis evaluation), 1, 2, 4 and 7 . The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1 . The sensitivity, specificity, positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined . RESULTS: One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants . Forty five episodes were proved to be infections . The optimal cutoff values were IL-6 31 pg/ml, TNF alpha 17 pg/ml, IL-1 beta 1 pg/ml, C reactive protein 12 mg/l and E-selectin 174 ng/ml . IL-6 had the highest sensitivity (89%) and negative predictive value (91%) for detecting late onset infection on day 0 . However, between 24 and 48 hours of onset, C-reactive protein was the best single marker, with an overall sensitivity and specificity of 84% and 96%, respectively . The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests . Performing IL-6 and C-reactive protein on day 0, together with either TNF alpha on day 1 or C-reactive protein on day 2, showed the best overall sensitivity (98%) and specificity (91%) for the diagnosis of late onset infection . CONCLUSIONS: Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined . Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended, but the concomitant use of IL-6 and C-reactive protein or TNF alpha should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results, provided that the infants are in good clinical condition.

J Nat Prod, 1998 Jan, 61(1), 122 - 5
Novel bromopyrrole alkaloids from the sponge Agelas dispar; Cafieri F et al.; Further investigation of the Caribbean marine sponge Agelas dispar for biologically active constituents has led to the isolation of the novel bromopyrrole alkaloids longamide B (1), and clathramides C (2) and D (3), whose structures have been determined by spectroscopic methods . Isolation of the known keramadine (4) and of the ecdysonic sterols ecdysterone (5) and ajugasterone C (6) is also reported . The antimicrobial activities of the isolated bromopyrrole alkaloids is summarized.

Gene, 1998 Jan 5, 206(1), 85 - 91
Localization and genomic organization of sheep antimicrobial peptide genes; Huttner KM et al.; Antimicrobial peptides are an abundant and diverse component of animal innate immunity . Within mammalian species, defensins and cathelicidins are the two principal antimicrobial peptide families . We identified and sequenced ten new sheep genes which encode potential antimicrobial peptides including two beta-defensins and eight cathelicidins . We mapped the two-exon beta-defensin genes to sheep chromosome 26 and the four-exon cathelicidin genes to sheep chromosome 19 using sheep-hamster somatic cell hybrids in conjunction with flow-sorted sheep chromosomes . These assignments confirm homology between sheep, cattle, mouse, and human antimicrobial peptide gene families . Contig construction for the sheep cathelicidin gene family demonstrates that three genes, OaDodeA, OaDodeB, and OaMAP-34, are present head-to-tail in a 14.5 kb region, and that four proline/arginine-rich genes, OaBac5, OaBac7.5, OaBac11, and OaBac6, are arranged head-to-tail in a region covering 30.5 kb . This richly diverse family of sheep cathelicidin peptides is encoded in a gene array which may reflect the mechanism of its evolution.

J Infect, 1997 Nov, 35(3), 311 - 3
Cerebral nocardia abscesses in a patient with AIDS: correlation of magnetic resonance and white cell scanning images with neuropathological findings; Ogg G et al.; We present a case of cerebral nocardiosis in a patient with AIDS . Space-occupying lesions were identified using magnetic resonance imaging (MRI) and white cell scanning . Nocardia asteroides was isolated from blood cultures . The patient's response to treatment with amikacin, imipenem and ceftriaxone was followed clinically and radiologically . When he died 6 months later, N . asteroides was isolated at post-mortem from a cerebral abscess . Although cerebral infections associated with the infiltration of neutrophils are rare in patients with AIDS, this case demonstrates that indium-labelled neutrophils can be used to identify a brain abscess and monitor its response to antimicrobial therapy.

Int J Tuberc Lung Dis, 1997 Jun, 1(3), 270 - 5
Electron microscopic analysis of Mycobacterium avium complex isolates exposed to ciprofloxacin, rifabutin, ethambutol and clarithromycin; Reisner BS et al.; SETTING: Mycobacterium avium complex (MAC) isolates grown in the presence of clarithromycin, ciprofloxacin, ethambutol or rifabutin were examined by electron microscopy for drug-induced ultrastructural changes . OBJECTIVE: To further the understanding of the activity of clarithromycin, ciprofloxacin, ethambutol and rifabutin against MAC . DESIGN: Four MAC isolates, 1 control and 3 patient, were cultured for 24 or 72 hours in liquid medium containing one of two concentrations of an antimicrobial agent prior to examination by electron microscopy . RESULTS: One or more of the following ultrastructural changes was observed after exposure to the antimicrobial agent: disorganized nucleoid and cytoplasm, condensation of nucleoid, vacuolization, enlargement of the periplasmic space with or without vesicles, intracytoplasmic lipid-like inclusions, and cell lysis . Changes were seen after as little as 24 hours of exposure to the antimicrobial agent and were more evident with the higher of the two concentrations of the drug . Changes were present regardless of the minimum inhibitory concentration (MIC) of the antimicrobial agent against the isolates tested, but were more pronounced if the MIC was less than the concentration of drug tested . CONCLUSION: Consistent ultrastructural changes were observed following exposure to a given antimicrobial agent . No drug-specific changes were identified.

Helicobacter, 1997 Jul, 2 Suppl 1, S89 - 91
Is the only good Helicobacter a dead Helicobacter?
Misiewicz JJ.
BACKGROUND: Vast numbers of therapeutic studies of various drug regimens used for the cure of H . pylori infection have been published . However, many of these studies have been uncontrolled, included small numbers of patients, were published only as abstracts, differed widely in dosage sizes, schedules and durations and were of insufficient statistical power to make meaningful statements concerning their efficacy . Furthermore, there are no clear or universally accepted guidelines for the treatment of H . pylori infection . Thus, there remains profound confusion among practitioners on whom and how to treat . OBJECTIVE: To critically review the currently available management strategies for H . pylori infection . METHODS: Review of the literature . RESULTS: Treatment of H . pylori requires the use of multiple drug regimens (triple therapy) which can be expensive and is often associated with side effects . Bad choice of treatments, poor patient counseling and compliance will lead to the emergence of resistant H . pylori strains . Resistance to H . pylori to metronidazole is already widespread and resistance to other antimicrobial agents is increasing . The resource/financial implications are not negligible . CONCLUSIONS: The introduction of kits that will enable the identification of pathogenic strains of H . pylori in the office setting may decrease the number of patients being given H . pylori eradication therapy, but much more evidence is needed to establish the practical value of such tests . In the meantime, as many clinicians adhere to the idea that the only good H . pylori is a dead H . pylori, the best practical policy option is education concerning the correct diagnostic methodology, correct choice of patients and the correct choice of treatment regimens . The discovery of Helicobacter pylori (H . pylori) has revolutionized our concepts of etiology, pathophysiology and treatment of many foregut diseases . Gastritis, gastric ulcer (GU), duodenal ulcer (DU), gastric cancer, MALT gastric lymphoma and other conditions are now regarded as being independent on the colonization of the stomach by H . pylori . Many aspects of pathophysiology, such as the abnormalities of gastric acid secretion in duodenal ulcer disease, now for the first time fall into a logical and comprehensible pattern.

Helicobacter, 1997 Sep, 2(3), 144 - 8
Relationship between the efficacy of amoxicillin and intragastric pH for the treatment of Helicobacter pylori infection; Kleveland PM et al.; BACKGROUND: Proton pump inhibitors are reported to enhance the efficacy of antibiotics in the treatment of Helicobacter pylori infection . An elevated intragastric pH is considered to be an important factor for this increased antimicrobial efficacy . The aim of this study was to assess the effect of different doses of lansoprazole on 24-hour intragastric pH and to correlate the effect of amoxicillin on the cure rate for H . pylori infection with the intragastric pH obtained during lansoprazole treatment . PATIENTS AND METHODS: Thirty-six duodenal ulcer patients who tested positively for H . pylori as assessed by a rapid urease test, culture, and histological evaluation were allocated randomly to dual treatment with amoxicillin, 3 gm/day, and lansoprazole in different doses ranging between 30 and 180 mg/day for 2 weeks . A 24-hour intragastric pH measurement was taken in all patients on the fifth day of treatment . H . pylori status was determined by culture and histological workup 6 weeks after cessation of the amoxicillin-lansoprazole medication . RESULTS: The H . pylori infection was treated successfully in 19 of 32 patients who completed the dual therapy (per protocol, 59.4%) . The median intragastric pH in patients who were treated successfully was 4.4 (95% confidence interval {CI} = 3.7-4.7), as compared to 4.0 (95% CI = 3.5-4.5) in patients who were not treated successfully (p = .47, Wilcoxon's rank sum test) . The median percentage of time that the intragastric pH exceeded 4 was not different in the two groups (p = .77) . Administration of lansoprazole in doses exceeding 30 mg induced only a moderate additional increase in intragastric pH . CONCLUSIONS: Profound inhibition of gastric acid secretion seems not to be necessary to improve the effect of amoxicillin on the cure rate for H . pylori infection in patients with duodenal ulcers.

Hematol Cell Ther, 1997 Oct, 39(5), 269 - 73
{Antiviral immunodeficiency: EBV, CMV, adenovirus}; Cavazzana-Calvo M et al.; Patients undergoing bone marrow transplantation are susceptible to many different bacterial, fungal and viral infections . Among the viral pathogens, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus cause the greatest morbidity and mortality and have been the most common infectious causes of death following the grafting of allogeneic marrow . This great susceptibility to viral infections is due to the immunodeficiency in cellular and humoral immune responses lasting for months to years . Contributing factors are high-dose chemo/radiotherapy, graft-versus-host disease (GVHD) prophylaxis/treatment, GVHD itself, the degree of HLA disparity between donor and recipient and the underlying disease . Defects of T cell helper and cytotoxic functions contribute to the great incidence of viral infections . We described here the kinetic of immunological reconstitution and the role of T cell immunodeficiency . At day 30 to 40 after BMT, a minority of patients had recovery of virus-specific CD8+ T-cell response . Between day 40 and day 90 recovery of deficient CD8+ and CD4+ T cell responses occurred in the majority of the recipients of HLA identical BMT but only in the minority of the recipients of HLA partially incompatible BMT . New approaches should therefore be envisaged either to preserve donor T-cell-mediate immunity or tho accelerate immune reconstitution . Add-back of unmanipulated T-cells, or virus-specific T cells could improve antimicrobial defenses after BMT.

J Clin Microbiol, 1998 Jan, 36(1), 302 - 4
Evaluation of the BIOMIC video reader system for determining interpretive categories of isolates on the basis of disk diffusion susceptibility results; Korgenski EK et al.; The BIOMIC System (Giles Scientific, New York, N.Y.) includes software and a video-assisted plate reader that functions with a personal computer to automate, speed read, and interpret standard antibiotic disk diffusion test plates . The video reader helps standardize endpoints, speeds quantitative measurements by 40 to 90%, and reduces fatigue and transcription and interpretation errors (H . Wei-Fang, Am . Clin . Lab . 13:28-29, 1994) . Organisms tested were isolated from patient specimens collected at Primary Children's Medical Center and included rapidly growing gram-positive and gram-negative strains that fulfill the National Committee for Clinical Laboratory Standards guidelines for disk diffusion susceptibility testing . A comparison of the plate reader-determined zones and visually measured zones for 3,339 organism-antimicrobial agent combinations was performed . The results demonstrated 0.1% (4 of 3,339) false-susceptible reads and 0.2% (6 of 3,339) false-resistant reads by the video reader compared with visual reads . Minor discrepancies (4.7% {156 of 3339}), resulting in category interpretation changes of intermediate to resistant or susceptible or changes of resistant or susceptible to intermediate, were also encountered . Of the discrepant results, 80.8% (139 of 172) resulted from a 3-mm or less zone diameter difference between the two different techniques . We conclude that the video-assisted plate reader is a reliable system for determining interpretative categories from zone diameters of standard antibiotic disk diffusion test plates.

Oral Oncol, 1997 Sep, 33(5), 322 - 6
Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation; Bondi E et al.; The present investigation has examined the clinical benefits of tobramycin, polymyxin E and amphotericin therapy in the management of oral mucositis in children undergoing chemotherapy prior to bone marrow transplantation . Tobramycin, polymyxin E, and amphotericin reduced the degree of oral mucositis more than conventional therapy of diphenhydramine, Maalox, and local analgesic . While there was a statistically significant fall in the severity of the mucositis with tobramycin, polymyxin E and amphotericin, this was unlikely to be of practical benefit.

Mol Med Today, 1995 Jul, 1(4), 174 - 80
Generation and utilization of synthetic combinatorial libraries; Eichler J et al.; The use of combinatorial chemistry is fundamentally changing the pace and scope of basic research and drug discovery . Since the introduction of synthetic peptide libraries several years ago, combinatorial chemistry has proven to be a powerful tool for the generation of immense molecular diversities of peptides, peptidomimetics and new organic compounds . This article briefly reviews methods for the generation and application of combinatorial libraries, with particular emphasis on soluble synthetic combinatorial libraries . The utility of these molecular diversities for basic research and drug discovery has been demonstrated through the identification of numerous highly active compounds such as antigenic peptides, receptor ligands, antimicrobial compounds and enzyme inhibitors.

J Biol Chem, 1997 Dec 12, 272(50), 31609 - 16
Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis; Ghosh JK et al.; The antimicrobial activity of various naturally occurring microbicidal peptides was reported to result from their interaction with microbial membrane . In this study, we investigated the cytotoxicity of the hemolytic peptide dermaseptin S4 (DS4) and the nonhemolytic peptide dermaseptin S3 (DS3) toward human erythrocytes infected by the malaria parasite Plasmodium falciparum . Both DS4 and DS3 inhibited the parasite's ability to incorporate {3H}hypoxanthine . However, while DS4 was toxic toward both the parasite and the host erythrocyte, DS3 was toxic only toward the intraerythrocytic parasite . To gain insight into the mechanism of this selective cytotoxicity, we labeled the peptides with fluorescent probes and investigated their organization in solution and in membranes . In Plasmodium-infected cells, rhodamine-labeled peptides interacted directly with the intracellular parasite, in contrast to noninfected cells, where the peptides remained bound to the erythrocyte plasma membrane . Binding experiments to phospholipid membranes revealed that DS3 and DS4 had similar binding characteristics . Membrane permeation studies indicated that the peptides were equally potent in permeating phosphatidylserine/phosphatidylcholine vesicles, whereas DS4 was more permeative with phosphatidylcholine vesicles . In aqueous solutions, DS4 was found to be in a higher aggregation state . Nevertheless, both DS3 and DS4 spontaneously dissociated to monomers upon interaction with vesicles, albeit with different kinetics . In light of these results, we propose a mechanism by which dermaseptins permeate cells and affect intraerythrocytic parasites.

Chem Biol, 1995 Mar, 2(3), 147 - 56
Netropsin and spermine conjugates of a water-soluble quinocarcin analog: analysis of sequence-specific DNA interactions; Flanagan ME et al.; BACKGROUND: Quinocarcin is the simplest of the bioxalmycin/naphthyridinomycin/tetrazomine/saframycin class of anti-tumor antibiotics, which damage DNA in a process that is inhibited by superoxide dismutase (SOD) . The oxazolidine moiety of this class of anti-tumor antibiotics undergoes a redox self-disproportionation reaction of the Cannizzaro type . The reaction is proposed to proceed via an intermediate carbon-centered radical, which then reduces molecular oxygen to give superoxide . We set out to determine whether the DNA-cleavage properties of these anti-tumor antibiotics could be retained in less complex analogs of quinocarcin . RESULTS: A totally synthetic, water-soluble analog of quinocarcin has been prepared . This analog produced superoxide, but had considerably reduced ability to cleave supercoiled circular DNA compared to quinocarcin or tetrazomine . When conjugated to the DNA-binding molecule spermine, however, it cleaved DNA as effectively as quinocarcin at less than 1/10 the concentration . A conjugate with netropsin displayed selective cleavage around the sequence 5'-d(ATTT)-3' . Molecular modeling of the interaction between the conjugate and DNA, together with the pattern of cleavage, indicates that a non-diffusable oxidant is involved in sequence-selective DNA cleavage . The spermine conjugate displayed weak antimicrobial activity . CONCLUSIONS: Knowledge of the stereoelectronic requirements for superoxide production by quinocarcin has allowed us to design a structurally less complex analog which has many of the same physical properties, including water solubility, the ability to produce superoxide and the ability to cleave DNA . Covalently attaching known DNA-binding molecules to this analog gave a compound that produced sequence-specific DNA damage . Our results suggest that a mechanism other than superoxide production can mediate DNA damage by the netropsin conjugate.

Prikl Biokhim Mikrobiol, 1997 Jul-Aug, 33(4), 428 - 32
{Preparation of films with combined biological activity and study of their properties}; Virnik AD et al.; Joint immobilization of a proteolytic enzyme (terrilytin, protease C, or collytin) and an antimicrobial compound or the bacteriolytic enzyme lysozyme in the structure of polyvinyl alcohol was studied . Changes in the activity of immobilized enzymes upon x-ray sterilization were studied . These materials were highly effective in wound healing.

Lik Sprava, 1996 May-Jun, (5-6), 106 - 8
{The effect of hypotensive therapy on external respiratory function in patients with chronic obstructive bronchitis}; Maev IV et al.; Values for the function of external respiration are submitted as are hemodynamic indices in patients with chronic obstructive bronchitis concurrent with arterial hypertension, who had not only been administered antimicrobial, anti-inflammatory and bronchoispasmolytic therapies but also received hypotensive agents in different doses . Effects of the latter on results of a multimodality treatment were studied.

Clin Microbiol Rev, 1998 Jan, 11(1), 57 - 80
Microbiological and clinical aspects of infection associated with Stenotrophomonas maltophilia; Denton M et al.; The gram-negative bacterium Stenotrophomonas maltophilia is increasingly recognized as an important cause of nosocomial infection . Infection occurs principally, but not exclusively, in debilitated and immunosuppressed individuals . Management of S . maltophilia-associated infection is problematic because many strains of the bacterium manifest resistance to multiple antibiotics . These difficulties are compounded by methodological problems in in vitro susceptibility testing for which there are, as yet, no formal guidelines . Despite its acknowledged importance as a nosocomial pathogen, little is known of the epidemiology of S . maltophilia, and although it is considered an environmental bacterium, its sources and reservoirs are often not readily apparent . Molecular typing systems may contribute to our knowledge of the epidemiology of S . maltophilia infection, thus allowing the development of strategies to interrupt the transmission of the bacterium in the hospital setting . Even less is known of pathogenic mechanisms and putative virulence factors involved in the natural history of S . maltophilia infection and this, coupled with difficulties in distinguishing colonization from true infection, has fostered the view that the bacterium is essentially nonpathogenic . This article aims to review the current taxonomic status of S . maltophilia, and it discusses the laboratory identification of the bacterium . The epidemiology of the organism is considered with particular reference to nosocomial outbreaks, several of which have been investigated by molecular typing techniques . Risk factors for acquisition of the bacterium are also reviewed, and the ever-expanding spectrum of clinical syndromes associated with S . maltophilia is surveyed . Antimicrobial resistance mechanisms, pitfalls in in vitro susceptibility testing, and therapy of S . maltophilia infections are also discussed.

Clin Microbiol Rev, 1998 Jan, 11(1), 1 - 26
Use of licensed vaccines for active immunization of the immunocompromised host; Pirofski LA et al.; The latter part of the 20th century has witnessed an unprecedented rise in the number of individuals with impaired immunity . This is primarily attributable to the increased development and use of antineoplastic therapy for malignancies, organ and bone marrow transplantation, and the AIDS epidemic . Individuals with impaired immunity are often at increased risk for infections, and they can experience more severe and complicated courses of infection . The lack of therapy for a variety of viruses and the rise in antimicrobial resistance of many pathogens have focused attention on vaccination to prevent infectious diseases . The efficacy of most licensed vaccines has been established in immunocompetent hosts . However, there is also considerable experience with most vaccines in those with impaired immunity . We reviewed the use of licensed live, inactivated, and polysaccharide vaccines in this group, and several themes emerged: (i) most vaccines are less immunogenic in those with impaired immunity than in normal individuals; (ii) live vaccines are generally contraindicated in this group; and (iii) the efficacy of many commonly used vaccines has not been established in people with impaired immunity . This review suggests that for most vaccines there are little or no efficacy data in those with impaired immunity but their use in this patient group is generally safe.

Lancet, 1998 Jan 24, 351(9098), 256 - 61
Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy; Carr A et al.; BACKGROUND: Enterocytozoon bieneusi and Cryptosporidium parvum cause chronic antimicrobial-resistant gastrointestinal infections in HIV-1-infected individuals . HIV-1 reverse transcriptase inhibitors delay the onset of opportunistic infections, but are not known to reverse established infections . HIV-1 protease inhibitors are more effective across a broader range of HIV-1-infected immune cells . Combination antiretroviral therapy that includes a protease inhibitor could improve immunity to E bieneusi and C parvum . METHODS: HIV-1 infected patients with chronic microsporidiosis (five), cryptosporidiosis (three), or dual infection (one), were treated with combination therapy that included at least one HIV-1 protease inhibitor . Outcome measures were symptoms, weight, use of antidiarrhoeal and antimicrobial drugs, T-lymphocyte subsets, HIV-1 viraemia, stool microscopy, and biopsy by endoscopy . FINDINGS: All patients had complete clinical responses, gained a median 15 kg in weight, and ceased all antidiarrhoeal and antimicrobial therapies . Biliary cryptosporidiosis responded in both affected patients . Neither pathogen was detected in follow-up stool microscopy (eight of eight patients) or in biopsy samples by endoscopy (five of five) . Intestinal architecture returned to normal in three patients . There was a dense CD8 lymphocyte and macrophage infiltrate and staining of intraepithelial E bieneusi with interferon-gamma before and after treatment, but little staining for CD4 or B lymphocytes, interleukin 10, or HIV-1 gp41 . Five patients remained symptom-free after a median 13 months follow-up . Four patients had recurrent diarrhoea at 7-13 months (one with positive stool microscopy), associated with declining CD4 counts . INTERPRETATION: Combination antiretroviral therapy that includes a protease inhibitor can restore immunity to E bieneusi or C parvum in HIV-1 infected individuals, and result in complete clinical, microbiological, and histological responses . The persistent CD8 cell and macrophage infiltrate, and the rapid time to relapse in patients with declining CD4 lymphocyte counts, suggest that neither infection was eradicated.

Am J Epidemiol, 1998 Jan 15, 147(2), 111 - 6
Characteristics of women with clinical intra-amniotic infection who deliver preterm compared with term; Krohn MA et al.; The authors sought to determine whether demographic factors, labor characteristics, and labor management for intra-amniotic infection (IAI) are different for IAI cases who deliver preterm compared with IAI cases who deliver at term . From 1990 through 1994, 610 women with intra-amniotic infection and 747 controls were enrolled from five hospitals in King County, Washington state . Intra-amniotic infection was diagnosed by fever 37.8 degrees C with two of the following signs: maternal or fetal tachycardia, uterine tenderness, elevated peripheral white blood cell count, and purulent amniotic fluid . Preterm IAI cases were significantly more likely than term IAI cases to have membrane rupture before contractions (odds ratio (OR) = 6.1) and prolonged membrane rupture (> 24 hours) (OR = 31.0) . Term cases were more likely to experience a prolonged second stage of labor . After accounting for differences in labor characteristics, preterm IAI was less likely to be managed with a cesarean delivery, prolonged internal monitoring, or induction of labor and more likely to be managed with antimicrobials and antipyretics . When compared with preterm births without IAI, preterm IAI cases were more likely to be managed with labor augmentation . The authors believe that labor characteristics of women with preterm IAI and the risk of neonatal sepsis deserve further study.

Complement Ther Nurs Midwifery, 1995 Aug, 1(4), 118 - 20
A review of the literature surrounding the research into aromatherapy; Cawthorn A; Whilst nurses in the UK are increasingly introducing aromatherapy into their practice, the research surrounding its use is still in its infancy . This position is in contrast to other parts of Europe such as France, where aromatherapy has been incorporated into areas of medical practice for some time, and is supported by increasing numbers of research papers . More recently, studies have been undertaken into the absorption of the essential oils, their therapeutic properties and the antimicrobial activity of certain oils . These studies will be reviewed, along with an evaluation of the studies undertaken in the UK into the use of aromatherapy with patients.

Clin Infect Dis, 1998 Jan, 26(1), 1 - 10; quiz 11-2
Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men; Craig WA; Investigations over the past 20 years have demonstrated that antibacterials can vary markedly in the time course of antimicrobial activity . These differences in pharmacodynamic activity have implications for optimal dosage regimens . The results of more recent studies suggest that the magnitude of the pharmacokinetic/pharmacodynamic parameters required for efficacy are relatively similar in animal infection models and in human infections . However, there is still much to learn . Additional studies are needed to further correlate pharmacokinetic/pharmacodynamic parameters for many antibacterials with therapeutic efficacy in a variety of animal infection models and in human infections . The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms, for setting susceptibility breakpoints, and for reducing the cost of drug development should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.

Rev Med Chir Soc Med Nat Iasi, 1996 Jul-Dec, 100(3-4), 232 - 5
{The synthesis of oximes and O-acetyl derivatives with biological activity}; Rusu G et al.; Data about synthesis of some oximes and their O-acetyl derivates are shown here . This item also emphasize the results of testing the antimicrobial, antifungal, antilevural and anti-inflammatory action of the synthesized oximes.

Rev Med Chir Soc Med Nat Iasi, 1995 Jul-Dec, 99(3-4), 195 - 201
{Pell-Nicol, a medicinal toothpaste}; Popovici I et al.; A medicinal toothpaste based on an atomized extract obtained out of sulfurous mud of Nicolina Iassy (a natural organic-mineral complex) has been formulated and physico-chemically characterized . The optimal formula has been chosen corresponding to following parameters: aspect, colour, taste, smell; weight/tube (65 g +/- 5%); Dentine Abrasion Value (D . A . V.) = 30; pH = 6.95-7.42; foaming capability of foam, in minutes = 0.40-0.60; residue on the sieve (g% = 0.09); heavy metals content; abrasive substances; g% = 32-37 at least; sodium chloride g% = 0.30 at least; firmness time = 30 sec . Also it have been effectuated rheological measurements and dynamic viscosity . The medicinal toothpaste Pell-Nicole presents a plastic behaviour with thixotropic character, which confers a good stability in time, an adequate firmness and comparable properties with others marketed products . The therapeutical effects have been tested, such as the antimicrobial and anti-inflammatory actions . The medicinal dentifrice toothpaste Pell-Nicole is recommended for gum affections, superficial chronic inflammatory forms, deep paradontopathies, as well as for a proper dental hygiene.

Kansenshogaku Zasshi, 1997 Nov, 71(11), 1144 - 54
{Report of questionnaire about enterohemorrhagic Escherichia coli cases caused in the area including Sakai City in 1996}; Yoh M et al.; Many outbreaks of EHEC O157 were occurred in Japan in 1996 . There was the biggest outbreak involving approximately 6000 victims in area of Sakai City . We conducted a questionnaire survey on the EHEC infection to the physicians who treated these patients and the microbiologists . For physicians we asked mainly clinical manifestation of patients they observed and treatment they did and their outcome (Answer A) . Microbiologists were also required to answer the opinion about treatment (Answer B) . Eighty-five of physicians replied about their 222 patients and 209 of microbiologists answered their opinions . In this report we summarized the data and obtained following results: 1) We observed higher frequency of HUS/TTA complication in female than male . 2) Higher HUS/TTP complication was accompanied with patients complained symptoms of fever, bloody diarrhea, and general fatigue . 3) The most patients (96%) were received antimicrobial agents, especially fosfomycin (84%), followed by new quinolon (17.8%) and Cefems (12.2%) . Later starting of treatment with antimicrobial agents than 7 days from onset of symptoms increased HUS/TTP complication . 4) Anti-diarrhoeal agents seems to be one of risk factors for HUS/TTP complications.

Biochemistry, 1998 Jan 27, 37(4), 983 - 90
Structural studies of Impatiens balsamina antimicrobial protein (Ib-AMP1); Patel SU et al.; Structural studies of Ib-AMP1, a small antimicrobial peptide derived from the seeds of Impatiens balsamina have been performed using circular dichroism (CD) and two-dimensional proton nuclear magnetic resonance (1H NMR) . This 20-residue peptide is highly basic with five arginine residues and contains four cysteines which form two intramolecular disulfide bonds . CD results reveal that the peptide may include a beta-turn but do not show evidence for either helical or beta-sheet structure over a range of temperature and pH . Structural information from NMR was obtained in the form of proton-proton internuclear distances inferred from NOEs and dihedral angle restraints from spin-spin coupling constants, which were used for distance geometry calculations . Owing to the difficulty in obtaining the correct disulfide connectivities by chemical methods, three separate calculations were performed; with no disulfides and with the two possible alternate disulfide connectivities . Results from distance geometry calculations reveal that although the peptide is small, the cysteines constrain part of it to adopt a well-defined main chain conformation . From residue 6 to 20, the backbone is well defined, whilst the N-terminal region, residues 1-5, has very few constraints and appears to be very flexible . In the defined core region, there are three beta-turns at residues 9-12, 10-13, and 12-15 . The side chains show no strong interactions in the NMR spectra and are therefore thought to adopt multiple conformations . Superposition of the structures generated shows that the peptide has two hydrophilic patches which are at opposite ends of the molecule separated by a large hydrophobic patch . Little is known about the mode of action of this protein, but it is thought to interact with a membrane-bound receptor, and possible sites of interaction are discussed . The structures determined are compared with those of the alpha-conotoxins, which are also highly basic proteins with similar disulfide connectivities.

Arzneimittelforschung, 1997 Oct, 47(10), 1165 - 71
{30 years development of antibiotics}; Wiedemann B; Many new antibiotics with improved pharmacodynamic and pharmacokinetic properties have been developed in the last 30 years . This development, however, went down in the last five years . With modern techniques of sequencing of the complete bacterial genum in order to find new targest, with combinatory chemistry and with the high throughput screening about one new drug per year can be developed in the future . The activity of antibiotics is diminished by the increasing number of resistant strains and by the increase of infections with naturally resistant microorganisms . The rational use of antibiotics can slow down this trend and perhaps reverse it . To reach this aim it is necessary to increase research activities in the field of pharmacodynamics in order to allow a more rational dosing . Better technology documentation and statistics in microbiological diagnostics could improve calculated chemotherapy . Furthermore we need more information about the epidemiology of resistant bacteria, at least the knowledge about receptors, mechanism of action and mechanism of resistance should be known to circumvent these obstacles in antimicrobial chemotherapy.

Compend Contin Educ Dent, 1997 Apr, 18(4), 325 - 6, 328, 330 passim; quiz 336
Topical tetracycline: potential for allergic reaction or bacterial resistance; Encarnacion M et al.; The high incidence of allergic reactions to some common dental antibiotics, primarily topical penicillins, has led to general concerns about all topical antibiotics . The development of resistant bacterial strains and efforts to reserve key antibiotics for life-threatening infections have also limited topical use of antibiotics . Delivery technologies providing for site-specific drug delivery have renewed interest in the use of topical antimicrobials to treat adult periodontitis . Topical tetracycline has an extremely low sensitizing potential and is not one of the antibiotics reserved by the medical community for use in life-threatening situations . Despite tetracycline's widespread dermatologic use and increasing use in adjunctive treatment of adult periodontitis, the incidence of allergic response to topical tetracycline is very low . Also, it is unlikely to cause resistance when used locally for short durations--particularly at the high per-site concentrations achieved with tetracycline periodontal fiber . Studies with tetracycline fiber showed no significant change in the tetracycline susceptibility of gram-negative periodontal microorganisms.

Clin Infect Dis, 1997 Dec, 25(6), 1462 - 4
Anaerobic meningitis due to Peptostreptococcus species: case report and review; Korman TM et al.; We describe a patient with postsurgical anaerobic meningitis due to Peptostreptococcus magnus . In cases of meningitis associated with Peptostreptococcus species reported in the literature, the most common predisposing factors are meningorectal fistulae and head-and-neck surgery . Most patients respond well to appropriate antimicrobial therapy . Surgical intervention may be required in some instances.

Clin Infect Dis, 1997 Dec, 25(6), 1430 - 40
Interactions between tacrolimus and antimicrobial agents; Paterson DL et al.; Tacrolimus is being increasingly used as an immunosuppressive agent in transplant recipients . The drug is metabolized by the cytochrome P-450 3A system, thus antimicrobials that inhibit or induce these enzymes can alter levels of tacrolimus in the bloodstream . Tacrolimus is potentially nephrotoxic and neurotoxic; the likelihood of toxicity rises as blood levels of the drug increase . Increased tacrolimus levels and subsequent toxicity have been produced by a number of antimicrobial agents that inhibit the cytochrome P-450 3A system . Conversely, drugs with the potential to induce the cytochrome P-450 3A system can reduce the levels of tacrolimus in the blood, leading to increased risk of acute rejection in transplant recipients . Antimicrobial agents that can have adverse effects on renal function may add to the nephrotoxicity of tacrolimus . The potential for drug interactions should be reviewed before antimicrobial agents are prescribed to patients treated with tacrolimus.

Clin Infect Dis, 1997 Dec, 25(6), 1310 - 7
Prevention and management of infection after total joint replacement; Gillespie WJ; Prophylactic antimicrobial regimens providing adequate drug levels in tissue during surgery and for periods of 24 hours to 14 days are of proven effectiveness in reducing infection rates after joint arthroplasty . Although most surgeons employ short regimens of < 24 hours' duration, their efficacy has not been clearly established for joint replacement in placebo-controlled trials . Careful preparation of the patient before surgery and attention to operating room asepsis are also important . In early postoperative infections, surgical debridement and antibiotic treatment may allow conservation of the prosthetic components . In established infection in which the components have become loose, radical surgical debridement must include removal of all prosthetic material as well as involved bone and soft tissue; reconstruction by exchange arthroplasty has an acceptable success rate . For infections caused by organisms of low virulence, exchange arthroplasty has been successful as a one-stage procedure, but no comparative trial with two-stage exchange has yet been reported.

Proc Natl Acad Sci U S A, 1997 Dec 23, 94(26), 14614 - 9
Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms; Lemaitre B et al.; Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides . Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms . We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms . More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities . This response is mediated through the selective activation of the Toll pathway.

Pharmacol Res, 1997 Sep, 36(3), 193 - 7
Antifungal, antibacterial, antiviral and cytotoxic activity of novel thio- and seleno-azoles; Deidda D et al.; A series of pentaatomic heterocyclic compounds containing sulphur or selenium in position 2, were tested for cytotoxicity, antiviral and antimicrobial activities . Generally, selenium-containing compounds were more toxic than the corresponding sulphur-containing ones (30-75 times more toxic) and, furthermore, the biological activity against some microorganisms was also enhanced . In particular, some selenium-containing derivatives exerted an inhibitory activity on plant pathogenic fungi at doses markedly lower than the toxic ones, showing an interesting selectivity of action . In this case the tested compounds appeared more active than ketoconazole, the control used, with an almost comparable degree of cytotoxicity .

Health Policy, 1998 Mar, 43(3), 219 - 32
Controlling antimicrobial resistance: a proposed transferable permit market; Smith RD et al.; Resistance to antimicrobials results in those antimicrobials becoming ineffective in treating common bacterial infections . To prevent the spread of such resistance the use of antimicrobials requires control . The authors have previously argued that use of regulation or charges to control resistance would not be efficient . Regulation will not account for different marginal costs of reducing antimicrobial prescription amongst GPs, and charges, although based on sound economic concepts, are based on an unrealistic amount of required information . It was therefore argued that a system of tradable permits, by combining the targets of regulation and the market flexibility of charges, would achieve control more efficiently than simple regulation or charges . In this paper the authors progress this proposed policy by considering various important issues which arise when designing such a tradable permit system for antimicrobials . The paper does not provide an exhaustive plan enabling a blueprint for such a market to be designed, but a proposal which may be used as platform for further specific development of such an initiative to deal with resistance.

Zentralbl Veterinarmed B, 1997 Nov, 44(9), 523 - 8
The efficacy of enrofloxacin in-feed medication by applying different programmes for the control of post weaning oedema disease in weaned piglets; Kyriakis SC et al.; Oedema disease (OD) usually occurs after weaning and is due to infection with (ETEEC) enterotoxaemic Escherichia (E.) coli . This study further examines the efficacy of three different in-feed usage programmes of enrofloxacin (ENR/Baytril I.E.R . 2.5%), on the control of post weaning OD in piglets . The recommended in-feed dosage of ENR for this clinical indication, i.e . 50 p.p.m., was used . Five groups with a total of 240 weaned piglets for 28 days period were used in this trial . One group (negative control) was offered feed free of antimicrobials, one group was offered feed as that of the negative control group except that the feed consumption was restricted for the first 12 days post weaning, and three groups were offered feed ad libitum medicated with 50 p.p.m . of ENR starting 7 days after weaning for 5, 7 and 10 days, respectively, and were compared with regard to their performance . Mortality was lower compared to the negative control group in all ENR treatments (P < 0.05) . The evaluation of the growth performance data, as well as feed conversion ratio, indicated that the three treated groups performed remarkably better than the control group (P < 0.05) . It was concluded that a strategic medication initiated 7 days post weaning with 50 p.p.m . of ENR and usually for a 10 day period is useful in controlling and/or preventing post weaning OD due to ETEEC.

Zentralbl Veterinarmed B, 1997 Nov, 44(9), 513 - 21
The efficacy of enrofloxacin in-feed medication, by applying different programmes for the control of post weaning diarrhoea syndrome of piglets; Kyriakis SC et al.; Post weaning diarrhoea syndrome (PWDS) in piglets is caused mainly by enterotoxigenic Escherichia (E.) coli (ETEC) strains . Six different in-feed usage programmes of enrofloxacin (ENR/Baytril; I.E.R . 2.5%) were tested for their efficacy on the control of post weaning colibacillosis in piglets, using seven groups with totally 336 weaned piglets for a 28 day period . One group (negative control) was offered feed free of antimicrobials, three groups were offered feed medicated with 50 ppm of ENR starting on weaning day for 5, 7 and 10 days respectively, three groups were offered feed medicated with 50 ppm of ENR starting 7 days post weaning for 5, 7 and 10 days respectively, and were compared with regard to the appearance of clinical signs, mortality, weight gain and feed conversion . The results showed that all ENR treatments reduced the incidence and severity of diarrhoea . Mortality was similar in all ENR treatments, but in the groups where the ENR was added for 10 days immediately after weaning and/or 7 days post weaning for 7 and 10 days respectively was lower compared to the negative control group (P < 0.05) . The evaluation of the weight gain data, as well as feed conversion ratio indicated that the six treated groups performed remarkably better than the control group (P < 0.05) . No ETEC were detected on days 21 and 28 in all ENR groups contrary to the untreated control . It was concluded that a strategic medication initiated 7 days post weaning with 50 ppm of ENR and only for 7 and 10 days period of time is a useful tool in controlling PWDS due to ETEC.

World J Surg, 1998 Feb, 22(2), 187 - 96
Roles of nitric oxide in surgical infection and sepsis; Johnson ML et al.; Recent advances in nitric oxide (NO) research have begun to elucidate the roles of NO in sepsis and infection . Although adequate levels of NO production are necessary to preserve perfusion and carry out cytoprotective functions in sepsis, overproduction appears to contribute to hemodynamic instability and tissue damage . These observations have led to the development of strategies to inhibit NO synthesis or scavenge excess NO in patients with septic shock . Local expression of the inducible NO synthase also has antimicrobial functions . The combination of NO with superoxide forms peroxynitrite which participates in bacterial killing in the peritoneal cavity . The capacity of red blood cells and hemoglobin to remove NO most likely accounts for the adjuvant effect of blood in peritonitis . This review will summarize the pathobiology of NO in surgical sepsis and infection.

Lett Appl Microbiol, 1997 Dec, 25(6), 437 - 41
SYTO16 labelling and flow cytometry of Mycobacterium avium; Ibrahim P et al.; Mycobacterium avium cells were harvested from agar at different stages of their growth cycle, exposed to the minimum inhibitory concentration of isoniazid (INH) for 24 h and labelled with the fluorescent nucleic acid stain SYTO16 . INH exposure led to a > 10-fold increase in the intensity of labelling in the majority of cells, and revealed discrete fluorescence peaks that were consistent with development of filamentous multinucleate cells during the growth cycle . Similar enhancement of labelling was observed in unfixed INH-treated cells viewed by fluorescence microscopy . INH appears to increase the permeability of Myco . avium cells to SYTO16 . A combination of growth cycle-defined inocula, labelling with the new generation of fluorescent dyes and flow cytometry provides new opportunities to study the interrelationships between growth cycle events and antimicrobial susceptibility of mycobacteria.

Folia Microbiol (Praha), 1997, 42(4), 324 - 6
Antimicrobial effects of the macrocyclic Cu(II)-tetraanhydroaminobenzaldehyde complex; Jantova S et al.; The Cu(II)-tetraaza macrocyclic complex exhibited antimicrobial effects on bacteria, yeasts and filamentous fungi . The highest antibacterial activity was found with B . subtilis and S . aureus, the respective IC50 values being 18 and 80 micrograms/L and the MIC values 50 and 1000 micrograms/L . A concentration of 1 mg/L exerted a bacteriocide effect on S . aureus . The MIC value for B . subtilis was 250 times lower and for P . aeruginosa 10 times lower than the corresponding values for ampicillin . The Cu-complex was inactive against all tested yeasts . The strongest antifungal effect was manifested for R . nigricans, with an IC50 value under 0.1 mg/L, whereas in A . alternata the IC50 was 13.5 mg/L.

Antimicrob Agents Chemother, 1998 Jan, 42(1), 83 - 7
Comparison of the efficacies of three fluoroquinolone antimicrobial agents, given as continuous or pulsed-water medication, against Escherichia coli infection in chickens; Charleston B et al.; This study compared the efficacy of continuous or pulsed-water medication with enrofloxacin, danofloxacin, and sarafloxacin in eight groups of 90 chicks each by using an infectious bronchitis virus-Escherichia coli model of colisepticemia . The model produced lesions of typical those occurring in birds with severe colisepticemia; for the infected, nonmedicated birds the mortality was 43.5% and the morbidity was 89%, 17.8% of birds had severe lesions, and the birds had a mean air sac lesion score of 2.58 . This experiment showed that continuous dosing and pulsed dosing are clinically equivalent . However, for all fluoroquinolones studied, there was a trend for the continuously mediated birds to have lower mortality and less severe disease than birds receiving pulsed doses . Compared with infected, nonmedicated controls, only birds continuously medicated with enrofloxacin had a significantly lower morbidity (32%), and only birds medicated with enrofloxacin and danofloxacin (continuous and pulsed treatments) had significantly lower mortality (6.7 and 11.0% and 16.8 and 19.2% for continuous and pulsed treatments with enrofloxacin and danofloxacin, respectively) . A significantly lower proportion of birds only in the groups medicated with enrofloxacin had severe lesions (for birds receiving continuous and pulsed treatments, 2.2 and 6.7%, respectively) . Birds medicated with any of the three fluoroquinolones (continuous and pulsed treatments) except pulsed-water treatment with sarafloxacin had significantly reduced mean air sac lesion scores compared with the scores for nonmedicated birds (air sac lesion scores, 0.60 and 0.83, 1.38 and 1.63, and 1.80 and 2.05 for birds receiving continuous and pulsed treatments with enrofloxacin, danofloxacin, and sarafloxacin, respectively) . The performance of the birds that survived the challenge or that recovered after receiving medication was not compromised compared to the performance of noninfected birds . Enrofloxacin was more efficacious than either danofloxacin or sarafloxacin for the treatment of colisepticemia in chickens by medication in drinking water . Similarly, danofloxacin appeared to be more effective than sarafloxacin in treating colisepticemia.

Curr Opin Rheumatol, 1998 Jan, 10(1), 3 - 11
New developments in pathogenesis of systemic vasculitis; Nowack R et al.; Aspects of pathogenesis of primary systemic vasculitis are highlighted in this review . The cause of these entities is still obscure, although new information on the possible role of infections has emerged . Success of antimicrobial treatment to ameliorate systemic vasculitis, for which proof was recently provided, adds to the new information . Apart from new data that point to a precipitating role for environmental toxins the background for development of these diseases is most likely genetic predisposition . Reports on hereditary alpha 1-antitrypsin deficiency, the link between systemic vasculitis and human leukocyte antigen molecules, and an animal model of spontaneous granulomatous arteritis in mice with a hereditary deficit in Fas-mediated apoptosis, are some of the new data that strongly favor genetic predisposition . Progress has been made in the process of identification of the agonists and antagonists in the front line of vasculitic inflammation . The interaction of blood cells (e.g., neutrophils and monocytes) with vascular endothelium has become more evident as have the signals for the release of harmful proteolytic enzymes . Antineutrophil cytoplasmic antibodies, which are important markers of disease, may be actively involved in these processes.

Crit Care Clin, 1998 Jan, 14(1), 105 - 18
Severe community-acquired pneumonia; Cunha BA; Community-acquired pneumonia (CAP) is likely to be severe in the very elderly, and clinically significant in those with hepatic/ renal insufficiency, cardiopulmonary disease, or, impaired host defenses . Pathogens in mild, moderately severe, and severe CAP are the same . These pathogens determine prognosis, complications, and duration of therapy . Empiric antimicrobial therapy should be based on likely pathogens, not severity of illness which affects the potency but not spectrum of antibiotic selected.

Crit Care Clin, 1998 Jan, 14(1), 71 - 90
Infection versus colonization in the critical care unit; Bergen GA et al.; Serious infections in the critical care unit are commonplace . However, distinguishing true infection from mere colonization is a difficult and often uncertain process that has been shown to result in both over- and under-treatment of patients . Antimicrobial agents used in the CCU setting are expensive and not without toxicities . This article discusses methods to differentiate colonization from infection.

J Am Vet Med Assoc, 1998 Jan 15, 212(2), 248 - 53
Pericarditis in horses: 18 cases (1986-1995); Worth LT et al.; OBJECTIVE: To determine clinical signs of pericarditis in horses and to determine whether there were any relationships among clinical signs, echocardiographic findings, treatment, and outcome . DESIGN: Retrospective study . ANIMALS: 18 horses . RESULTS: Physical examination was performed on 16 horses . Cardiovascular abnormalities included tachycardia (n = 16), pericardial friction rub (10), venous distention (7), murmur (7), muffled heart sounds (6), weak arterial pulse (6), jugular pulse (6), and edema (5) . Twelve horses also had respiratory abnormalities; the most common was dull lung sounds, ventrally, suggestive of pleural effusion (10) . Echocardiography was the most important tool for diagnosis of pericarditis . Detection of clinical signs of right-sided heart failure was significantly associated with severe accumulation of pericardial effusion and with detection of cardiac compromise . Severe accumulation of pericardial effusion was also significantly associated with echocardiographic detection of cardiac compromise . Pericarditis was idiopathic in 6 horses, and bacterial in 5 . Five horses had nonseptic pericarditis associated with bacterial respiratory disease, and 2 had nonseptic pericarditis associated with viral respiratory disease . Fourteen of the 18 horses were treated specifically for pericarditis; 10 received antimicrobials and 6 with suspected immune-mediated pericarditis received corticosteroids . Pericardial drainage and lavage were performed on 6 horses in which pericardial effusion or fibrin accumulation was compromising cardiac function . Pericarditis resolved in all 14 horses that were treated, and all 14 returned to their prior intended use . CLINICAL IMPLICATIONS: With early detection of disease and aggressive treatment, the prognosis for horses with pericarditis is good.

Am J Gastroenterol, 1998 Jan, 93(1), 35 - 8
Randomized clinical trial comparing two one-week triple-therapy regimens for the eradication of Helicobacter pylori infection and duodenal ulcer healing; Forne M et al.; OBJECTIVE: One-week triple therapy has been shown to be effective in Helicobacter pylori eradication and duodenal ulcer healing . However, the optimal therapeutic combination has not yet been identified . Bismuth-containing regimens have the advantage of requiring only one antibiotic . It has been suggested that high doses of omeprazole improve the bactericidal efficacy of antimicrobial regimens against H . pylori . We evaluated the efficacy of two 1-wk triple-therapy regimens for H . pylori eradication and duodenal ulcer healing . METHODS: On an intention-to-treat basis, 182 patients with H . pylori-associated duodenal ulcer were randomized . Group OCB patients (n = 91) were given omeprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d., and colloidal bismuth subcitrate 120 mg q.i.d . for 7 days . Group OCA patients (n = 91) were treated with omeprazole and clarithromycin at the same doses plus amoxicillin 1 g b.i.d., also for 7 days . Endoscopies were performed at entry and at 4 wk after the end of treatment . The presence of H . pylori was assessed by urease test, histology, Gram stain, and culture . No patient received follow-up treatment . RESULTS: H . pylori eradication rates achieved in the OCB and OCA groups were similar whether by intention-to-treat (82.4% vs 88.9% ;p = 0.21) or per protocol analysis (83.3% vs 89.9%; p = 0.19) . Duodenal ulcer healing rates also were the same for OCB and OCA in intention-to treat (91.2% vs 91.1%) and per protocol analysis (92.2% vs 92.1%), respectively (p = 0.98) . CONCLUSIONS: High rates of H . pylori eradication and duodenal ulcer healing were obtained with both short-treatment regimens, which were safe and well-tolerated . Colloidal bismuth subcitrate seems to be a good alternative to amoxicillin in the triple-therapy combination with omeprazole and clarithromycin . The omeprazole dose does not seem to play a major role in H . pylori eradication in these therapeutic combinations.

Mol Cell Biol, 1998 Feb, 18(2), 807 - 14
Isolation of developmentally regulated genes from Toxoplasma gondii by a gene trap with the positive and negative selectable marker hypoxanthine-xanthine-guanine phosphoribosyltransferase; Knoll LJ et al.; Within its intermediate host, Toxoplasma gondii switches between two forms: a rapidly replicating tachyzoite and an encysted bradyzoite . Bradyzoites persist within the host throughout its life, hidden from antimicrobial agents and the immune system . The signals that mediate switching are poorly understood . A gene trap was employed to isolate genes whose expression is up-regulated early in the switching of bradyzoites via the negative and positive selectable marker hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) . T . gondii was transfected with promoterless HXGPRT and negatively selected with 6-thioxanthine to inhibit the growth of tachyzoites expressing HXGPRT . The surviving tachyzoites were then induced for in vitro bradyzoite formation and treated with mycophenolic acid and xanthine to positively select for parasites in which the construct had integrated downstream of a bradyzoite-specific gene . Strains were checked for their ability to differentiate by using Dolichos biflorus agglutinin (a bradyzoite-specific lectin) and a monoclonal antibody against P36 (a bradyzoite-specific surface antigen) . After differentiation, all gene-trapped clones had Dolichos immunofluorescence and all but one expressed P36 . The sequences flanking the insertion site of this P36-negative strain were homologous to the Toxoplasma family of surface antigens, strongly suggesting that P36 is encoded by the disruptive gene . Genetic mapping and complementation of the P36-negative strain further indicated that the disrupted gene is P36 . Reverse transcriptase PCR and S1 nuclease digestion were used to compare mRNA levels during the tachyzoite and bradyzoite stages . The presumptive P36 gene does not appear to regulate its mRNA levels between the two stages, indicating a posttranscriptional mechanism of regulation for early bradyzoite-specific genes.

J Clin Pharm Ther, 1997 Jun, 22(3), 227 - 35
Antibiotics prescription for indigent patients in primary care; Tzimis L et al.; OBJECTIVE: A drug use evaluation focusing on prescribed antibiotics among Greek indigent and Social Security patients . METHOD: Four hundred and forty-six indigent patients insured by Social Care and 332 patients insured under Social Security Funds were interviewed and their prescription records reviewed . RESULTS: Although 88.5% of indigent patients stated that they had received instructions on antibiotic use and had understood these instructions, only 45.9% could correctly repeat these instructions . Only 9.9% read the enclosed leaflets and 59.4% reported asking the pharmacist for advice, 54.1% of these patients were unaware of the dosage of their medication, and the length of treatment was only written in 13% of cases . The most common diseases among indigent patients were respiratory infection (11.7%) and dental problems (10.1%) . The latter ranked 11th among the insured patients (3.7%) . Tuberculosis (3.3%) was still one of the most common diseases among the indigent patients . Overall, 30.9% of the prescribed daily defined dose (DDD) of medication for the indigent patients were for cardiovascular drugs (16.9% of the cost), 19.5% were for nervous system drugs (8.9% of the cost), 13.5% for gastrointestinal tract drugs (14.1% of the cost) and only 4.3% were antibiotics (but 16.9% of the cost) . The most frequently prescribed antimicrobials were penicillins (45.6%), cephalosporins (19.7%), macrolides (12.6%) and quinolones (9.6%) . Antituberculous agents made up 13.7% of the antibiotic prescriptions . The most widely prescribed antibiotics were amoxycillin + clavulanate (19.3%), amoxycillin (7.9%), cefaclor (5.6%), clarythromycin (5.1%) and rifampicin + isoniazid (6.3%) . CONCLUSION: The present study emphasizes the need for more information on drug use among indigent patients and their information needs.

Ugeskr Laeger, 1997 Dec 29, 160(1), 50 - 2
{Aminoglycoside treatment II: Dosage regimes at the departments of internal medicine in Denmark}; Lund ES et al.; The aim of this study was to get a general view of the habitual practice of the usage of aminoglycosides in Danish medical departments, regarding choice of drug, dosage regimen and monitoring of drug-related toxicity, as this antimicrobial agent is commonly used in Danish hospitals against severe infections in spite of the potential for nephro- and ototoxicity . The survey, taking place in 1991 and in 1994, showed that gentamicin and netfilmicin were preferred as first choice with an equal frequency in university and county hospital department, whereas in departments in small hospitals gentamicin was preferred twice as often . From 1991 to 1994 the dosage regimen most commonly used had altered from thrice-a-day to once-a-day . Monitoring of serum levels of the drug was performed on all treated patients in fifty-two of the seventy-nine departments questioned . Most of the departments also monitored the kidney function.

Acta Pol Pharm, 1996 Jul-Aug, 53(4), 277 - 81
Synthesis and antibacterial activities of some new arenesulfonamides and urea derivatives; Dogan N et al.; Reactions of 3-substituted-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones {I} with some arenesulfonyl chlorides and aryl isocyanates were studied and the corresponding N-(3-substituted-4,5,-dihydro-1H-1,2,4-triazol-5-one-4-yl) arenesulfonamides {II-VI} and N-aryl-N-(3-substituted-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl) ureas {V, VI} were obtained . The structural assignments of new 19 compounds are based on spectral data and elemental analysis . Furthermore, compounds II-VI were tested for their in vitro antimicrobial activities.

Eur J Med Res, 1995 Oct 16, 1(1), 9 - 15
Decreased function of monocytes and granulocytes during HIV-1 infection correlates with CD4 cell counts; Dobmeyer TS et al.; Monocytes and neutrophils are involved in the primary immune response against opportunistic infections that occur during the progression of human immunodeficiency virus (HIV) infection towards development of acquired immune deficiency syndrome (AIDS) . Phagocytic cells operate through the generation of reactive oxygen species which may be toxic for fungi, bacteria and viruses . In the present study we evaluated the function of monocytes and granulocytes in whole blood samples of 16 healthy controls, 12 HIV infected subjects who had not undergone significant infections and of 17 individuals with AIDS . Using flow cytometric methods we were able to determine phagocytosis and respiratory burst under conditions that reflect the normal environment of these cells . Compared with results in samples from controls, granulocytes and monocytes from asymptomatic HIV infected patients exhibited a significantly increased capacity to phagocytose bacteria . The production of reactive oxygen intermediates was in the normal range . In comparison to asymptomatic HIV infected individuals, patients with AIDS showed a significant reduction of phagocytosis and respiratory burst which correlated with the number of CD4+ cells . In comparison to controls, patients infected with HIV, whether they were symptomatic or not, revealed a significantly diminished number of oxygen radical producing cells compared with the number of phagocytic cells . These results indicate that monocytes and granulocytes show reduced antimicrobial activity even in early stages of HIV infection . This defect is only partly due to the HIV infection itself as neutrophils are not target cells for HIV.

Int Surg, 1997 Jul-Sep, 82(3), 316 - 8
Penetrating thoraco-abdominal war injuries; Ilic N et al.; BACKGROUND: From April 1991 till December 1995, Split University Hospital played a major role as a third echelon war hospital during the war in Croatia and Bosnia and Herzegovina . Among 2856 treated battle casualties in general, 70 patients with penetrating thoraco-abdominal war injuries were treated at the Department of Surgery . Explosive wounds were present in 38 (54%), gunshot wounds in 32 (45%) and puncture wounds in four (5.70%) patients . METHODS: The medical data from the evacuation unit, transportation, emergency department, surgical management and follow-up were obtained and analyzed . The principle of treatment of such patients is described, with particular reference to thoracophrenolaparotomy as the most efficient diagnostic-therapeutic surgical approach . RESULTS: There were considerably more explosive wounds than gunshot and puncture wounds (ratio 38/32/4) . Resource utilization analysis showed a great amount of blood products (average 1.250 ml per patient), rehydrant solutions (average 3.750 ml per patient) and seven days antimicrobial chemoprophylaxis (penicillin, gentamycin, metronidazole) used . Mean time elapsed between injury and definitive surgical repair was seven hours (range, 1 to 48 hours) . Recovery on discharge was recorded in 61 (80%) and lethal outcome in nine (13%) patients . CONCLUSIONS: The treatment of respiratory insufficiency and hemorrhagic shock, and prevention of infection are the basis of the management of these injuries . Treatment success depends on emergency first-aid, quick transportation, early diagnosis, resuscitation, surgical therapy and intensive care.

Chemotherapy, 1998 Jan-Feb, 44(1), 31 - 5
Antimicrobial susceptibility testing of dermatophytes--comparison of the agar macrodilution and broth microdilution tests; Niewerth M et al.; Fifty dermatophyte strains, recently obtained from clinical material, belonging to 4 different species were examined for their susceptibility to 5 systemic or topical antimycotic agents using both an agar macrodilution and a broth microdilution test . Antimycotics compared were griseofulvin, itraconazole, sertaconazole, terbinafine and ciclopiroxolamine . A comparison of the minimum inhibitory concentrations (MIC) clearly showed differences between the two test methods applied . For all 5 antimycotics, MIC data were three- to seventy-fold lower in the microdilution test system . These differences, depending on the test method, have to be taken into account when comparing MIC data in the literature or when relating the in vitro data to the tissue concentrations determined in vivo.

Chemotherapy, 1998 Jan-Feb, 44(1), 17 - 20
Helicobacter pylori: in vitro induction of resistance to azithromycin; Kalenic S et al.; Helicobacter pylori resistance to macrolides is possibly an important factor for the failure of macrolide therapy for H . pylori infection . The aim of this study was to assess the propensity of H . pylori to develop in vitro resistance to azithromycin . In 73 clinical isolates taken from patients before starting antimicrobial therapy of H . pylori infection, MIC was determined using an agar dilution method (Muller-Hinton agar with 7.5% unlysed horse blood, pH = 7.2, at 35 degrees C, during 72 h in a humid microaerobic atmosphere) . Each strain was first cultivated at half minimal inhibitory concentration (MIC) then in doubling concentrations until growth arrest . All experiments for induction of resistance were performed on the same media, incubation temperature, atmosphere and time of MIC determination . MIC interpretative standards for sensitivity, intermediate sensitivity and resistance of H . pylori to azithromycin were < or = 2, 4 and > or = 8 mg/l, respectively . Of 73 strains, 5 died during the experiments, and in the remaining 68 strains, serial passage with increasing azithromycin concentrations resulted in the development of resistance in 19 (26.9%) strains . Two strains had an MIC of 16 mg/l azithromycin . Thirty-three (48.5%) strains kept the same MIC or doubled their MIC, 16 (23.5%) strains had 4- to 16-fold MIC but still remained sensitive, 2 resistant strains had 128-fold MICs and 17 resistant strains had increased their MICs more than 128 times . Seventeen highly resistant strains (MIC > 128 mg/l) were kept frozen at -70 degrees C for 3 months in a brain-heart infusion broth with 15% glycerol . MIC was assessed again to determine the stability of resistance . Eleven strains kept MICs > 128 mg/l, 2 became sensitive and 1 intermediate, but reverted easily, after only 2 passages, to an MIC of > 128 mg/l azithromycin . Although macrolides are very active against H . pylori, the propensity to develop resistance in a high proportion of strains has a clear impact on the choice of the right combinations of macrolides with other agents as well as the dosage of the macrolide antibiotics.

Indian J Pathol Microbiol, 1997 Oct, 40(4), 569 - 81
Emerging and re-emerging infections; Ranga S et al.; PIP: Emerging infectious diseases are diseases of infectious origin whose incidence in humans has increased within the past decades or threatens to increase in the near future . The reappearance of a previously known infection after a period of disappearance or decline in incidence is known as re-emergence . Many factors are known to contribute to the emergence or re-emergence of a disease . For example, research indicates that newly emergent infections may result from changes in or the evolution of existing organisms, the spread of known diseases to new geographic areas or human populations, or the appearance of previously unrecognized infections in persons living or working in areas undergoing ecologic changes which increases individual exposure to insects, animals, and environmental sources which may harbor new or unusual infectious agents . An infectious disease may re-emerge due to a range of reasons, including the development of antimicrobial resistance and/or insecticide resistance among vectors, and the collapse of public health systems . Pathology and emerging infections, examples of emerging and re-emerging infections, the contributions of pathology to emerging infections, autopsy and emerging infections, global microbial threats, emerging and re-emerging infections in India, tuberculosis, nosocomial infections, the current status of infectious disease pathology, and combatting infectious disease threats are discussed .

Microb Drug Resist, 1997 Winter, 3(4), 289 - 95
A bacterial model system for understanding multi-drug resistance; Saier MH Jr et al.; Mankind stands at the crossroads, recognizing the need for a radical change in bacterial disease management . The development of several antimicrobial agents in the 1940s and 1950s allowed man to gain the upper hand in controlling these diseases . However, the horizon is now clouded by the activation in bacteria of cryptic multi-drug resistance (MDR) genes and the spread of plasmid- and integron-born MDR genes through bacterial populations . Unless remedial measures are taken, nearly all currently available antimicrobial agents are likely to soon lose their efficacies . We briefly review the bacterial MDR phenomenon and focus on a recently emerging family of small multi-drug resistance (SMR) pumps which may provide an ideal model system for understanding the MDR phenomenon in general.

Am J Vet Res, 1998 Jan, 59(1), 44 - 7
Antimicrobial susceptibility of Fusobacterium necrophorum isolated from bovine hepatic abscesses; Lechtenberg KF et al.; OBJECTIVE: To determine the resistance and susceptibility to antimicrobial compounds of Fusobacterium necrophorum isolates from bovine hepatic abscesses . PROCEDURE: 37 isolates of F necrophorum (21 subsp necrophorum and 16 subsp funduliforme) isolated from bovine hepatic abscesses were obtained from cultures grown and maintained in anaerobic brain heart infusion broth . A broth dilution method was used as an initial screening to determine general susceptibility to 31 antimicrobial compounds . The minimal inhibitory concentrations (MIC) of 19 of the antimicrobial compounds that inhibited growth in the initial test were determined by use of the broth microdilution method . RESULTS: Fusobacterium necrophorum isolates were generally susceptible to penicillins, tetracyclines (chlortetracycline and oxytetracycline), lincosamides (clindamycin and lincomycin), and macrolides (tylosin and erythromycin), and were resistant to aminoglycosides (kanamycin, neomycin, gentamicin, and streptomycin), ionophores (except narasin), and peptides (avoparcin, polymyxin, and thiopeptin) . The 5 antimicrobials (bacitracin, chlortetracycline, oxytetracycline, tylosin, and virginiamycin) that have FDA approval for prevention of liver abscesses in feedlot cattle were inhibitory to F necrophorum . Differences in antimicrobial susceptibility patterns were observed between the 2 subspecies only for clindamycin and lincomycin . The MIC of F necrophorum isolates from antibiotic-fed cattle were similar to those for isolates from nonantibiotic-fed cattle . CONCLUSIONS: The MIC of FDA-approved antibiotics were not reflective of the efficacy of antibiotics in preventing liver abscesses in feedlot cattle . Also, continuous feeding of tylosin did not appear to select resistant F necrophorum.

J Biol Chem, 1998 Jan 23, 273(4), 2059 - 66
Lycotoxins, antimicrobial peptides from venom of the wolf spider Lycosa carolinensis; Yan L et al.; Two peptide toxins with antimicrobial activity, lycotoxins I and II, were identified from venom of the wolf spider Lycosa carolinensis (Araneae: Lycosidae) by virtue of their abilities to reduce ion and voltage gradients across membranes . Both peptides were purified to homogeneity by reversed-phase liquid chromatography and determined to have the following primary structures by Edman microsequencing: IWLTALKFLGKHAAKHLAKQQLSKL-NH2 for lycotoxin I and KIKWFKTMKSIAKFIAKEQMKKHLGGE-OH for lycotoxin II . The predicted secondary structures of the lycotoxins display amphipathic alpha-helix character typical of antimicrobial pore-forming peptides . Antimicrobial assays showed that both lycotoxins potently inhibit the growth of bacteria (Escherichia coli) and yeast (Candida glabrata) at micromolar concentrations . To verify its hypothesized pore-forming activity, lycotoxin I was synthesized and shown to promote efflux of Ca2+ from synaptosomes, to cause hemolysis of erythrocytes, and to dissipate voltage gradients across muscle membrane . The lycotoxins may play a dual role in spider-prey interaction, functioning both in the prey capture strategy as well as to protect the spider from potentially infectious organisms arising from prey ingestion . Spider venoms may represent a potentially new source of novel antimicrobial agents with important medical implications.

Genomics, 1997 Dec 15, 46(3), 472 - 5
Mapping of the gene encoding human beta-defensin-2 (DEFB2) to chromosome region 8p22-p23.1; Harder J et al.; We recently reported the isolation of human beta-defensin-2 (hBD-2), a novel epithelia-derived peptide antibiotic belonging to the beta-defensin family . hBD-2 is expressed in skin and epithelia of the airway system, where it is believed to contribute to its antimicrobial defense . By fluorescence in situ hybridization using a hBD-2 genomic DNA probe and subsequent fluorescence R-banding, the hBD-2 gene (HGMW-approved symbol DEFB2) was assigned to human chromosome region 8p22-p23.1 . PCR with a set of CEPH YAC clones spanning this chromosomal region revealed CEPH YACs 773G4, 920D12, and 820B4 to contain the hBD-2 gene . Relying on the preexisting physical maps of 8p22-p23.1, the hBD-2 gene was mapped in close proximity to D8S1993 (WI-9956) within the interval flanked by D8S552 and D8S1130 (CHLC.GATA25C10) . The fact that all currently described genes encoding defensins map to chromosome 8p21-pter suggests that a gene cluster in this chromosomal region may play a major role in antimicrobial defense.

Orv Hetil, 1997 Nov 30, 138(48), 3043 - 7
{Study of the cost-effectiveness of sequential antibiotic (ciprofloxacin) therapy}; Ludwig E et al.; A multicenter, prospective, randomized study was performed to compare the cost-effectiveness of parenteral antibiotic versus parenteral antibiotic + oral ciprofloxacin sequential therapy in the treatment of moderate and severe infections in hospitalized patients . After deciding on inclusion (n = 298), the patients were randomly allocated in group "A" (evaluable 120 cases) receiving only parenteral antibiotics, or in group "B" receiving parenteral antibiotic + oral ciprofloxacin from the 3.-5 . day of therapy on . The local physician decided on the starting parenteral therapy and the necessity of other therapeutic interventions, and in case of group "B" patients on the possibility of switching parenteral to oral therapy . The overall cure rate was 68% in group "A" and 82% in group "B" (improved 33 and 21, failure 5 and 1 cases resp.) . Of the direct costs in patients, care, the costs of antibiotic treatments based on purchase prices was compared: the cost of antibiotic treatment in group "B" was 32% less than in group "A", and the sequential therapy saved 9000 Ft/patient in average . In conclusion, ciprofloxacin proved to be an effective antimicrobial agent that can also be used in sequential therapy and the oral administration resulted in a significant save of money with the same therapeutic effectiveness.

Tierarztl Prax Ausg G Grosstiere Nutztiere, 1997 Aug, 25(5), 407 - 12
{Occurrence of Prototheca mastitis in dairy farms in Hesse}; Schlenstedt R et al.; During January 1994 and August 1996 from dairy farms in Hessia a total of 305,609 milk samples were investigated . Prototheca sp . as etiological agent of a mastitis was isolated from milk samples of seven dairy herds . According to our experiences and to several reports from various countries dealing with Prototheca infections in dairy herds, mastitis control programs should include Prototheca algae as potential pathogens . Mastitis due to this organism usually occurs in different semeiologies, one with clinical symptoms, and the other, more common type, as subclinical mastitis . In both cases, Prototheca organisms use to persist in the tissue of the mammary gland also during the dry period and antimicrobial treatment proves to be ineffective . Considering the wide distribution of these algae as saprophytes in the environment and in feces of several domestic animals, predisposing factors like a humid aerobic milieu and unsanitary milking conditions are necessary for Prototheca infections becoming manifest in the udder of dairy cows . Control measures should preferably stress the identification and removal of infected animals, in particular when the disease is sporadic in the herd . Due to the more questionable occurrence of spontaneous healing and the lack of an efficient drug, slaughtering of infected cows appears as a suitable method to eliminate the disease from the herd . Additionally, improvement of the hygiene status concerning feeding and milking management within a herd is as essential as in the control of other opportunistic udder pathogens.

Arch Otolaryngol Head Neck Surg, 1998 Jan, 124(1), 31 - 4
Management of rhinosinusitis in children: consensus meeting, Brussels, Belgium, September 13, 1996; Clement PA et al.; OBJECTIVES: To (1) provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs; (2) provide indications for microbiological, allergic, and immunologic assessment as well as for imaging studies; (3) suggest standard medical management with judicious use of antimicrobial agents; and (4) discuss indications for surgery . DATA SOURCES: Clinical studies and literature data relevant to the different topics of pediatric rhinosinusitis . CONCLUSIONS: Rhinosinusitis in children is a multifactorial disease in which the importance of several predisposing factors changes with increasing age . Continued study to obtain a better understanding of the disease and carefully controlled comparative evaluations of medical and surgical therapies are suggested.

Chest, 1998 Jan, 113(1), 142 - 6
The clinical benefit of in-hospital observation in 'low-risk' pneumonia patients after conversion from parenteral to oral antimicrobial therapy; Rhew DC et al.; OBJECTIVE: To assess the benefit of in-hospital observation in "low-risk" patients with community-acquired pneumonia . DESIGN: Retrospective review of data from a prospective study . SETTING: Teaching community hospital . PATIENTS: We studied 717 consecutive, adult patients admitted to the hospital for pneumonia . MEASUREMENTS AND RESULTS: One hundred forty-five patients were classified at low-risk for complications using previously studied criteria; 144 (99%) charts were available for review . Two patients had "obvious reasons for continued hospitalization" on the day of antibiotic conversion and were excluded . One hundred two patients were observed, and 40 were not observed in-hospital after switch to oral antibiotics . No patient from either group required medical intervention within 24 h after hospital discharge . Five "observed" patients (5%, 95% confidence interval {CI}, 2 to 11%) returned to the emergency department, three (3%; 95% CI, 0 to 9%) with respiratory complaints . Two (2%; 95% CI, 0 to 7%) "observed" patients were admitted to the hospital with recurrent pneumonia . One (3%; 95% CI, 0 to 13%) "not observed" patient returned to the emergency department with a nonrespiratory complaint and was not admitted . No patient from either group died within 30-day clinical follow-up . The length of stay for the "observed" and "not observed" groups was 98+/-33 h and 83+/-49 h, respectively . The difference in length of stay was 15 h (95% CI, 3 to 27) . CONCLUSIONS: In-hospital observation for low-risk patients admitted with community-acquired pneumonia after switch from parenteral to oral antibiotics is of limited benefit, and elimination of this practice could potentially reduce length of stay by almost 1 day per patient . This could translate into a cost savings of $57,200 for the 22-month study period . These results require prospective validation in a larger study.

Chest, 1998 Jan, 113(1), 131 - 41
A 1-year community-based health economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group; Grossman R et al.; OBJECTIVE: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period . DESIGN: Randomized, multicenter, parallel-group, open-label study . SETTING: Outpatient general practice . PATIENTS: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence) . MAIN OUTCOME MEASURES: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses . Patients completed the Nottingham Health Profile, St . George's Respiratory Questionnaire, and the Health Utilities Index . The parameters were recorded with each AECB and at regular quarterly intervals for 1 year . These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group . RESULTS: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care . The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50) . The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm . Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval {CI}, 0.91 to 1.58; p=0.19) . Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods . There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care . The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6) . The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932) . The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained . When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario) . CONCLUSIONS: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant . Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected . Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin . In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits . In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

J Biol Chem, 1997 Dec 19, 272(51), 32176 - 81
Specific, high affinity binding sites for an antifungal plant defensin on Neurospora crassa hyphae and microsomal membranes; Thevissen K et al.; Hs-AFP1, an antifungal plant defensin from seed of the plant Heuchera sanguinea, was radioactively labeled using t-butoxycarbonyl-{35S}L-methionine N-hydroxysuccinimidyl ester, resulting in a 35S-labeled peptide with unaltered antifungal activity . {35S}Hs-AFP1 was used to assess binding on living hyphae of the fungus Neurospora crassa . Binding of {35S}Hs-AFP1 was found to be competitive, reversible, and saturable with an apparent Kd of 29 nM and a Bmax of 1.4 pmol/mg protein . {35S}Hs-AFP1 also bound specifically and reversibly to microsomal membranes derived from N . crassa hyphae with a Kd of 27 nM and a Bmax of 102 pmol/mg protein . The similarity in Kd value between binding sites on hyphae and microsomes indicates that Hs-AFP1 binding sites reside on the plasma membrane . Binding of {35S}Hs-AFP1 to both hyphae and microsomal membranes could be competed to some extent by four different structurally related plant defensins but not by various structurally unrelated antimicrobial peptides . In addition, an inactive single amino acid substitution variant of the antifungal plant defensin Rs-AFP2 from Raphanus sativus seed was also unable to displace {35S}Hs-AFP1 from its binding sites, whereas Rs-AFP2 itself was able to compete with {35S}Hs-AFP1.

Eur J Pharmacol, 1997 Oct 8, 336(2-3), 211 - 7
The triterpenoid quinonemethide pristimerin inhibits induction of inducible nitric oxide synthase in murine macrophages; Dirsch VM et al.; Inducible nitric oxide synthase dependent production of nitric oxide (NO) plays an important role in inflammation . We investigated whether pristimerin ((20alpha)-3-hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-te traen-carboxylic acid-(29)-methylester), an antitumoral, antimicrobial as well as anti-inflammatory plant compound, has an effect on the inducible NO synthase system in lipopolysaccharide-activated RAW 264.7 macrophages . Pristimerin dose dependently (IC50: 0.2-0.3 microM) reduces nitrite accumulation, a parameter for NO synthesis, in supernatants of lipopolysaccharide-stimulated (1 microg/ml, 20 h) macrophages . This effect correlates with a reduced inducible NO synthase enzyme activity measured by conversion of {3H}L-arginine to {3H}L-citrulline and significantly lower levels of enzyme protein (Western blotting) in homogenates of cells cotreated with lipopolysaccharide and pristimerin (12 h) . Northern blot analysis and polymerase chain reaction (PCR) showed decreased inducible NO synthase mRNA levels in activated macrophages exposed to pristimerin (4 h) . Electrophoretic mobility shift assay (EMSA) demonstrated a markedly reduced binding activity of nuclear factor-kappa B (NFkappaB) in nuclear extracts of pristimerin-treated cells . These results suggest that pristimerin inhibits the induction of inducible NO synthase by a mechanism which involves inhibition of NFkappaB activation . This feature of pristimerin is likely to contribute to its anti-inflammatory activity.

Scand J Gastroenterol, 1997 Dec, 32(12), 1209 - 14
Highly effective second-line anti-Helicobacter pylori therapy in patients with previously failed metronidazole-based therapy; Lerang F et al.; BACKGROUND: In this study we compared the cure rates of two clarithromycin-based regimens in patients in whom anti-Helicobacter pylori therapy had previously failed . METHODS: Thirty-three patients were randomized to receive either regimen OAC (20 mg omeprazole, 750 mg amoxicillin, and 250 mg clarithromycin) or BTC (240 mg bismuth subcitrate, 750 mg oxytetracycline, and 250 mg clarithromycin), all twice daily for 10 days . A further 28 patients were all treated with OAC . Previously failed therapy included combinations of bismuth (B), omeprazole (O), tetracycline (T), metronidazole (M), amoxicillin (A), or clarithromycin (C) in BTM (n = 48), OAM (n = 13), OA (n = 7), OCM (n = 2), or BCM (n = 1) . H . pylori infection was confirmed by culture of biopsy specimens, and antimicrobial susceptibility testing was performed with the E test . RESULTS: H . pylori infection was cured in all patients (n = 18) with OAC and in 8 patients (53%) with BTC (P = 0.001) in the randomized group and in 27 patients (96%) receiving OAC in the open-label group . CONCLUSIONS: Ten-day OAC is highly effective and superior to BTC in patients in whom metronidazole-based treatment has previously failed.

Bone, 1998 Jan, 22(1), 33 - 8
In vitro sensitivity of the three mammalian collagenases to tetracycline inhibition: relationship to bone and cartilage degradation; Greenwald RA et al.; There are at least nine tetracycline (TC) analogs (both antimicrobial and nonantimicrobial) with documented capacity to inhibit, both in vitro and in vivo, the connective tissue degrading activity of matrix metalloproteinases (MMPs) . Of the three MMPs that can degrade native helical collagens, MMP-13 (initially identified as rat osteoblast and human breast cancer collagenase, and now known to also be expressed by human cartilage and bone cells) is the most sensitive to TC inhibition (IC50 values in vitro generally less than 1 microgram/mL); the TCs inhibit both the collagenolytic as well as the gelatinolytic activity of this enzyme . The IC50 for MMP-8 (neutrophil collagenase) in vitro ranges from 15 to 86 micrograms/mL depending on assay conditions and choice of TC, whereas inhibition of the fibroblast enzyme (MMP-1) generally requires levels in excess of 200 micrograms/mL (except for CMT-3) . The TC compounds that are highly effective against MMP-13 in vitro are also highly inhibitory of glycosaminoglycan release from interleukin-1-stimulated cartilage explants in culture . The current data correlate well with: (i) literature values for TC inhibition of bone resorption by isolated osteoclasts; (ii) inhibition by TCs of avian tibial resorption in organ culture; and (iii) the dramatic ability of TCs to inhibit bone destruction in many rat models (rats have only MMP-8 and MMP-13, and no MMP-1) . By carefully selecting a TC-based MMP inhibitor and controlling dosages, it should be possible to inhibit pathologically excessive MMP-8 and/or MMP-13 activity, especially that causing bone erosion, without affecting the constitutive levels of MMP-1 needed for tissue remodeling and normal host function; in this regard, three newly developed CMTs (especially CMT-8, and, to a lesser extent, CMT-3 and -7) appear to be most effective.

Am J Infect Control, 1997 Dec, 25(6), 513 - 9
Research utilization: adhesive bandage dressing regimen for peripheral venous catheters; VandenBosch TM et al.; BACKGROUND: This project used the process of research utilization to apply research knowledge to clinical practice for dressing peripheral intravenous (i.v.) catheters . METHOD: The project included (1) the review and synthesis of multiple research studies, (2) transformation of the research-based knowledge into a clinical protocol of use of adhesive bandage (AB) for dressing peripheral i.v . catheters, and (3) evaluation of the proportion of phlebitis as an outcome measure for comparison of peripheral i.v . catheter sites dressed with 2 x 2 inch gauze/tape or AB . Integral to the research utilization process was the use of planned change strategies . RESULTS: The proportion of phlebitis among peripheral i.v . catheters dressed with gauze/tape was 16.7% compared with 14.9% for AB . Antimicrobial ointment applied to the insertion site resulted in a higher proportion of phlebitis when used with an AB . CONCLUSION: This project used a research utilization framework to transfer research knowledge into clinical practice . To assure dissemination and implementation of the new practice, the use of ABs for dressing peripheral i.v.s was incorporated into hospital policy and procedure . In addition, the discontinuation of application of an antimicrobial ointment to peripheral i.v . sites was reinforced.

Semin Respir Infect, 1997 Dec, 12(4), 300 - 7
Limitations of diagnostic testing in the initial management of patients with community-acquired pneumonia; San Pedro GS et al.; Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality in the United States . The ideal of a simple diagnostic evaluation yielding a specific etiologic diagnosis allowing directed antimicrobial therapy remains elusive . Empiric therapy is justified as initial management, as the specific bacteriological etiology of most cases of CAP is usually unknown, and delaying therapy while attempting to find a diagnosis may be injurious to the patient . Guidelines have been developed to assist in the recognition and evaluation of CAP based on age and underlying medical illness as predictors of outcome . While these criteria are by no means perfect and cannot be applied to every individual, they offer a rational approach to the initial management of the patient.

Semin Respir Infect, 1997 Dec, 12(4), 308 - 21
Diagnostic testing to establish a microbial cause is helpful in the management of community-acquired pneumonia; Skerrett SJ; Antibiotic treatment for community-acquired pneumonia (CAP) can be specifically directed at an identified etiologic agent, or empirically formulated based on consideration of the likely pathogens according to the patient's age, underlying diseases, and clinical presentation . In recent years the empirical approach has become increasingly popular, and there is a growing trend away from efforts to make a microbiological diagnosis . This article reviews the tests that are currently available for the diagnosis of CAP, including stains, cultures, antigen-detection techniques, nucleic acid amplification, and serologies . Arguments then are presented in support of efforts to make a microbiological diagnosis . Clinical and radiographic features of CAP are not sufficiently distinctive to infer a specific microbial cause . Identification of the etiologic agent can be made in the majority of cases, and most microbiological diagnoses can be made rapidly with simple tests . The best opportunity to make an etiologic diagnosis is before antibiotics are administered . Identification of the microbial cause of pneumonia permits specific, narrow-spectrum antibiotic treatment that may be more effective, less toxic, and less expensive than empiric therapy . Microbiological data from individual patients contributes to understanding the local microbial epidemiology of CAP, including the local distribution of pathogens and their antimicrobial resistance patterns, information that is invaluable in the construction and modification of empiric treatment regimens . The reliance on empiric treatment engenders a false complacency, based on the erroneous assumption that broad-spectrum antibiotics will treat all cases of CAP . The unnecessary use of broad-spectrum antibiotic combinations in the empiric treatment of CAP contributes to the growing problem of antimicrobial resistance.

Semin Respir Infect, 1997 Dec, 12(4), 278 - 93
In nosocomial pneumonia, optimizing antibiotics other than aminoglycosides is a more important determinant of successful clinical outcome, and a better means of avoiding resistance; Schentag JJ et al.; In in vitro and animal models, antibiotics show good relationships between concentration and response, when response is quantified as the rate of bacterial eradication . The strength of these in vitro relationships promises their utility for dosage regimen design and predictable cure of infections such as nosocomial pneumonia . In spite of their intuitive logic, close relationships between dosage and bacterial eradication have not been easy to show in clinical studies of nosocomial pneumonia . Presumably, a variety of patient, disease, bacterial, and pharmacokinetic variables cloud these relationships in patients, and delay their elucidation in patient trials . Patients with serious infections like nosocomial pneumonia require bactericidal antimicrobial activity . Studies in our laboratory show that the minimum effective antimicrobial action is an area under the inhibitory titer (AUIC) of 125, in which AUIC is calculated as the 24 hour serum area under the curve (AUC) divided by the minimum inhibitory concentration (MIC) of the pathogen . This target AUIC may be achieved with either a single antibiotic or it can be the sum of AUIC values of two or more antibiotics . There is considerable variability in the actual AUIC value for patients when antibiotics are administered in their usual recommended dosages . Examples of this variance will be provided using aminoglycosides, fluoroquinolones, and beta-lactams . The achievement of minimally effective antibiotic action, consisting of an AUIC of at least 125, is associated with bacterial eradication in about 7 days for beta-lactams and quinolones . Adding an aminoglycoside to beta-lactams may produce a slight increase in their rate of bacterial killing in vivo, but because of their narrow therapeutic window, and the associated low doses in relation to MIC, there are situations in which the aminoglycosides may be unable to add sufficient additional AUIC . Antibiotic activity indices allow clinicians to evaluate individualized patient regimens . Furthermore, antibiotic activity is a predictable clinical endpoint with predictable clinical outcome . This value also is highly predictive of the development of bacterial resistance . Antimicrobial regimens that do not achieve an AUIC of at least 125 cannot prevent the selective pressure that leads to overgrowth of resistant bacterial subpopulations . The methods based on the determination of AUIC have clinical applicability in routine practice, through software developed for this purpose . These indices can assist with patient management strategies in a prospective manner because they can identify patients at high risk of therapeutic failure or acquired resistance early in therapy before therapy fails . Our studies show that calculations of AUIC can be used to prospectively target regimens to improve the chances of cure with nosocomial pneumonia and other serious infections . A clinical intervention team has been organized to optimize antimicrobial regimens as early in therapy as possible, to lower the high cost events such as failure and acquired bacterial resistance.

Am J Physiol, 1997 Dec, 273(6 Pt 2), R1870 - 7
Role of circulating endotoxin and interleukin-6 in the ACTH and corticosterone response to intraperitoneal LPS; Lenczowski MJ et al.; Peripheral administration of lipopolysaccharide (LPS) may activate the hypothalamus-pituitary-adrenal (HPA) axis by way of both neural and humoral mechanisms . We have investigated whether biologically active endotoxin appears in the general circulation after intraperitoneal administration of LPS (5 or 100 micrograms/kg) to rats and whether this is a prerequisite for activation of this HPA axis . Within 15 min, endotoxin appeared in the general circulation, whereas elevations of plasma adrenocorticotropic hormone (ACTH), corticosterone, and interleukin (IL)-6 concentrations were not detected until 90 min after LPS injection . At this time, a marked interindividual variation was observed in plasma concentrations of endotoxin, ACTH, corticosterone, and IL-6 . Elevated levels of plasma endotoxin were associated with elevated levels of ACTH, corticosterone, and IL-6 . Intravenous administration of the LPS antagonist cationic antimicrobial protein 18 (5 mg/kg), which did not affect cytokine production in the peritoneal cavity, markedly reduced plasma ACTH, corticosterone, and IL-6 levels after 5 micrograms/kg LPS . Our results suggest that circulating endotoxin is required for the activation of the HPA axis . They also favor a role for circulating IL-6 in this response.

FEMS Microbiol Lett, 1997 Dec 15, 157(2), 229 - 32
Novel bismuth compounds have in vitro activity against Helicobacter pylori; Midolo PD et al.; The increasing antimicrobial resistance in Helicobacter pylori has led to the search for new therapeutic agents . In this in vitro study, novel compounds combining bismuth with sialic acid inhibitors were investigated for bactericidal activity using time-kill methodology . The activity of these compounds was compared to bismuth subcitrate against a type strain and a clinical isolate of H . pylori . The compounds tested showed cidal activity which was related to the bismuth component of each drug . These compounds may offer a potential advantage over current bismuth preparations with the sialic acid inhibitor moiety interfering with adhesion of H . pylori to gastric epithelium.

Scand J Infect Dis, 1997, 29(5), 513 - 6
Susceptibility of Chlamydia pneumoniae to azithromycin and doxycycline: methodological aspects on the determination of minimal inhibitory and minimal bactericidal concentrations; Nystrom-Rosander C et al.; An in vitro assay for measuring and comparing the efficacy of different antimicrobial agents against Chlamydia pneumoniae was developed . Azithromycin, a representative of the new azalide group of antibiotics, and doxycycline were evaluated with respect to their antibacterial effect and capacity for intracellular killing under different experimental conditions . For both study drugs, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values increased significantly with longer bacterial preincubation time . The effect of different exposure times of antibiotics on the bacteria was also studied.

Scand J Infect Dis Suppl, 1997, 105, 24 - 31
Antimicrobial susceptibility testing in Sweden . IV . Quality assurance; Kahlmeter G et al.; The performance of susceptibility testing depends on high-quality material (disks and media), good laboratory practice (robust methodology and correct handling of material) and antimicrobial breakpoints being set in such a way that they allow for some intralaboratory variation . Thus, breakpoints must not divide homogeneous bacterial populations . Routine susceptibility testing should be checked with both internal and external quality control programs . The internal quality control should be designed to demonstrate the importance of minimizing random errors and to rapidly disclose systematic errors . This can be achieved either through the repeated testing of defined control strains or by systematic comparison of histograms of routine zone diameters with reference histograms supplied by the Swedish Reference Group for Antibiotics (SRGA and SRGA-M) . The SRGA-M offers an external quality control program which by its design also functions as an epidemiological surveillance program . The quality control programs are supported by an educational program for laboratory personnel.

Scand J Infect Dis Suppl, 1997, 105, 8 - 12
Antimicrobial susceptibility testing in Sweden . II . Species-related zone diameter breakpoints to avoid interpretive errors and guard against unrecognized evolution of resistance; Ringertz S et al.; The Swedish Reference Group for Antibiotics appointed a subcommittee on methodology (SRGA-M) in 1987 to investigate ways of defining interpretive breakpoints for antimicrobial susceptibility testing . The minimum inhibitory concentration (MIC) breakpoints for susceptibility categories are mainly based on pharmacological properties of the antibiotic, and they are, with few exceptions, valid for all species . However, for several species the MIC breakpoints have failed to distinguish strains with reduced susceptibility from normal susceptible strains . Disk diffusion is the routine method for susceptibility testing in Sweden . Studies of distribution of MICs and zone diameters for clinically important bacterial species have resulted in an emphasis on resistance rather than on susceptibility . The SRGA-M chose to place the zone diameter breakpoints close to the native (often susceptible) population of each species or group of related species . Such species-related zone diameter breakpoints used for susceptibility categories no longer correspond to the pharmacological MIC breakpoints, but divide each species into the fully susceptible (native) population and into those isolates/populations that have acquired a resistance mechanism, resulting in high- or low-grade resistance . By this method the risk of reports of false susceptibility is minimized and early detection of the emergence of antibiotic resistance is ensured.

Scand J Infect Dis Suppl, 1997, 105, 5 - 7
Antimicrobial susceptibility testing in Sweden . I . The work of the Swedish Reference Group for Antibiotics (SRGA and SRGA-M); Olsson-Liljequist B et al.; The Swedish Reference Group for Antibiotics (SRGA) is an expert committee within the Swedish Medical Society and has been working with different aspects of susceptibility testing of bacteria to antibiotics since 1978 . The emphasis has been on standardization of methodology, evaluation of the in vitro activity of new and old antibiotics, and the detection and significance of resistance mechanisms in bacteria . In the following a review is presented of the work conducted by the SRGA.

Planta Med, 1997 Dec, 63(6), 503 - 7
Antimicrobial activity of polyacetylenes from Bellis perennis and their synthetic derivatives; Avato P et al.; The chemical investigation of the essential oils from the aerial organs of Bellis perennis L., the common daisy, showed that polyacetylenes were one of the dominant class of compounds . The major constituents, methyl deca-4,6-diynoate and deca-4,6-diynoic acid, and their structural analogues, deca-4,6-diyne, dimethyl octa-3,5-diyne-1,8-dioate and deca-4,6-diyne-1,10-dioic acid, were synthesised and their antimicrobial activity evaluated . Only deca-4,6-diynoic acid and deca-4,6-diyne-1,10-dioic acid showed antimicrobial activity, being the two compounds mainly effective against Gram-positive and Gram-negative bacteria, respectively . Structure-activity relationships of the tested polyacetylenes are discussed.

Respirology, 1996 Jun, 1(2), 115 - 22
Diagnosis and treatment of bacterial pneumonia in Korea; Han YC et al.; Even with advancements in knowledge the problem of pneumonia will not be eliminated . It should be understood who is at risk, why such people develop pneumonia, what causes the pneumonia, and respiratory infection should be managed and prevented . The relative frequency of the isolation of various etiologic agents that cause bacterial pneumonia differ according to age group, geography, socio-economic status, underlying disease, time of year, and possible concomitant viral illnesses . Prompt identification of the causative agent is vital in the management of pneumonia . The present status of elucidating the etiologic agent is far from complete and recently, newer techniques using DNA probes and polymerase chain reactions were used for the identification of microbial pathogens . The timely use of appropriate systemic antibacterial therapy eradicates the pathogens . Considering the alterations of the etiologic agents of bacterial pneumonia and antibiotic susceptibilities, attention should be directed to the usage of antimicrobial agents in order to maximize the efficacy and the therapeutic implications.

Biopolymers, 1998, 45(1), 51 - 67
Structure of human salivary histatin 5 in aqueous and nonaqueous solutions; Raj PA et al.; The solution structure of human salivary histatin 5 (D-S-H-A-K-R-H-H-G-Y-K-R-K-F-H-E-K-H-H-S-H-R-G-Y) was examined in water (pH 3.8) and dimethyl sulfoxide solutions using 500 MHz homo- and heteronuclear two-dimensional (2D) nmr . The resonance assignment of peptide backbone and side-chain protons was accomplished by 2D total correlated spectroscopy and nuclear Overhauser effect (NOE) spectroscopy . The high JNH-C alpha H values (> or = 7.4 Hz), absence of any characteristic NH-NH (i, i + 1) or C alpha H-C beta H (i, i + 3) NOE connectivities, high d delta/dT values (> or = 0.004 ppm K-1) and the fast 1H/2H amide exchange suggest that histatin 5 molecules remain unstructured in aqueous solution at pH 3.8 . In contrast, histatin 5 prefers largely alpha-helical conformation in dimethyl sulfoxide solution as evident from the JNH-C alpha H values (< or = 6.4 Hz), slow 1H/2H exchange, low d delta/dT values (< or = 0.003 ppm K-1) observed for amide resonances of residues 6-24, and the characteristic NH-NH (i, i + 1) and C alpha H-C beta H (i, i + 3) NOE connectivities . All backbone amide 15N-1H connectivities fall within 6 ppm on the 15N scale in the 2D heteronuclear single quantum correlated spectrum, and the restrained structure calculations using DIANA suggest the prevalence of alpha-helical conformations stabilized by 19 (5-->1) intramolecular backbone amide hydrogen bonds in polar aprotic medium such as dimethyl sulfoxide . The interside-chain hydrogen bonding and salt-bridge type interactions that normally stabilize the helical structure of linear peptides in aqueous solutions are not observed . Histatin 5, unlike other naturally occurring antimicrobial polypeptides such as magainins, defensins, and tachyplesins, does not adopt amphiphilic structure, precluding its insertion into microbial membranes and formation of ion channels across membranes . Electrostatic (ionic type) and hydrogen bonding interactions of the positively charged and polar residues with the head groups of microbial membranes or with a membrane-bound receptor could be the initial step involved in the mechanism of antimicrobial activity of histatins.

Chem Pharm Bull (Tokyo), 1997 Dec, 45(12), 1970 - 4
Synthesis and antimicrobial characteristics of 4,4'-(alpha,omega-polymethylenedithio)bis(1-alkylpyridinium iodide)s; Okazaki K et al.; Bis-quaternary ammonium compounds (bis-QACs), 4,4'-(alpha,omega-polymethylenedithio)bis(1-alkylpyridinium iodide)s (4DTBP-m,n), which have 3 to 10 carbon atoms in the connecting methylene chain (m) and 8 to 18 carbon atoms of the N-alkyl chain (n), were synthesized . 4DTBP-6,12 exhibited a wide antimicrobial spectrum against gram-positive and gram-negative bacteria and fungi . The activity was stronger than those of N-dodecylpyridinium iodide (P-12), benzyldodecyldimethylammonium chloride and 2-(4-thiazolyl)benzimidazole . The bactericidal activities of 4DTBP-m,n were scarcely affected by the lengths of the alkyl chain and methylene chain . The bis-QAC that showed the highest activity was 4DTBP-6,8 (minimum inhibitory concentration (MIC) = 1.6 microM, minimum bactericidal concentration (MBC) = 2.6 microM), and its activity was about 10 times that of N-hexadecylpyridinium iodide (P-16), which was the most active in the P-n series . In addition, 4DTBP-6,12 showed a high bactericidal activity in the ranges of pH 5 to 8.5 and 10 to 40 degrees C, in contrast to mono-QACs . The bis-QACs synthesized in this study have excellent bactericidal properties.

J Am Acad Audiol, 1997 Dec, 8(6), 367 - 78
Disorders of the external auditory canal; Roland PS et al.; The normal anatomy and physiology of the external auditory canal is covered, followed by detailed descriptions of disorders and treatments of known and unknown etiology . Included are asteatosis, bacterial and fungal external otitis, bullous myringitis, allergic dermatitis, keratosis obturans, canal cholesteatoma, exostosis, osteoma, ceruminoma, basal and squamous cell carcinoma, and adenoma . A review of malignant external otitis is included with special emphasis on the expanding role of outpatient treatment and the use of oral antimicrobials.

Inflammation, 1997 Dec, 21(6), 655 - 65
Roxithromycin, clarithromycin, and azithromycin attenuate the injurious effects of bioactive phospholipids on human respiratory epithelium in vitro; Feldman C et al.; The effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the beat frequency and structural integrity of human ciliated respiratory epithelium were studied in vitro, in the presence or absence of polymorphonuclear leukocytes (PMNL), the antimicrobial agents, roxithromycin, clarithromycin, and azithromycin and the antioxidative enzymes catalase and superoxide dismutase (SOD) . All three PL caused dose-dependent slowing of ciliary beat frequency (CBF) and epithelial damage (ED) at concentrations > or = 1 microgram/ml, which were unaffected by inclusion of the antimicrobial agents and antioxidative enzymes . When epithelial strips were exposed to the combination of PMNL and PL, there was significant potentiation of ciliary dysfunction and ED, which was ameliorated by pretreatment of the PMNL with the antimicrobial agents or by inclusion of catalase, but not SOD . These results demonstrate that LPC, PAF, and lyso-PAF cause epithelial damage by direct mechanisms which are oxidant-independent, as well as by indirect mechanisms involving phagocyte-derived reactive oxidants . Macrolides and azalide antimicrobial agents may have beneficial effects on airway inflammation in asthma and microbial infections by protecting ciliated epithelium against oxidative damage inflicted by PL-sensitized phagocytes.

Res Vet Sci, 1997 Sep-Oct, 63(2), 157 - 60
In vitro susceptibilities of recent field isolates of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae to valnemulin (Econor), tiamulin and enrofloxacin and the in vitro development of resistance to certain antimicrobial agents in Mycoplasma hyopneumoniae; Hannan PC et al.; The in vitro activities of valnemulin (Econor) and two other antimicrobial agents were determined against recent field strains of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae using a broth microdilution method . Valnemulin showed exceptional activity against M hyopneumoniae (MIC90 0.0005 microgram ml-1) and M hyosynoviae (MIC range 0.0001 microgram ml-1 to 0.00025 microgram ml-1) field strains . Tiamulin was 100-fold less active (MIC90 0.05 microgram ml-1) and enrofloxacin 20-fold less active (MIC90 0.01 microgram ml-1) than valnemulin against M hyopneumoniae field isolates and 20-fold to 25-fold less active (MIC range 0.0025 microgram ml-1 to 0.005 microgram ml-1) and 400-fold to 500-fold less active (MIC range 0.05 microgram ml-1 to 0.1 microgram ml-1) respectively against M hyosynoviae field isolates . No significant resistance developed to valnemulin or tiamulin in the type strain of M hyopneumoniae (strain J) or in a recent field isolate (MEVT G23) exposed to 10 in vitro passages in broths containing these antibiotics . Only slight resistance to oxytetracycline was observed . High resistance to tylosin developed in both M hyopneumoniae strains within five to seven in vitro passages in tylosin-containing broth . Providing that similar results are obtained in vivo under field conditions, valnemulin may well prove to be effective in the treatment of enzootic pneumonia and acute polyarthritis in pigs.

Hum Exp Toxicol, 1997 Dec, 16(12), 727 - 32
Mitigation of nitrofurantoin-induced toxicity in the perfused rat lung; Bernard CE et al.; 1 . Nitrofurantoin is an antimicrobial agent which produces pulmonary toxicity via the redox cycling of the nitro group and its radical anion . This futile cycling triggers a complex series of events known collectively as oxidative stress . 2 . In the isolated perfused rat lung, nitrofurantoin induced a decrease in tissue levels of glutathione but not protein thiols by the end of the 180 min experiment . There was no decline in tissue levels of angiotensin converting enzyme (a marker of cell disruption) . However, edema was extensive as monitored in real time by weight gain (2.71 +/- 0.56 g vs 0.63 +/- 0.53 g in control, P < 0.05, n = 4) and lung mechanical functioning . The edema was matched by an increase in lavage proteins (85 +/- 15 mg vs 16 +/- 9 mg in controls, P < 0.05, n = 4) . Electron microscopic examination of tissue indicated that the endothelial cells were detached from the basement membrane which would account for the edema . 3 . Co-infusion of penicillamine, N-acetylcysteine or N-(2-mercaptopropionyl)-glycine which can protect tissue from oxidative stress failed to mitigate NFT-induced edema . Allopurinol, an inhibitor of xanthine oxidase and a metal chelator, significantly decreased weight gain but did not prevent the loss of glutathione . These results suggested that allopurinol was not blocking metabolic activation of NFT by xanthine oxidase but scavenging metal cations which can initiate and/or propagate the oxidative stress cascade . 4 . We concluded that, in the isolated perfused rat lung, the classic pathway of oxidative stress induced by NFT is interrupted at the stage of GSH loss . These experiments demonstrated that organ function was compromised more than the individual cells . They also suggested that allopurinol may prove beneficial in modulating NFT pulmonary toxicity.

Burns, 1997 Aug, 23(5), 387 - 91
A new silver sulfadiazine water soluble gel; Gear AJ et al.; Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds . It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application . The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application . The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188 . The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing . The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation . In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day . The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds . The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.

Curr Opin Biotechnol, 1997 Dec, 8(6), 757 - 62
Innovative approaches to novel antibacterial drug discovery; Trias J et al.; Increasing antibiotic resistance in microorganisms and new emerging pathogens have become a major problem in our society . Rising to satisfy this urgent medical need is a recent confluence of powerful new drug discovery technologies: combinatorial chemistry; sequence and functional genomic analysis; and novel methods of high-throughput screening . The combination of these technologies will bring to bear untapped power in the search for new antimicrobials.

Ann Trop Paediatr, 1997 Sep, 17(3), 245 - 51
Childhood pneumococcal bacteraemia in Riyadh, Saudi Arabia; Kambal AM et al.; Forty-nine children with pneumococcal bacteraemia seen during a 5-year period (1 January 1991 to 31 December 1995) at King Khalid University Hospital were studied . The majority (61.2%) were under 2 years of age . The focus of infection was pneumonia, pharyngitis or undetermined in 28.6%, 18.4% and 20.4%, respectively . Diseases that had probably predisposed them to pneumococcal bacteraemia (mainly nephrotic syndrome) were encountered in 24.5% of cases . Forty-five per cent of the cases occurred during the summer season and in 29% the disease was nosocomially acquired . No death was recorded in this series and the reasons for this are discussed . Detection of pneumococcal antigens from blood taken for culture was successful in 96% of cases; this test is important in the diagnosis of pneumococcal bacteraemia in partially treated patients . Antimicrobial susceptibility testing showed 20.4% of the isolates to be relatively penicillin-resistant . Resistance to other antimicrobial agents was also recorded and multiple resistance was noted in 22% of isolates . There was a significant difference between the ceftriaxone MIC of the relatively penicillin-resistant strains compared with penicillin-sensitive strains . The emergence and the steady increase in the numbers of relatively penicillin-resistant pneumococcal strains in Saudi Arabia during the last 10 years are discussed.

Mol Pharmacol, 1997 Dec, 52(6), 1081 - 6
In vivo production of nitric oxide in rats after administration of hydroxyurea; Jiang J et al.; The metabolism of nitrovasodilators such as glyceryl trinitrate and nitroprusside provides the active moiety of these drugs (that is, nitric oxide) . This process is not limited to the known nitrovasodilators, but also occurs with nitroaromatic antimicrobials . Here we report that the administration of hydroxyurea, an antitumor drug, to rats at pharmacological doses formed detectable nitrosyl hemoglobin, which increased with dose . At higher doses, nitrosyl hemoprotein complexes could also be detected in liver tissue . {15N}hydroxyurea was synthesized and compared with {14N}hydroxyurea . These observations verified that nitric oxide detected as nitrosyl hemoglobin or nitrosyl hemoprotein complexes in rats was the result of the metabolism of hydroxyurea . The time course and dose-dependence of nitric oxide generation were also investigated . Hydroxyurea's antineoplastic activity is caused by its direct action on ribonucleotide reductase, the rate-limiting enzyme in DNA synthesis . Because nitric oxide also inhibits ribonucleotide reductase, this metabolite may supplement this action of hydroxyurea . In addition, the known ability of hydroxyurea to ease the pain of sickle cell anemia patients may be the result of vasodilation by the drug-derived nitric oxide.

Infect Immun, 1998 Jan, 66(1), 5 - 10
Mannose induces the release of cytopathic factors from Acanthamoeba castellanii; Leher H et al.; Acanthamoeba keratitis is a chronic inflammatory disease of the cornea which is highly resistant to many antimicrobial agents . The pathogenic mechanisms of this disease are poorly understood . However, it is believed that the initial phases in the pathogenesis of Acanthamoeba keratitis involve parasite binding and lysis of the corneal epithelium . These processes were examined in vitro, using Acanthamoeba castellanii trophozoites . Parasites readily adhered to Chinese hamster corneal epithelial cells in vitro; however, parasite binding was strongly inhibited by mannose but not by lactose . Although mannose prevented trophozoite binding, it did not affect cytolysis of corneal epithelial cells . Moreover, mannose treatment induced trophozoites to release cytolytic factors that lysed corneal epithelial cells in vitro . These factors were uniquely induced by mannose because supernatants collected from either untreated trophozoites or trophozoites treated with other sugars failed to lyse corneal cells . The soluble factors were size fractionated in centrifugal concentrators and found to be > or = 100 kDa . Treatment of the supernatants with the serine protease inhibitor phenylmethylsulfonyl fluoride inhibited most, but not all, of the cytopathic activity . These data suggest that the binding of Acanthamoeba to mannosylated proteins on the corneal epithelium may exacerbate the pathogenic cascade by initiating the release of cytolytic factors.

Pathology, 1997 Nov, 29(4), 411 - 4
Antimicrobial resistance testing of Helicobacter pylori: a comparison of Etest and disk diffusion methods; Midolo PD et al.; Routine antimicrobial resistance testing of Helicobacter pylori is more commonly performed since the correlation between metronidazole resistance and failure to eradicate using this drug, has been made . While resistance testing of H . pylori by Etest is simple to perform, it is expensive compared to disk diffusion methods . In this study the Etest was compared with a modified Kirby-Bauer disk diffusion (NCCLS) method for routine resistance screening of H . pylori . Fifty one pre-treatment isolates were tested against amoxycillin, metronidazole, tetracycline and erythromycin by both Etest and disk diffusion using NCCLS guideline strength disks . Clarithromycin was tested by Etest only . Nitroimidazole and macrolide resistance were detected using the modified Kirby-Bauer disk diffusion method which correlated with Etest minimum inhibitory concentration (MIC) . Resistance rates were 49% for metronidazole and 8% for clarithromycin . Cross resistance occurs with macrolides against H . pylori and allows testing of erythromycin to predict resistance to clarithromycin . The very low MICs obtained with H . pylori against amoxycillin and tetracycline require the use of Etest or lower strength disk methods to be used.

Biochemistry, 1997 Dec 9, 36(49), 15081 - 8
Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase in complex with NADH and the inhibitor 2,6-pyridinedicarboxylate; Scapin G et al.; Dihydrodipicolinate reductase catalyzes the NAD(P)H-dependent reduction of the alpha,beta-unsaturated cyclic imine dihydrodipicolinate to form the cyclic imine tetrahydrodipicolinate . The enzyme is a component of the biosynthetic pathway that leads to diaminopimelate and lysine in bacteria and higher plants . Because these pathways are unique to microorganisms and plants, they may represent attractive targets for new antimicrobial or herbicidal compounds . The three-dimensional structure of the ternary complex of Escherichia coli dihydrodipicolinate reductase with NADH and the inhibitor 2,6-pyridinedicarboxylate has been solved using a combination of molecular replacement and noncrystallographic symmetry averaging procedures and refined against 2.6 A resolution data to a crystallographic R-factor of 21.4% (Rfree is 29.7%) . The native enzyme is a 120 000 molecular weight tetramer of identical subunits . The refined crystallographic model contains a tetramer, three molecules of NADH, three molecules of inhibitor, one phosphate ion, and 186 water molecules per asymmetric unit . Each subunit consists of two domains connected by two flexible hinge regions . While three of the four subunits of the tetramer have a closed conformation, in which the nicotinamide ring of the cofactor bound to the N-terminal domain and the reducible carbon of the substrate bound to the substrate binding domain are about 3.5 A away, the fourth subunit is unliganded and shows an open conformation, suggesting that the enzyme undergoes a major conformational change upon binding of both substrates . The residues involved in binding of the inhibitor and the residues involved in catalysis have been identified on the basis of the three-dimensional structure . Site-directed mutants have been used to further characterize the role of these residues in binding and catalysis . A chemical mechanism for the enzyme, based on these and previously reported data, is proposed.

Eur J Emerg Med, 1994 Jun, 1(2), 104 - 9
Infective endocarditis: prevention, diagnosis and management; Pierard LA et al.; Infective endocarditis remains an important problem and the means of prevention are still insufficient . The causal bacteria have changed very little, but the incidence of nosocomial infections and endocarditis complicating intravenous drug abuse are increasing . The distinction between subacute and acute clinical presentations remains appropriate . Cardiac and neurological complications are frequent and carry a high risk of mortality . The diagnosis is obtained by the integration of clinical data and the results of blood cultures . Echocardiography is extremely useful for detecting vegetations, and for assessing the haemodynamic consequences and specific cardiac complications . Risk stratification can be obtained by correct integration of multiple parameters . The causal agent should be identified before the initiation of antimicrobial therapy . Surgery is frequently required, and should be performed rapidly when indicated.

Infect Dis Clin North Am, 1997 Dec, 11(4), 889 - 903
The impact of antimicrobial resistance on the treatment of sexually transmitted diseases; Erbelding E et al.; The focus of this article is to review the development of antimicrobial resistance among several sexually transmitted diseases (STDs) and to discuss the frequency and mechanisms of resistance and recommendations for treatment of selected STDs in which resistance to certain antimicrobial agents has increased . For a number of STDs, such as Chlamydia trachomatis and syphilis, no evidence of antimicrobial resistance has developed over the years, although management of these diseases, such as in the case of pelvic inflammatory disease or syphilis in HIV-infected individuals, requires intensive treatment and follow-up to ensure effectiveness of treatment.

Infect Dis Clin North Am, 1997 Dec, 11(4), 803 - 12
The potential for clinical guidelines to impact appropriate antimicrobial agent use; Gross PA; Practice guidelines can help clinicians and microbiologists improve the quality and efficiency of health care . Numerous areas are in need of guideline development and development of quality improvement programs . These areas include antibiotic control, duration of antibiotic administration, use of narrowest spectrum, least toxic, lowest cost-effective antibiotic, use of rapid diagnostic tests, management of outpatient intravenous antibiotics, antibiotic prophylaxis for surgery, switching from intravenous to oral antibiotics, antibiotic selection for special situations, diagnosis of Lyme disease, and several other topics . IDSA, SHEA, CDC, NIH, and other organizations are cooperating to develop these guidelines.

Infect Dis Clin North Am, 1997 Dec, 11(4), 785 - 802
Laboratory issues in the detection and reporting of antibacterial resistance; Jorgensen JH; The emergence of antimicrobial resistance among several common bacterial pathogens requires that clinical microbiology laboratories have the ability to promptly and accurately recognize resistance in patients' isolates . Laboratories have several options for performing routine susceptibility testing, including the broth microdilution procedure (with or without instrumentation for test reading), automated instrument systems that provide rapid results, antibiotic gradient diffusion, and disk diffusion procedures . In addition, there are definitive screening tests capable of recognizing resistance to drugs of choice among several common bacterial species based on single drug concentration tests or rapid spot tests . The likely emergence of still newer resistance mechanisms will provide a challenge to clinical microbiologists to devise accurate, yet cost-effective strategies for use in the future.

Infect Dis Clin North Am, 1997 Dec, 11(4), 767 - 83
Surveillance for the emergence and dissemination of antimicrobial resistance in bacteria; Sahm DF et al.; Effective surveillance of antimicrobial-resistant bacteria is important for developing rational empiric therapy guidelines and for guiding public health efforts to control and prevent the spread of infective agents . Surveillance must include a timely and thorough review of the test results generated in clinical microbiology laboratories because this data serves as the core of surveillance activities . Besides ensuring data accuracy and optimizing detection of emerging resistance, the role of clinical microbiology also includes supporting the production of informative surveillance reports, providing laboratory resources for outbreak investigations, and monitoring the performance of commonly used susceptibility testing methods . Once the accuracy of susceptibility results has been validated, the data are used by public health agencies and professional societies to monitor resistance trends on a local, state, national, and international level . This information is also used to develop policies for prudent antimicrobial use locally and nationally.

Infect Dis Clin North Am, 1997 Dec, 11(4), 757 - 65
The impact of antimicrobial use on the emergence of antimicrobial-resistant bacteria in hospitals; Gaynes R; Abundant evidence suggests a relationship between antimicrobial resistance and use, including models, consistent associations between resistance and antimicrobial use in hospitals, concomitant variation in resistance as antimicrobial use varies, and a dose-response relationship for many pathogen/antimicrobial combinations . Much of the evidence is from studies performed in single hospitals . Most multicenter studies on resistance have not included data on antimicrobial usage . Despite this substantial body of evidence, some studies have not demonstrated an association between antimicrobial resistance and use, suggesting other contributing factors such as cross transmission, interhospital transfer of resistance, a community contribution to resistance, or a complex relationship between resistance and the use of a variety of antimicrobials . Understanding the problem of antimicrobial resistance in a hospital cannot be achieved without knowledge of the hospital's pattern of antimicrobial use.

J Antimicrob Chemother, 1997 Nov, 40(5), 653 - 7
Antimicrobial interference of a subinhibitory concentration of azithromycin on fimbrial production of Porphyromonas gingivalis; Lo Bue AM et al.; The first pathogenic mechanism of Porphyromonas gingivalis, which is mainly responsible for adult periodontal diseases, is the attachment of fimbriae appendages to oral epithelial cells . The ability of a subinhibitory concentration of azithromycin to inhibit the expression of fimbriae in various strains of P . gingivalis isolated was investigated . A one-eighth subinhibitory concentration of azithromycin was evaluated in vitro . The antibiotic was active in 75% of P . gingivalis strains isolated, judged by both electrophoresis and transmission electron microscopy . The results indicate that the subinhibitory concentration of azithromycin is capable of blocking the pathogenic mechanism of P . gingivalis in vitro, and, therefore, can be used in vivo as a treatment for recurrent periodontitis.

Pharmacoeconomics, 1998 Feb, 13(2), 191 - 222
Chlamydia trachomatis in adolescents and adults . Clinical and economic implications; Marra CA et al.; The aim of this article is to provide an overview of the epidemiology, diagnosis, screening and pharmacotherapy of Chlamydia trachomatis infections in adolescents and adults, together with a critical review of economic studies published on this topic . C . trachomatis continues to produce enormous social and economic consequences despite advances in prevention, screening and treatment . Both infected men and women are at risk of developing sequelae, although women tend to have more serious complications . Several strategies are available for diagnosis and screening . In populations with a high prevalence of disease, DNA-amplification assays may be the most cost-effective approach for diagnosis and screening . Empirical treatment of all patients is also cost effective; however, it may not be feasible for all health systems . A single dose of azithromycin is the most cost-effective antimicrobial agent for treatment of C . trachomatis infection.

Antimicrob Agents Chemother, 1997 Dec, 41(12), 2766 - 9
Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics; Waters B et al.; In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment . It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain . We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development.

Antimicrob Agents Chemother, 1997 Dec, 41(12), 2634 - 9
Antimicrobial susceptibility testing of 230 Helicobacter pylori strains: importance of medium, inoculum, and incubation time; Hartzen SH et al.; No standardized method of susceptibility testing for Helicobacter pylori is currently available, so before a large agar dilution study comprising 230 H . pylori strains belonging to more than 80 genetically different groups was initiated, we performed a relatively small preliminary study to determine the influences of medium, inoculum density, and incubation time . Seven media were investigated and were primarily evaluated on the basis of their abilities to support growth both semiquantitatively and qualitatively; Iso-Sensitest agar supplemented with 10% horse blood was found to be well suited for the purpose; this was closely followed by Mueller-Hinton agar with 10% horse blood, Mueller-Hinton with 10% sheep blood, and finally, 7% lysed horse blood agar . Investigations of two inoculum densities and two incubation times resulted in recommendations for the use of 10(9) CFU/ml (10{6} CFU/spot) as the inoculum and 72 h as the incubation time . A modest inoculum effect was noted for amoxicillin and metronidazole . By the methodology derived from our preliminary study, the susceptibilities of 230 H . pylori strains to six antibiotics were subsequently determined . The results were generally in accord with those of others, and apart from metronidazole, the MIC of which for approximately 25% of the strains tested was >8 microg/ml, resistance was low in Denmark . The situation might, however, quickly change when and if the number of indications for antibiotic therapy for H . pylori infections increase . Consequently, susceptibility testing of all H . pylori strains is recommended in order to survey the development of resistance, and in our hands the described methodology was relatively easy to perform and the results were easy to read.

J AOAC Int, 1997 Nov-Dec, 80(6), 1374 - 80
Improvements in amperometric detection of sulfite in food matrixes; Wygant MB et al.; Sulfite is added to foods as an antimicrobial, antibrowning agent, or antioxidant . It also can occur naturally, and is often used in the production of beer and wine . For years the standard methodology for determination of sulfite in foods has been the Monier-Williams method, which is a combination of acid distillation and titration . Recently, AOAC adopted a chromatographic method based on a method developed by Kim and Kim for the determination of sulfite . The method combines ion exclusion chromatography with direct-current (DC) amperometric detection to provide more convenient and accurate quantitation of sulfite . However, fouling of the platinum working electrode results in a rapid decrease in method sensitivity . As a result, standards must be injected before and after every sample, and the electrode must be polished frequently to maintain adequate detection limits . Pulsed amperometric detection overcomes electrode fouling problems by repeatedly and continuously applying cleaning potentials to the working electrode . Using this technique, a reproducible electrode surface can be maintained, and injection-to-injection repeatability is greatly improved . A comparison of method performance for both DC and pulsed amperometric detection is presented . Also investigated was the stability of sulfite samples at varying pH, and in the presence or absence of a preservative.

Harefuah, 1997 Oct 2, 133(7-8), 284 - 6, 335
{Gradenigo syndrome and cavernous sinus thrombosis in fusobacterial acute otitis media}; Hananya S et al.; In this era of antimicrobial medication, intracranial complications following otitis media are rare . We present a 5-year-old boy who suffered from petrositis (Gradenigo syndrome) and cavernous sinus thrombosis as combined complications of acute otitis media caused by fusobacteria . The diagnosis was made using imaging methods suited to the various structures of the skull . Cure was achieved by prolonged conservative treatment with antibiotics, with gallium scan for evaluation of the bone inflammation.

Int J Oral Maxillofac Surg, 1997 Dec, 26(6), 450 - 4
Treatment of chronic suppurative osteomyelitis of the mandible; van Merkesteyn JP et al.; Chronic suppurative osteomyelitis of the mandible is often considered difficult to treat and may lead to refractory osteomyelitis . Sixteen patients with chronic suppurative osteomyelitis of the mandible were treated with a relatively simple protocol, consisting of sequestrectomy or decortication and i.v . antimicrobial therapy for one week, followed by oral penicillin for three weeks . Only one case showed recurrence of symptoms, which was treated successfully in a second session . It is concluded that combined surgical and antimicrobial therapy should be sufficient to cure most cases of chronic suppurative osteomyelitis of the mandible.

Immunol Rev, 1997 Oct, 159, 49 - 67
Complement receptors in HIV infection; Speth C et al.; The complement system plays an important role in the antimicrobial defense of the organism . Its components recognize a large variety of pathogens and target them for destruction, either directly by formation of a membrane attack complex or indirectly by recruiting phagocytic cells . In addition, it has several functions in cell activation, clearance of immune complexes, control of inflammatory reactions, chemotaxis and autoimmunity . For mediation of all these tasks of the complement system, complement receptor molecules on the cell surface play a key role . Current knowledge on structure, function, signal transduction and associated molecules is briefly summarized here . The role of complement receptors for human immunodeficiency virus (HIV)-associated pathogenesis is ambiguous and varies depending on cell type . On the one hand, complement receptors support the infected host to manage HIV infection and to defend itself, at least partially, against viral spreading throughout the organism . Such complement receptor-mediated supporting mechanisms are activation of immune cells and lysis of viral particles and infected host cells . On the other hand, HIV employs complement receptors to intrude more easily into various cell types, to become localized into lymph follicles and to activate viral replication in latently infected cells . This review summarizes the complex interaction of virus and complement receptors in HIV infection for different cell types.

Ann Pharmacother, 1997 Dec, 31(12), 1521 - 3
Propofol and postoperative infections; Sklar GE; The package insert for propofol states in several places the importance of strict aseptic technique in the preparation and handling of the drug, and the potential for infection if these procedures are not followed . In the US, the product has been reformulated to contain disodium edetate 0.005% as a microbial growth retardant to inhibit the growth of microorganisms in the event of accidental contamination . However, this new formulation is not considered an antimicrobially preserved product under USP standards . What effect, if any, this has had on the risk of postoperative infections is not known . Strict aseptic technique is still required when handling the new formulation . When propofol is used as an anesthetic, it is recommended that the dose be prepared just prior to administration, and that the infusion be completed within 6 hours after the ampul or vial is opened . Any unused portion of propofol must be discarded at the end of the procedure or at 6 hours, whichever occurs sooner . In the ICU, if propofol is administered directly from its original container, the tubing and any unused portion must be discarded after 12 hours . If propofol is transferred to another container, administration lines and unused drug should be discarded after 6 hours . The occurrence of postoperative infections is usually thought to be related to the surgeon or the surgical procedure . However, based on the available microbiologic and clinical evidence, the use of propofol appears to be an additional risk factor . Hospital personnel involved in the preparation and handling of propofol must be educated on, and adhere to, the recommendations outlined by the manufacturer to prevent further outbreaks of infections.

J Exp Med, 1997 Dec 1, 186(11), 1885 - 96
A novel antioxidant gene from Mycobacterium tuberculosis; Ehrt S et al.; Among the major antimicrobial products of macrophages are reactive intermediates of the oxidation of nitrogen (RNI) and the reduction of oxygen (ROI) . Selection of recombinants in acidified nitrite led to the cloning of a novel gene, noxR1, from a pathogenic clinical isolate of Mycobacterium tuberculosis . Expression of noxR1 conferred upon Escherichia coli and Mycobacterium smegmatis enhanced ability to resist RNI and ROI, whether the bacteria were exposed to exogenous compounds in medium or to endogenous products in macrophages . These studies provide the first identification of an RNI resistance mechanism in mycobacteria, point to a new mechanism for resistance to ROI, and raise the possibility that inhibition of the noxR1 pathway might enhance the ability of macrophages to control tuberculosis.

Vet J, 1997 Nov, 154(3), 233 - 41
Comparison of carprofen and flunixin meglumine as adjunctive therapy in bovine respiratory disease; Balmer TV et al.; In an open, controlled, multi-centre clinical field trial, seven 'naturally occurring' outbreaks of acute febrile (rectal temperature > or = 39.5 degrees C) respiratory disease in housed calves were treated with a single antimicrobial agent, and either the non-steroidal anti-inflammatory drug (NSAID) carprofen (n = 95) or flunixin meglumine (n = 92) on an alternate basis . Carprofen was administered as a single subcutaneous injection at a mean dosage of 1.4 mg kg-1 (range 1.2 to 1.9 mg kg-1) body weight on the first day and flunixin meglumine by intravenous injection at a mean dosage of 2.0 mg kg-1 (range 1.2 to 2.6 mg kg-1) body weight on the first 3 consecutive days . All calves were examined clinically immediately prior to initial treatment and on three occasions up to 1 week after the end of treatment . There were no statically significant differences between NSAID groups in reduction of clinical parameters between examinations, or in overall efficacy . This trial demonstrated that a single dose of carprofen was equally effective as three daily doses of flunixin meglumine as adjunctive therapy to antimicrobial treatment in acute respiratory disease in calves.

Plast Reconstr Surg, 1997 Nov, 100(6), 1442 - 51
Prospective outcome analysis of a protocol for the surgical and rehabilitative management of burns to the hands; Barillo DJ et al.; Treatment protocols for the management of burned hands are essential for integrating team efforts and achieving optimal functional results . Standard protocols are especially useful during mass casualty incidents, when the admission of multiple patients with large burns and/or associated injuries may reduce the priority usually accorded the hands . We prospectively evaluated a surgical and rehabilitative treatment protocol for burned hands during a mass casualty incident, after which 43 burn patients with 82 burned hands were admitted to one burn center . Soft-tissue management was individualized to achieve, if possible, wound closure within 14 days, and included the use of topical antimicrobials, cutaneous debridement and/or tangential excision, biologic dressings, and split-thickness autografts . Range of motion therapy was based on daily measurement of active motion of the metacarpophalangealjoints . Static splinting alternating with continuous passive motion every 4 hours was utilized for sedated patients . Continuous passive motion alternating with active ranging and night splinting was utilized for metacarpophalangeal flexion <70 degrees . Active ranging and progressive resistance was utilized for metacarpophalangeal flexion > or =70 degrees . Sixty-four hands required excision and grafting, with 89 percent having at least one autografting procedure completed by postburn day 16 . Total active motion of the hands treated averaged 220.6 degrees on discharge and 229.9 degrees at 3 months after injury . Mean hand grip strength was 60.8 pounds at discharge and 66.0 pounds at 3 months after injury . Adherence to a standard hand burn protocol resulted in timely wound coverage and recovery of hand function for a large group of patients treated at a single burn facility after a mass casualty incident.

Arch Virol Suppl, 1997, 13, 67 - 82
Rapid molecular detection of microbial pathogens: breakthroughs and challenges; Pillai SD; Microbiological contamination of foods and drinking water is a global problem, and a significant amount of expense is being incurred as a result of such contamination . The microorganisms associated with almost half of all disease outbreaks still go unidentified, primarily as a result of inadequate monitoring and surveillance . Though significant improvements have been made in refining molecular methods for detecting infectious agents, a majority of these methods are being employed only on clinical samples where pathogen densities are much higher than those found in environmental and food samples . Comparative evaluations of the various protocols in terms of cost, sensitivity, specificity, speed, and reproducibility need to be undertaken so that the true applicability of these methods can determined . In the future, molecular methods, especially gene amplifications and in situ hybridizations, will find increasing applications in the differentiation of viable and non-viable organisms, in predicting antimicrobial resistance, and in the identification and characterization of unculturable microorganisms . Though molecular detection methods will not totally replace conventional methods, they will significantly enhance our ability to detect microbial pathogens rapidly.

Jpn J Antibiot, 1997 Oct, 50(10), 821 - 8
{Initial treatment at an outbreak of E . coli O-157:H7 infection: especially with respect to therapy in the emergency}; Chisaki T et al.; An outbreak of O-157:H7 diarrheal illnesses occurred in junior schools of Sakai-city, Osaka prefecture, in last July, 1996 . At the beginning of the outbreak, many patients rushed to outpatient clinics . From the practical experiences, we examined the necessity of fluid therapy in patients regarding their initial clinical features . The risk factors for development of HUS were noted as presence of fever, WBC counts of more than 10,000/microliter and more than 1.0 mg/dl of CRP . During the prodoromal illness, administration with available antimicrobial agents would be advisable for high risk patients, while it would yet be remain to be further investigated . The majority of the patients with clinical manifestations showed neither signs for dehydration nor electrolyte abnormalities based on the blood examination data and biochemical analysis of the serum . Therefore, the fluid therapy did not appear necessary for majority of patients except a few high risk patients, when outpatient clinics were crowded with emergency patients.

Schweiz Arch Tierheilkd, 1997, 139(5), 210 - 6
{Surgical treatment of carpal hygroma in cattle: 17 cases (1990-1994)}; Piguet M et al.; This retrospective study describes the case reports of 17 cattle suffering from precarpal hygroma, admitted to the clinic for food animals and horses, University of Berne, between 1990 and 1994 . The following criteria were evaluated: sex, age, and bodyweight, case history, clinical findings at admission, surgical technique, aftercare, and short- and long-term results . The hygroma was congenital in 3 cases and acquired at the age of 2 to 84 months in 14 cases . Characteristic clinical findings at admission were a non painful, fluctuating, well delineated swelling of the precarpal area with a maximal diameter of 6 to 20 cm, which did not provoke any lameness . Treatment consisted of surgical excision of the bursa . Surgery was performed under general anesthesia with the animal in lateral recumbency and the affected limb positioned uppermost . After placing a tourniquet proximal to the carpal joint, routine preparation and draping of the surgical field, the bursa was resected completely, a penrose drain introduced, and primary wound closure attempted . Aftercare consisted of parenteral antimicrobial treatment and immobilisation of the affected limb with a full-limb splint bandage to prevent wound dehiscence and seroma formation . Primary wound healing was achieved in all cases . At the time of long-term follow-up evaluation, 4 to 48 months after surgery, telephone conversation with the owners revealed uncomplicated healing in 16 cases . In one case, recurrence of the hygroma had occurred a few weeks after surgical excision had been performed.

Bull Soc Pathol Exot, 1997, 90(3), 192 - 5
{Stability and antimicrobial effectiveness of Javel water in a tropical hospital environment}; Ballereau F et al.; A sodium hypochlorite solution (NaClO) containing 0.5% w/v of available chlorine (0.5% Cl2 or 5000 ppm) is a good and cheap solution for disinfecting material used to medical care . It is effective against bacteria, fungi and viruses . It is easy to prepare . It can be a good solution for antisepsis and disinfection in dispensaries in developing countries . However, it is not always easy to keep it in adequate conditions . That's the reason why we have evaluated the durability of such a solution of NaClO exposed to disadvantageous factors, specially daylight and air, and its antibacterial effectiveness . In this study, after exposure of NaClO containing 4350 ppm of available chlorine to these adverse conditions, the final concentration of NaClO was 2300 ppm of available chlorine and was found effective for decontamination of medical material . A protocol for conservation and use of a sodium hypochlorite solution (0.5% Cl2) in dispensaries of developing countries is proposed.

Enferm Infecc Microbiol Clin, 1997 Oct, 15 Suppl 3, 33 - 40
{Antibiotic policy in intensive care}; Alvarez Lerma F; The use of antibiotics takes places by following a series of norms, which are called the antibiotics policy . The importance of their correct use is based on the influence which the antimicrobial agents may have on the development of resistance by the endogenous agents in a specific hospital or department, and on the other hand, by their capacity to predispose patients for colonization with resistant flora . This is specially important in critical patients who are hospitalized in the Intensive Medicine Department, where the use of antibiotics affects more than 50% of those admitted, and where the appearance of multiresistant pathogens is frequent . The choice of the antibiotics which are used for the empirical and/or focused treatment of the majority of infections, is the basis of the antibiotics policy . It is based on the knowledge of the there essential pillars of the problem: the pathogenic agents which are predominant in each area, the patients' characteristics which favor the appearance of specific micro-organisms, and the antibiotics which can be used for their treatment . In the hospital, the establishment diffusion, and enforcement of these rules, is conducted by a multi-disciplinary committee, in which an intensive care physician specialized in infectious pathology participates, in close collaboration with other specialists (microbiology, pharmacy, infectious diseases), all of whom are committed to the control and correct use of antibiotics.

Enferm Infecc Microbiol Clin, 1997 Oct, 15 Suppl 3, 20 - 6
{Postoperative infections in critically ill patients}; Palomar M et al.; Patients subjected to surgery often develop nosocomial infections, among which the intra-abdominal ones stand out as being a common cause of septicemia, multi-organ failure, and death of the critical patients . Advances have been made in the study of the physiopathology by studying the mediators which are responsible for the systemic inflammatory response, the microbiology (changes in the pathogen type and in the antimicrobial sensitivity), and for the clinical picture (cholecystitis, tertiary peritonitis) . Abdominal ultra-sound and computerized axial tomography have contributed greatly to the diagnosis of these infections . The new treatment techniques are discussed, both of the drainage of the septic focus (percutaneous or surgical), as of the antimicrobial treatment and the supportive measures . The diagnostic and therapeutic advances have modified the prognosis of these patients, although this continues to be poor when there is development of the multi-organ failure syndrome.

Enferm Infecc Microbiol Clin, 1997 Sep, 15 Suppl 1, 45 - 50
{Pharmacoeconomics of meropenem versus imipenem/cilastatin}; Marquina MC et al.; The Pharmacy and Therapeutics Committee of our hospital regulates the use of antimicrobial drugs every year . With the coming into the market of the new antibiotic carbapenem meropenem, comparative meropenem, it was assigned to the Drug Information Center the elaboration of comparative report on the two antibiotics, including as well cost analysis . We have analyzed the activities to be made since an antimicrobial drug is purchased until it is administered . We have only assessed on the direct costs that differ in the two antibiotics that are: the pre-use preparation in the pharmacy service and the preparation and administration in hospital floors . We have classified the direct cost in: goods and services, purchases and supplies costs costs and staff costs . We have calculated the daily cost of both antibiotics in the treatment of serious infections and even in more serious, life threatening infections . On top of that, we have a reviewed the use of imipenem/cilastatin and meropenem in our hospital . The information obtained shows that the saving in serious infections is of 34.6% and of 4.5% in more serious infections with vital compromise . The Pharmacy and Therapeutic Commission taking into account the report elaborated, has considered convenient the choice of meropenem as a representative of carbapenem drugs.

FEBS Lett, 1997 Nov 17, 417(3), 311 - 5
Structural organization of the bovine cathelicidin gene family and identification of a novel member; Scocchi M et al.; Cathelicidins are a group of myeloid antimicrobial peptide precursors found in a variety of mammalian species . Transcripts of this family show a highly conserved 5' region corresponding to the 5' untranslated region, signal peptide and propiece, and diverse 3' regions encoding structurally varied C-terminal sequences that correspond to mature antimicrobial peptides after proteolytic release from the precursors . To establish the size of the bovine gene family encoding these proteins, lambda genomic clones were isolated by screening a bovine library with a probe based on the conserved cDNA region of bovine members . Restriction mapping, hybridization studies and sequence analysis identified 11 distinct genes that based on the intergenic distances of contiguous genes appear to be in close physical proximity . Among these, a novel gene encoding the precursor of a putative alpha-helical antimicrobial peptide was recognized and sequenced . The novel gene appears to be expressed in bovine bone marrow myeloid cells, spleen and testis.

FEBS Lett, 1997 Oct 27, 416(3), 273 - 5
Effect of glucocorticoids on the synthesis of antimicrobial peptides in amphibian skin; Simmaco M et al.; Gene-encoded peptide antibiotics are widespread in insects, plants and vertebrates and confer protection against bacterial and fungal infections . NF-kappaB is an important transcription factor for many immunity-related mammalian proteins and also for insect immune genes . The activity of NF-kappaB is regulated by the interaction with an inhibitor, I kappaB . It was recently demonstrated that glucocorticoids induce the synthesis of I kappaB in human cell lines . So far, all genes for peptide antibiotics have promoter motifs with NF-kappaB binding sites, but its actual function in peptide regulation has been studied only in insects . Here we show that glucocorticoid treatment of the frog Rana esculenta inhibits the transcription of all genes encoding antibacterial peptides by inducing the synthesis of I kappaB alpha . These results suggest that also in vertebrates peptide-mediated innate immunity is controlled by NF-kappaB-regulated transcription.

Arch Pathol Lab Med, 1997 Nov, 121(11), 1168 - 70
Laboratory practices for reporting bacterial susceptibility tests that affect antibiotic therapy; Schifman RB et al.; OBJECTIVE: To evaluate a laboratory-based process for integrating antimicrobial susceptibility, pharmacy, and clinical data with rapid physician notification to improve the care and outcome of patients with bacterial infections . DESIGN: Randomized case control study comparing standard microbiology reporting method with a targeted notification procedure . RESULTS: Of 254 cases studied, a discordance between antimicrobial susceptibility test results and antibiotic therapy was detected in 140 (55%) patients and confirmed after clinical review in 49 (19%) . Appropriate changes in antibiotic therapy were made significantly sooner and in a significantly higher proportion of cases with targeted notification than with standard reporting procedures . CONCLUSIONS: Utilization of antimicrobial susceptibility results is improved by integrating clinical and therapeutic information to identify cases that require physician notification, as measured by the timeliness and appropriateness of antibiotic treatment.

J Antimicrob Chemother, 1997 Oct, 40(4), 595 - 8
Clinical use of rifampicin during routine reporting of rifampicin susceptibilities: a lesson in selective reporting of antimicrobial susceptibility data; Steffee CH et al.; Increased use of rifampicin for in-patients was noted after the laboratory began reporting rifampicin susceptibilities routinely for all Gram-positive bacterial isolates . The appropriateness of rifampicin use was evaluated by chart review for in-patients administered rifampicin during two time periods, before and during routine rifampicin susceptibility reporting, respectively . While rifampicin susceptibility was reported routinely, four patients were subjected to potentially harmful misuse of rifampicin . These findings reconfirm the necessity of interdepartmental consultation and extensive staff education whenever a modification of antimicrobial susceptibility profile reporting is contemplated . Furthermore, they underscore the role of the clinical microbiology laboratory in guiding antimicrobial therapy through limited reporting of susceptibility data.

Biochemistry, 1997 Nov 18, 36(46), 14137 - 45
Structural features of the final intermediate in the biosynthesis of the lantibiotic nisin . Influence of the leader peptide; van den Hooven HW et al.; The antimicrobial membrane-interacting polypeptide nisin is a prominent member of the lantibiotic family, the members of which contain thioether-bridged residues called lanthionines . To gain insight into the complex biosynthesis and the structure/function relationship of lantibiotics, the final intermediate in the biosynthesis of nisin A was studied by nuclear magnetic resonance spectroscopy . In aqueous solution the leader peptide part of this precursor adopts predominantly a random coil structure, as does the synthetic leader peptide itself . The spatial structure of the fully modified nisin part of the precursor is similar to that of nisin in water . The leader peptide part does not interact with the nisin part of the precursor molecule . Thus, these two parts of the precursor do not influence each other's conformation significantly . The conformation of the precursor was also studied while complexed to micelles of dodecylphosphocholine, mimicking the primary target of the antimicrobial activity of nisin, i.e . the cytoplasmic membrane . The location of the molecule relative to the micelles was investigated by using micelle-inserted spin-labeled 5-doxylstearic acid . It was observed that the N-terminal half of the nisin part of the precursor interacts in a different way with micelles than does the corresponding part of mature nisin, whereas no significant differences were found for the C-terminal half of the nisin part . In this model system the leader peptide is in contact with the micelles . It is concluded that the strongly reduced in vivo activity of the precursor molecule relative to that of nisin is not caused by a difference in the spatial structure of nisin and of the corresponding part of precursor nisin in water or by a shielding of the membrane interaction surface of the nisin part of the precursor by the leader peptide . Probably a different interaction of the N-terminal part of the nisin region with membranes contributes to the low activity by preventing productive insertion . The residues of the leader peptide part just next to the nisin part are likely to contribute most to the low activity of the precursor.

J Ethnopharmacol, 1997 Oct, 58(2), 85 - 8
Antimicrobial study of the resinous exudates and of diterpenoids and flavonoids isolated from some Chilean Pseudognaphalium (Asteraceae); Mendoza L et al.; The antimicrobial properties of the resinous exudates from twigs and leaves of four Chilean species of Pseudognaphalium: P . viravira, P . robustum, P . heterotrichium and P . cheiranthifolium were tested against six gram negative bacteria and five gram positive bacteria . The extracts share similar antimicrobial activities against the gram positive bacteria . The antimicrobial activity correlated very well with the presence in the resinous exudates of ent-16-kauren-19-oic acid and to a lesser extent with the presence of ent-9(11),16-kauradien-19-oic . Introduction of an hydrophilic 3 beta-OH drastically reduced the antimicrobial activity of these compound . The activity was not correlated with the flavonoid content of those resinous exudates.

Ann Pharm Fr, 1997, 55(5), 228 - 31
{Ophthalmic preservatives and preparations: reality and perspectives}; Chibret H; Preservatives are used in order to prevent contamination of ophthalmic solutions . Besides their lack of antimicrobial efficacy in certain conditions, they raise number of problems in terms of formulation, stability, interaction with containers . There is also an increasing concern about their deleterious effects in prolonged use on ocular tissues and tear film . Various alternatives have been developed and are analysed in this article.

Ann Pharm Fr, 1997, 55(5), 206 - 11
{Synthesis and structure of substituted arylazo-imidazolidines and arylidenethiazolidines}; Brandao SS et al.; Synthesis and physico-chemical properties of four 3-benzyl or 3-(4-chlorobenzyl)-4-thioxo-5-arylazo-imidazolidin-2-ones, five 3-(4-nitrobenzyl)-5-arylidenethiazolidine-2,4-diones and three 3-(4-phenyl-phenacyl)-4-thioxo-5-arylidenethiazolidin-2-ones have been described . These new products were synthesized by an aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted thioxothiazolidin-2-ones or thiazolidine-2,4-diones . The arylazo-imidazolidine compounds were synthesized by copulation of diazonium ions with imidazolidines . Antimicrobial activity was determined for some compounds.

J R Army Med Corps, 1997 Oct, 143(3), 155 - 9
The chronic prostatitis syndromes; Thin RN; Three chronic prostatitis syndromes are recognised, chronic bacterial prostatitis (CBP), chronic nonbacterial prostatitis (CNBP), and prostatodynia . All may occur in men of military age, and may tax the patience of medical officers and patients whose capacity for full duty will be impaired . Diagnosis depends on identifying micro-organisms in CBP and white cells in CNBP in prostatic secretion (EPS) expressed by prostatic massage . In prostatodynia there are clinical features of prostatitis but no evidence of inflammation . Prostatic massage should be preceded by trans-rectal ultrasound which may show prostatitis and other pathology, and has simplified the investigation of these syndromes . Management includes a high fluid intake, regular bowels with a soft stool, regular prostatic drainage by ejaculation and limited alcohol intake . Antimicrobials are indicated for CBP and probably for CNBP, and need to be continued for at least three months in many cases . Other measures for treating CNBP are less well established . Prostatodynia is an ill defined syndrome which requires careful evaluation and patients may need psychiatric therapy.

Arch Surg, 1997 Dec, 132(12), 1331 - 5; discussion 1335-6
Splenic abscess: another look at an old disease; Phillips GS et al.; OBJECTIVE: To study the changes in the incidence, causes, bacteriologic profile, and management of a splenic abscess . DESIGN: Retrospective case study . SETTING: Tertiary, university referral center . PATIENTS: Thirty-nine patients with a splenic abscess . INTERVENTIONS: None . MAIN OUTCOME MEASURES: Demographics, signs and symptoms, causes, risk factors, diagnostic methods, bacteriologic profile, treatment, and outcome . RESULTS: Patients presented at a mean age of 43 years (range, 2-83 years), after a mean symptomatic period of 16 days, with fever (69%), abdominal pain (56%), nausea and vomiting (38%), and splenomegaly (31%) . The majority of abscesses represented metastatic infection (n=19), and 11 were secondary to immunosuppression . Twelve patients had human immunodeficiency virus disease and 9 used intravenous drugs . In patients who underwent computed tomography, all had abnormal scans (n=33), with a well-defined abscess(es) in 28 . Nine abscesses were polymicrobial; monomicrobial isolates included gram-positive organisms (23%), gram-negative organisms (31%), fungi (23%), and mycobacteria (23%) . Patients presenting before 1989 (1981-1988) (n=15) and those presenting after 1989 (1989-1996) (n=24) differed in risk factors (intravenous drug abuse, 0% vs 47% {P=.02}; hematologic malignancy, 43% vs 9% {P=.04}) and gram-positive isolates (18% vs 64%; P=.06) . Patients underwent splenectomy (n=18), open drainage (n=4), medical therapy (n=10), or percutaneous drainage (n=5) with respective survival rates of 94%, 50%, 70%, and 100% . CONCLUSIONS: In 1996, splenic abscesses are increasingly common . Intravenous drug abuse and human immunodeficiency virus disease are significant risk factors, and the diagnosis should be considered in a patient with fever and abdominal pain who uses intravenous drugs . Antimicrobial agents should be broad since 36% of abscesses were polymicrobial, and should include coverage of gram-positive organisms.

Chem Biol Interact, 1997 Nov 6, 107(1-2), 17 - 30
Primary human hepatocytes as a tool for the evaluation of structure-activity relationship in cytochrome P450 induction potential of xenobiotics: evaluation of rifampin, rifapentine and rifabutin; Li AP et al.; In our laboratory, primary human hepatocytes are being investigated as an in vitro experimental system for the evaluation of pharmacokinetic drug-drug interactions . Our study here represents the first reported study that directly compares the cytochrome P450 isozyme 3A (CYP3A) induction potential of three antimicrobials derived from rifamycin B, namely, rifampin, rifapentine and rifabutin . Two endpoints of CYP3A activity, testosterone 6 beta-hydroxylation and midazolam 1-hydroxylation have been used . Results obtained with hepatocytes from four different human donors show consistently that rifampin and rifapentine are potent inducers of CYP3A, while a significantly lower induction potential is observed for rifabutin . The relative induction potency of the three antimicrobials (rifampin > rifapentine >> rifabutin) is consistent with the available human in vivo data . For CYP1A measured as ethoxyresorufin O-deethylase activity, CYP2C8/9 measured as tolbutamide 4-hydroxylation activity, CYP2D6 measured as dextromethorphan O-demethylation, and AZT glucuronidation, there is either no effect or, where induction is found to be statistically significant in these other endpoints, the maximum induction values are consistently < 100% of the control . Our results suggest that CYP3A is the major CYP induced by these rifamycin B derivatives . These studies illustrate the application of human hepatocytes in the evaluation of the structure-activity relationships in CYP induction for this class of chemicals and as an in vitro screen for drug-drug interaction potential via CYP induction.

Clin Infect Dis, 1997 Nov, 25(5), 1038 - 43
Value of serology as a noninvasive method for evaluating the efficacy of treatment of Helicobacter pylori infection; Perez-Perez GI et al.; The systemic humoral response to Helicobacter pylori was studied in 86 infected adult patients before antimicrobial therapy and at intervals following therapy . Endoscopy with collection of biopsy specimens was performed immediately before treatment; a 13C-labeled urea breath test was performed, and blood specimens were collected before treatment and at 1, 3, 6, 9, and 12 months after treatment . Serum samples from three patient groups (eradication success {n = 50}, eradication failure {n = 16}, and no treatment {n = 20}) were assayed for IgA and IgG antibodies to H . pylori by enzyme-linked immunosorbent assay . Levels of antibody to H . pylori before treatment were similar in all three groups . As expected, the no treatment and eradication failure groups had no significant changes in antibody levels during the study period . In contrast, for the eradication success group, the specific IgA and IgG antibody levels decreased progressively and significantly . We conclude that serology is a potentially useful way to monitor the success of treatment of H . pylori infection without using invasive or more expensive methods.

Clin Infect Dis, 1997 Nov, 25(5), 1027 - 31
Rapid recurrence of Helicobacter pylori infection in Peruvian patients after successful eradication . Gastrointestinal Physiology Working Group of the Universidad Peruana Cayetano Heredia and The Johns Hopkins University; Ramirez-Ramos A et al.; Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer . Since gastric cancer is common in Peru, eradication of H . pylori may help to reduce the occurrence of gastric cancer . This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens . The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients . Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H . pylori infection . Of 105 patients with H . pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period . Thirty-five patients from whom H . pylori was eradicated and who were tested for antibodies to H . pylori remained consistently seropositive . Rapid recurrence of H . pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H . pylori in developing countries.

Clin Infect Dis, 1997 Nov, 25(5), 1023 - 6
Antimicrobial treatment of Helicobacter pylori infection; Goodwin CS; Helicobacter pylori is susceptible to many antimicrobials, but clinically only a few are effective . Two antimicrobials with bismuth or ranitidine or a proton pump inhibitor such as omeprazole are required to achieve a cure rate of >90% and to avoid resistance, which occurs when clarithromycin or metronidazole is the single antimicrobial used . Bismuth plus metronidazole and tetracycline is effective but causes more side effects than does treatment with omeprazole, amoxicillin, and clarithromycin; metronidazole can replace clarithromycin . To ensure a high cure rate, treatment is required for 10 days, but 7-day regimens have sometimes been as successful . A course of ranitidine bismuth citrate for 28 days, given with clarithromycin for the first 14 days, cures 80%-85% of patients, but given with amoxicillin it cures only 74% . In developing countries resistance to metronidazole can reach 95% . An inexpensive regimen is bismuth subsalicylate (two tablets) plus furazolidone (100 mg), four times daily for 4 weeks; however, as this yields a cure rate of only 72%, this regimen is not truly cost-effective.

Int J Lepr Other Mycobact Dis, 1997 Sep, 65(3), 345 - 51
Studies on therapeutic activity of benzoxazinorifamycin KRM-1648 in combination with other antimicrobial agents and biological response modifiers interferon-gamma and granulocyte-macrophage colony-stimulating factor against M . leprae infection in athymic nude mice; Maw WW et al.; In the present study, we evaluated the in vivo anti-Mycobacterium leprae activities of KRM-1648 (KRM) given at long intervals in combination with ofloxacin (OFLX), clofazimine (CFZ), and dapsone (DDS) . We also examined the combined effects of two biological response modifiers (BRMs), gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the therapeutic efficacy of KRM . KRM exhibited potent therapeutic efficacy against M . leprae infection in mice even when given at 4-week intervals . KRM displayed increased efficacy in combination with OFLX, CFZ, and DDS (given three or six times per week) when given to mice in the multidrug combination KRM + OFLX + CFZ + DDS . The therapeutic efficacy of KRM given at 4-week intervals was increased by combined use with IFN-gamma but not by GM-CSF . Adoptive transfer of M . leprae antigen-primed lymphocytes of euthymic mice to recipient athymic nude mice with progressive M . leprae infection markedly enhanced host resistance.

Pharmacotherapy, 1997 Nov-Dec, 17(6), 1139 - 47
Sparfloxacin: potential clinical and economic impact in the treatment of respiratory infections; Stein GE et al.; Sparfloxacin is a new oral fluoroquinolone antimicrobial that is highly active against common respiratory pathogens, including multiresistant strains . It is well absorbed and has excellent penetration into upper and lower respiratory tissues . Sparfloxacin is administered once a day and does not interfere with the metabolism of other drugs . The agent is highly effective and safe in the treatment of acute sinusitis, exacerbations of chronic bronchitis, and community-acquired pneumonia . Due to its activity against multidrug-resistant respiratory pathogens, it has the potential to prevent hospitalization as well as decrease parenteral antibiotic therapy . Consequently, it may generate significant pharmacoeconomic benefits to patients and payers of medical care.

Pharmazie, 1997 Nov, 52(11), 844 - 7
Synthesis and antimicrobial testing of 4H-1,2,4-triazole, 1,2,4-triazolo{3,4-b}{1,3,4}thiadiazole and 1,2,4-triazolo{3,4-b}{1,3,4}thiadiazine derivatives of 1H-benzimidazole; Habib NS et al.; Three novel series of benzimidazole derivatives namely 6-substituted 3-{1-(2-alkyl-1 H-benzimidazolyl)methyl}-1,2,4-triazolo{3,4-b}{1,3,4} thiadiazoles 5a-h, 6-substituted 3-{1-(2-alkyl-1H-benzimidazolyl)methyl}-7H-1,2,4 -triazolo{3,4-b}-{1,3,4}thiadiazines 6a-j and 6-thioxo-3-{1-(2-alkyl-1H-benzimidazolyl)methyl}-5,6-dihydro-1,2,4 -triazolo{3,4-b}{1,3,4}-thiadiazoles 7a, b have been prepared by cyclization of the key intermediate 1-{(4-amino-5-mercapto-4 H-1,2,4-triazol-3-yl)methyl}-2-alkyl-1 H-benzimidazoles 3a, b . Furthermore, 1-{(4-arylideneamino-5-mercapto- 4H-1,2,4-triazol-3-yl)-methyl}-2-alkyl- 1 H-benzimidazoles 4a-h have been prepared and some of them were cyclized to 6-substituted 3-{1-(2-alkyl-1H-benzimidazolyl)methyl}-1,2,4-triazolo {3,4-b}{1,3,4}thiadiazoles 5d, h using thionyl chloride . The prepared compounds were tested for antimicrobial activity in vitro; they showed moderate activity.

Helicobacter, 1996 Mar, 1(1), 57 - 61
An increase in Helicobacter pylori strains resistant to metronidazole: a five-year study; Ling TK et al.; BACKGROUND: Metronidazole is one of the most commonly used antimicrobial agents for the treatment of Helicobacter pylori infection . Resistance to metronidazole has been reported worldwide but with a wide range of prevalence . We started using the classical triple therapy (bismuth, tetracycline, and metronidazole) for H . pylori infection in 1991 but recently have experienced a decline in its efficacy in curing the infection . Thus our aim was to investigate in a single center the prevalence of metronidazole-resistant H . pylori over a period of 5 years . MATERIALS AND METHODS: A total of 1,015 different H . pylori strains collected over a period of 5 years were tested for sensitivity against metronidazole, ampicillin, tetracycline, and imipenem . Antibiotic sensitivity was tested by the disk diffusion and agar dilution methods . To elucidate further the possible relationship between these metronidazole-resistant strains, genomic DNA digestion by the Hae III endonuclease and ribotyping were undertaken in a selected group of isolates . RESULTS: In 1991, 29 of 132 (22.0%) tested strains of H . pylori were found to be resistant to metronidazole . Since our initiation at that time of a triple therapy of bismuth, metronidazole, and tetracycline, the prevalence of metronidazole-resistant strains rose rapidly to 73.2% in 1995 . All H . pylori isolates were sensitive to ampicillin, tetracycline, and imipenem . A high degree of genomic heterogeneity was found among these isolates . Thus it is unlikely that the resistant strains of H . pylori were originated from a single clone . CONCLUSIONS: This study shows a rapid increase in metronidazole-resistant H . pylori with the use of an anti-Helicobacter regimen that contains metronidazole . We anticipate that the efficacy of metronidazole-containing anti-Helicobacter regimens will decline with the rapid rise in resistant strains of H . pylori.

Helicobacter, 1996 Mar, 1(1), 43 - 51
Characterization and therapy for experimental infection by Helicobacter mustelae in ferrets; Czinn SJ et al.; BACKGROUND: Numerous clinical trials evaluating the efficacy of various antimicrobial compounds against Helicobacter pylori infection have been performed in humans . A convenient animal model for Helicobacter infection would facilitate the evaluation of novel therapies . These experiments were performed to evaluate the use of ferrets as a model of Helicobacter infection . MATERIALS AND METHODS: Ferrets were infected experimentally with Helicobacter mustelae and subsequently treated with bismuth subsalicylate (BSS) triple therapy (BSS, metronidazole, and amoxicillin), or left untreated . The status of infection and serology was assessed during treatment and for 8 weeks posttreatment . Seven ferrets successfully treated with triple therapy were challenged with H . mustelae and monitored for infection for an additional 5 weeks . RESULTS: Infection of ferrets by H . mustelae was accompanied by gastritis and a specific antibody response . Treatment of H . mustelae-infected ferrets with BSS suppressed bacterial growth in four of nine animals but did not eradicate infection . Triple therapy eradicated infection in all nine ferrets with a reduction in gastric inflammation . No relapse of infection occurred up to 8 weeks posttherapy . Challenge with H . mustelae of ferrets successfully treated with triple therapy resulted in a 100% rate of reinfection . CONCLUSIONS: H . mustelae infection can be eliminated by triple therapy, but this does not result in protective immunity against reinfection by H . mustelae . This model, using a strain of Helicobacter indigenous to the host, may be useful for assessing therapeutic efficacy of novel therapies for the treatment of human infection by H . pylori.

Helicobacter, 1996 Mar, 1(1), 34 - 42
Natural and experimental Helicobacter mustelae reinfection following successful antimicrobial eradication in ferrets; Batchelder M et al.; BACKGROUND: Recrudescence or reinfection may occur after eradication of Helicobacter pylori in humans . MATERIALS AND METHODS: We used the ferret Helicobacter mustelae model to investigate the effect of prior infection and eradication on reinfection by experimental and natural routes . Two groups of ferrets with naturally acquired H . mustelae infection were treated with an eradication protocol using amoxicillin, metronidazole, and bismuth subsalicylate . The ferrets were monitored for recrudescence by repeated cultures of endoscopic gastric mucosal biopsies . The ferrets were challenged at 17 months (group I) and 6 months (group II) after eradication with a strain of H . mustelae having a distinctive restriction endonuclease analysis pattern . The eradication protocol was repeated to eliminate the infection produced by experimental challenge . The ferrets were then cohoused intermittently with naturally infected ferrets . RESULTS: The original H . mustelae infection was successfully eliminated by the eradication protocol . No recrudescence was observed in group I for 12 months nor for 3 months in group II after eradication . All ferrets became persistently reinfected with the challenge strain . The infection from the challenge strain was eradicated successfully . No ferrets in group I and all ferrets in group II became infected through cohousing . CONCLUSIONS: These results suggest that though prior infection with H . mustelae may confer some protection against reinfection, such protection is not universal in all circumstances; that susceptibility to reinfection by contact with infected animals varies between individuals; and that age may be a factor in this individual variability . These results are applicable to studies of reinfection after eradication of H . pylori in humans.

Helicobacter, 1996 Mar, 1(1), 6 - 19
Treatment of Helicobacter pylori infection: a review of the world literature; van der Hulst RW et al.; BACKGROUND: None of the currently used anti-Helicobacter pylori drug regimens cures the infection 100%, and cure results still vary considerably . The present article reviews the effectiveness of currently used antimicrobial regimens, aimed to cure H . pylori infection . METHODS: Data collection started from the beginning of the anti-H . pylori-therapy era until May 1995 . No attempt at formal metanalysis has been made, because many studies have been published only in abstract form . Attempts were made to exclude duplicates of studies by comparison to previously reported ones; the authors of suspected duplicates were contacted . After amalgamation of the number of included patients and the number of successfully treated patients, the mean values of eradication rates and the 95% confidence intervals were calculated . RESULTS: A total of 237 treatment arms were analyzed . Bismuth triple therapy continues to reach high eradication rates worldwide (78-89%) . Side effects leading to diminished patient compliance and the marked decline of eradication efficacy in cases of metronidazole resistance are considered to be the major drawbacks of this therapy . Proton pump inhibitor (PPI) dual therapy is better tolerated with fewer side effects than is bismuth triple therapy . The mean eradication rates vary from 55 to 75%, and the extremes lie between 24 and 93% . PPI triple therapies have been shown to be very effective against H . pylori (eradication rates, 80-89%) . Quadruple therapy leads to a mean eradication rate of 96% . CONCLUSION: Based on efficacy, PPI triple or bismuth triple therapy are recommended as first-line treatment for H . pylori infection . Quadruple therapy could serve as second-line treatment for eradication of initial failures and in case of metronidazole resistance.

Helicobacter, 1996 Sep, 1(3), 138 - 44
Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study; Lind T et al.; BACKGROUND: Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials . The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established . MATERIALS AND METHODS: We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom . Patients (n = 787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following antimicrobials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M) . Eradication of H . pylori was evaluated by 13C-UBT, performed before and 4 weeks after treatment cessation . RESULTS: The eradication rates for the all-patients-treated analysis were 96%, OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP . OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90% . All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events . CONCLUSIONS: Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance . The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.

Helicobacter, 1996 Jun, 1(2), 88 - 91
Is antrum or corpus the best site for culture of Helicobacter pylori?
Yousfi MM, Reddy R, Osato MS, Graham DY.
BACKGROUND: Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected . The aim of this study was to determine whether the yield of H . pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy . METHODS: Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured . H . pylori status was determined by histological assessment using the Genta stain . RESULTS: Fifty-two patients with documented H . pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed . In 47 patients (90%), both antral and corpus culture specimens were positive . In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures . The overall sensitivity of culture in detecting H . pylori infection was 95% (95% confidence interval = 89-98%) and was not significantly different for the antrum or corpus, either before or after therapy . CONCLUSION: Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.

Helicobacter, 1996 Dec, 1(4), 197 - 206
Immunohistochemical detection of Helicobacter pylori in the surface mucous gel layer and its clinicopathological significance; Shimizu T et al.; BACKGROUND: Attempts have been made to develop an accurate method for detecting Helicobacter pylori in histological sections . MATERIALS AND METHODS: Biopsy specimens were obtained from the stomachs of 167 patients with gastric ulcer (33), duodenal ulcer (52), gastroduodenal ulcer (15), chronic gastritis (45), and normal mucosa (22) before antimicrobial treatment and from 108 of these patients after treatment . Biopsy specimens were (1) cultured, (2) fixed in 10% buffered formalin, or (3) fixed in Carnoy's solution . The latter method was employed to preserve the surface mucous gel layer (SMGL) covering gastric surface mucous cells . Histological sections were stained with hematoxylin and eosin (H&E), with immunostaining using a commercially available polyclonal anti-H . pylori antibody . RESULTS: Cultures were positive for H . pylori in 61% of the cases before treatment and in 16% after treatment; by H&E staining using formalin-fixed materials: 70% and 9%; by immunostaining using formalin-fixed materials: 78% and 21%; and by immunostaining using Carnoy-fixed materials: 85% and 41% of biopsy specimens, respectively . The difference in detection rates between materials fixed in formalin and those in Carnoy's solution was due to the detection of H . pylori in the SMGL by the latter, especially after antimicrobial treatment . CONCLUSIONS: Immunostaining for H . pylori using materials fixed in Carnoy's solution revealed H . pylori in the SMGL as well as on the surface mucous cells and in the gastric pits and permitted the optimal detection of H . pylori in tissue sections.

Biochem Biophys Res Commun, 1997 Nov 26, 240(3), 657 - 63
Presence of antibacterial peptides on the laid egg chorion of the medfly Ceratitis capitata; Marchini D et al.; Female reproductive accessory glands of the medfly Ceratitis capitata produce a secretion with antibacterial activity mainly ascribed to ceratotoxin peptides . To study whether the secretion from the accessory glands of the female protects the eggs and early larva from microbes, we examined whether ceratotoxins and other accessory gland components could be found on the egg surface . This was found to be the case; a water-soluble material with the same protein and antibacterial pattern as that of the accessory gland secretion was recovered from the laid egg surface and was observed as electrondense, clustered droplets over the outer exochorion . Such material showed the same electrophoretic pattern in both mated and virgin females . These findings indicate that the accessory gland secretion is spread, at oviposition, onto the eggs producing an antibacterial coating, irrespective of fertilization . This is the first report of antimicrobial components recovered from a material layered on insect laid eggs.

Clin Perinatol, 1997 Dec, 24(4), 787 - 806
Infections of the central nervous system in the newborn; Bale JF Jr et al.; Safe, effective vaccines and potent antimicrobial agents have diminished substantially the morbidity and mortality associated with neonatal infections of the central nervous system (CNS), and new molecular methods, such as the polymerase chain reaction, enable clinicians to detect micro-organisms rapidly . Despite these advances, CNS infections remain an important cause of death and neurodevelopmental sequelae . This article summarizes current concepts regarding infections of the developing CNS.

J Altern Complement Med, 1996 Summer, 2(2), 271 - 7
Beneficial effect of Aloe on wound healing in an excisional wound model; Heggers JP et al.; Recent evidence from in vitro and in vivo experiments suggests that topical antimicrobials may be toxic to fibroblasts and keratinocytes and retard wound healing . The purpose of this study was to determine the effects of Aloe, a potential wound-healing agent, on wound contraction in excisional wounds treated with topical antimicrobials . Sprague-Dawley rats were prepared with four 1.5 cm2 dorsal defects through the skin and panniculus . The animals were divided into five groups (n = 10 per group): (1) Aloe, (2) NaOCl solution (0.025%), (3) mafenide acetate, (4) mafenide acetate + Aloe, and (5) control . Wounds were treated topically for 14 days 3 times a day . Serial standard photographs and serial wound planimetry were performed weekly . Following healing, the breaking strength of each resultant scar was determined using an Instron tensiometer . Kruskal-Wallis, ANOVA, and multiple comparison methods were used for data analysis . Aloe and NaOCl solution significantly accelerated wound contraction (p < 0.05) . In the mafenide acetate + Aloe group, contraction was similar to the control, whereas the mafenide acetate alone retarded wound healing . The addition of Aloe in combination and alone in wounds increased the breaking energy when compared to controls (p < 0.05) . Aloe appears to expedite wound contraction and neutralize the wound retardant effect seen with the topical mafenide acetate alone . This effect appears to be due to an increased collagen activity, which is enhanced by a lectin, consequently improving the collagen matrix and enhancing the breaking strength.

Gastroenterology, 1997 Dec, 113(6 Suppl), S149 - 53
What is the role for vaccination in Helicobacter pylori?
Czinn SJ.
Helicobacter pylori has been implicated in the etiology of peptic ulcer disease, chronic gastritis, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma . Although significant progress has been made in treating this infection with combinations of either antimicrobial agents or antimicrobial agents plus proton pump inhibitors, these antimicrobial-based treatments continue to be suboptimal . Over the past few years it has become increasingly recognized that direct mucosal immunization can induce protection from infection at mucosal surfaces . Therefore, prevention of H . pylori infection by oral immunization is an alternative approach for the control of H . pylori disease . Using the Helicobacter felis mouse model or H . pylori mouse model, both prophylactic and therapeutic oral immunizations have been shown to be effective against H . pylori . In addition, several H . pylori proteins have been identified as potential candidate vaccines, and a phase 1 clinical trial has been completed that demonstrates the safety and tolerability of urease as a vaccine antigen . Such antigens in combination with a safe mucosal adjuvant could be used in the form of an oral vaccine administered during childhood before exposure to H . pylori to prevent infection . In addition, therapeutic immunization alone or as an adjunct to antimicrobial therapy may be capable of achieving a cure rate approaching 100%.

Gastroenterology, 1997 Dec, 113(6 Suppl), S131 - 48
What other regimens are under investigation to treat Helicobacter pylori infection?
Unge P.
The most common infection in the world, Helicobacter pylori infection, is very specific, and present experience in treating infectious diseases is not applicable in general for this infection . Animal models (e.g., mouse and ferret) are thus far inadequate as reliable screening models . Old-fashioned trial-and-error treatment of infected humans is still the screening model and the gold standard in the evaluation of regimens aimed at eradication of H . pylori . A variety of studies on treatment of H . pylori infection have been performed with varying results . This pooled analysis of the following therapeutic combinations: proton pump inhibitor (PPI) plus two antibiotics or antimicrobials, quadruple therapies, and nonantibiotic regimens is an attempt to make a fair comparison of tested therapeutic strategies aimed at eradicating H . pylori . Data from treatment groups including specified drug combinations are pooled, regardless of dose or duration . Search methods are: MEDLINE 1984-1996, Digestive Disease Week 1988-1996, United European Gastroenterology Week 1992-1996, European Helicobacter pylori Study Group 1988-1996, Asia Pacific Congress 1996, H . pylori International Workshop Hong Kong 1996, and miscellaneous . Eradication rates (efficacy) are presented as intention-to-treat data (i.e., worst-case analysis) . Separate subanalyses with regard to study quality, dose, and duration are performed for some groups . A general cost-efficacy analysis is performed based on pooled efficacy data . Convenience data are presented as total number of tablets, total number of intake occasions, and duration of therapy . Drugs evaluated in the analysis are bismuthdicitrate, tetracycline, amoxicillin, nitroimidazoles, macrolides, H2-receptor antagonists, PPIs, sucralfate, and sofalcone . The most effective and convenient drug combinations are the PPI-based triple therapies . No significant difference was observed between the three PPIs . The cure rate did not improve after addition of bismuth . Cost-effectiveness is closely associated with efficacy.

Gastroenterology, 1997 Dec, 113(6 Suppl), S126 - 30
Current FDA-approved treatments for Helicobacter pylori and the FDA approval process; Hopkins RJ; U.S . Food and Drug Administration (FDA) approval of new drugs expands treatment options and serves as a "safety net" of well-documented efficacy and safety . The information provided in the package insert facilitates physician education and provides some assurance that marketing information is accurate . As of February 1997, three Helicobacter pylori regimes have been FDA-approved for eradication of H . pylori in infected patients with active duodenal ulcers . Regimen 1, omeprazole + clarithromycin (O/C), was supported by two multicenter, controlled studies with a 6-month follow-up . Eradication rates were 74% (n = 53; 95% confidence interval {CI}, 62-85) and 64% (n = 61; 95% CI, 52-76) . Twenty-five of 26 patients with failed eradication therapy who were taking O/C with clarithromycin-susceptible strains before treatment and who had pretreatment and posttreatment susceptibility tests performed developed clarithromycin resistance after treatment . Regimen 2, ranitidine-bismuth-citrate + clarithromycin, was supported by two multicenter, placebo-controlled studies with a 6-month follow-up . Eradication rates were 84% (n = 19; 95% CI, 60-96) and 73% (n = 22; 95% CI, 50-88) . Insufficient pretreatment and posttreatment susceptibility data were collected to assess antimicrobial resistance . Regimen 3, bismuth subsalicylate + metronidazole + tetracycline + an H2-receptor antagonist, was supported by two pivotal literature-based studies . Eradication rates in patients with duodenal ulcer were 82% (n = 51; 95% CI, 70-92) and 77% (n = 39; 95% CI, 61-89), respectively . When extrapolating the results of these three FDA-approved regimens to the clinical setting, particular aspects of the clinical trial should be kept in mind . These include the type of controls, primary end points used, population studied, and number and type of dropouts.

Gastroenterology, 1997 Dec, 113(6 Suppl), S93 - 8
How should Helicobacter pylori infection be diagnosed?
Megraud F.
The ideal approach for the initial diagnosis of Helicobacter pylori infection is to perform an endoscopy to obtain biopsy specimens for histology and culture . Histology allows classification of any gastritis lesions present and may have prognostic value, and culture enables susceptibility testing of antimicrobial agents to direct proper treatment . Biopsy specimens must also be taken from the corpus if the patient was pretreated with proton pump inhibitors . The cost of these tests and the delay in receiving results limits their use in clinical practice . Therefore, the urease test, a quick and inexpensive test, is used to detect the presence of H . pylori and constitutes the basic invasive test for H . pylori . A new urease test based on a strip instead of an agar disk may be the test of choice in the future, because of its increased sensitivity and 2-hour delay (instead of 24 hours) in obtaining the result . In some countries, because of the cost, endoscopy will be used in selected patients only, either because of alarm symptoms or age > 45 years, which is considered a threshold for gastric cancer risk . In other patients, the noninvasive tests will be used . The cost of serology makes it more attractive compared with the urea breath test . Currently, there are accurate enzyme-linked immunosorbent assay tests that can be performed in any laboratory and that provide precise and quick diagnoses . In the event of a doubtful result, an immunoblot can be performed, as is the case for other infections . Patient follow-up after treatment provides a different situation because bacterial load is usually lower . A noninvasive test should be performed, and only the urea breath test can be used within the timing originally proposed to test eradication efficacy (i.e., 4-6 weeks after treatment) . If the result is positive, susceptibility testing is required before administering a second course of treatment . The increasing use of antimicrobial agents to treat H . pylori is likely to result in antimicrobial resistance, requiring that bacteriologic surveillance programs be implemented . There are numerous research projects ongoing in this area, and one can expect that improved methods, such as colorimetric polymerase chain reaction (PCR) and improved antibody tests, will also be used in the future.

Bioessays, 1997 Nov, 19(11), 1019 - 26
Antimicrobial peptide defense in Drosophila; Meister M et al.; Drosophila responds to a septic injury by the rapid synthesis of antimicrobial peptides . These molecules are predominantly produced by the fat body, a functional equivalent of mammalian liver, and are secreted into the hemolymph where their concentrations can reach up to 100 microM . Six distinct antibacterial peptides (plus isoforms) and one antifungal peptide have been characterized in Drosophila and their genes cloned . The induction of the gene encoding the antifungal peptide relies on the spatzle/Toll/cactus gene cassette, which is involved in the control of dorsoventral patterning in the embryo, and shows interesting structural and functional similarities with cytokine-induced activation of NF-kappa B in mammalian cells . An additional pathway, dependent on the as yet unidentified imd (for immune-deficiency) gene, is required for the full induction of the antibacterial peptide genes . Mutants deficient for the Toll and imd pathways exhibit a severely reduced survival to fungal and bacterial infections, respectively . Recent data on the molecular mechanisms underlying recognition of non-self are also discussed in this review.

J Nat Prod, 1997 Nov, 60(11), 1115 - 20
Sesquiterpenoids of the drimane class from a sponge of the genus Dysidea; Paul VJ et al.; Ten sesquiterpenoids, including seven new ones, have been isolated from an undescribed sponge of the genus Dysidea . Compounds 1-8 are sesquiterpenoids of the drimane class, while 9 and 10 are 12-norsesquiterpenoids of the same structural class . The structures of novel compounds have been determined by combined spectroscopic methods . These compounds exhibited moderate antimicrobial and enzyme inhibitory (Na+/K(+)-ATPase and PLA2) activities.

Dermatol Nurs, 1997 Oct, 9(5), 339 - 44
Azelaic acid 20% cream (AZELEX) and the medical management of acne vulgaris; Gibson JR; Azelaic acid 20% cream (AZELEX) is a novel anti-acne agent with antimicrobial activity and keratinization-normalizing properties . In acne it is broadly comparable in efficacy to 0.05% tretinoin, 5% benzoyl peroxide, and 2% erythromycin, but is less irritating than tretinoin and benzoyl peroxide.

Crit Care Nurs Q, 1997 Nov, 20(3), 89 - 102
Antibiotic classification: implications for drug selection; Cuddy PG; This article presents a useful antibiotic classification model for the busy clinician who must select agents for patients in the critical care setting . The model organizes antibiotics based on their mechanism of action, ie, cell-wall inhibitors, nucleic acid inhibitors, and protein-synthesis inhibitors; clinicians are encouraged to further segregate agents within the broader categories by generation . An overview of the antimicrobial spectrum for each class is presented, and important differences within individual classes are highlighted . The most common indications for each antibiotic class are reviewed, and key pharmacokinetic characteristics that help distinguish one drug from another are outlined.

Crit Care Nurs Q, 1997 Nov, 20(3), 60 - 8
Antibiotics: why they fail in patients who are critically ill; Bamberger DM; Most of the failures of antimicrobial therapy can be related to advanced infections in patients with serious comorbid processes or altered immunity . However, some of the failures are related to the type of antimicrobial therapy used, the length of therapy, the pharmacokinetic or pharmacodynamic properties of the antimicrobial agent, the development of antimicrobial resistance, microbial factors that influence antimicrobial efficacy, and the site and type of infection . This report will review the common mechanisms by which antimicrobials fail.

Eur Spine J, 1997, 6(5), 327 - 9
Aseptic spondylitis as the initial manifestation of the SAPHO syndrome; Kotilainen P et al.; We describe the case of a 61-year-old female patient who presented with spondylitis of the lumbar spine . Although the microbiological cultures of the bone biopsy specimens obtained during laminotomy remained negative, the patient was treated with broad-spectrum antimicrobials for 2 months . Eight months later she started to suffer from pain and tenderness in her sternum and the medial portion of her left clavicle . The findings of computed tomography and gallium-labelled isotope scan were indicative of sternoclavicular arthritis . Again, all surgically obtained biopsy specimens yielded negative results in microbiological studies . The diagnosis of the SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteomyelitis) syndrome was then made based on the clinical presentation with recurrent sterile osteitis in two characteristic locations, and the patient was started on immunosuppressive therapy . This case is a reminder that SAPHO may sometimes occur without any skin manifestations . Since this type of patient may be admitted to an orthopedic ward, it is important that orthopedic surgeons are familiar with the syndrome.

Pharmacoeconomics, 1998 Jan, 13(1 Pt 1), 35 - 49
Economic aspects of antibacterial adverse effects; Beringer PM et al.; The economic impact of adverse effects is often understated . Increased hospitalisations attributed to adverse drug reactions alone account for billions of dollars each year within the US healthcare system . Although most classes of antibacterials are well tolerated, severe reactions do occur and can add significantly to the cost of care . Among hospitalised patients, antibacterial adverse effects account for nearly 25% of adverse drug reactions . Published pharmacoeconomic data on direct and indirect costs of antibacterial adverse effects are lacking . The importance of determining the most cost-effective treatment regimen is becoming more apparent due to limited resources available within the healthcare system . When considering the cost of new antibacterials, a simple comparison of acquisition costs may not accurately reflect the true costs of treatment . A drug with a lower acquisition cost may be more toxic and/or less effective, resulting in higher complication rates and/or treatment failures, thus leading to a higher overall treatment cost . In addition, nephrotoxic agents such as aminoglycosides and vancomycin often require close monitoring of serum drug concentrations and creatinine levels, which also contributes to the total cost of therapy . Indirect costs as a result of reduced quality of life or loss of productivity are certainly not reflected in the acquisition costs of antimicrobials . Institutions must evaluate a drug's potential for causing and adverse event, among various other factors, when considering drugs for inclusion on their formularies . Drugs with good safety profiles may minimise hospitalisation or facilitate early discharge . Thus, the adverse effect profile of an antimicrobial agent can contribute significantly to its overall direct costs, primarily as a result of higher monitoring costs and additional days of hospitalisation . For example, in the US, the cost associated with adverse effects, such as nephrotoxicity, observed with aminoglycosides and vancomycin, may add approximately $US2500 per patient with nephrotoxicity (1990 values) . Indirect costs can also be substantial as a result of reduced productivity . Many adverse effects of antibacterial agents are predictable and may be minimised with appropriate monitoring and care . This article reviews the pharmacoeconomic aspects of adverse effects associated with some of the more important antibacterial classes such as the beta-lactams, aminoglycosides, vancomycin, macrolides and fluoroquinolones.

Endocrinology, 1997 Dec, 138(12), 5597 - 604
Expression of adrenomedullin and its receptor in normal and malignant human skin: a potential pluripotent role in the integument; Martinez A et al.; Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including growth regulation and antimicrobial activity . We have determined by immunohistochemistry and in situ hybridization that AM and its receptor are present in all the epithelial cells of the normal skin, including keratinocytes of the epidermis and hair follicles, as well as cells of the glands and secretory ducts . We also have detected AM in the sweat, by RIA . In addition, AM and its receptor were found in skin tumors of different histologies . The presence of AM and its receptor in normal and neoplastic skin was confirmed by RT-PCR and Western blot analysis performed on cell extracts from human skin cell lines . Radiolabeled AM bound to specific sites in cultured cells with a Kd of 9 nM . This binding was blocked by the addition of cold AM but not by related peptides such as AM 22-52, pro-AM 20 N-terminal peptide, calcitonin gene-related peptide, calcitonin gene-related peptide 8-37, or amylin . Finally, exposure to synthetic AM resulted in an increase of thymidine intake by skin cells . These results implicate AM as a potential player in skin defense against infectious microorganisms and as a possible autocrine growth factor in normal skin physiology and tumor development.

J Acquir Immune Defic Syndr Hum Retrovirol, 1997, 16 Suppl 1, S14 - 22
Prevention of opportunistic infections in the era of improved antiretroviral therapy; Chaisson RE et al.; Patients with advanced human immunodeficiency virus (HIV) infection who are severely immunosuppressed develop a variety of opportunistic infections that have a significant impact on their well-being, quality of life, health-care costs, and survival . The risk for development of opportunistic infections depends on exposure to potential pathogens, the virulence of the pathogens, the degree of host immunity, and the use of antimicrobial prophylaxis . Many studies have confirmed the benefits of prophylaxis in severely immunosuppressed patients . Factors that affect the use of prophylaxis for prevention of opportunistic infections in HIV-infected patients include the prevalence and potential severity of the disease, ease of treatment if infection occurs, the cost-effectiveness of the prophylactic regimen, and the potential for increased survival, drug toxicity, drug interactions, and emergence of resistance with the regimen . The United States Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) have established disease-specific recommendations for use of prophylaxis for opportunistic infections in HIV-infected patients . These guidelines identify regimens that are strongly recommended as standards of care, regimens that should be seriously considered in selected patients, and regimens that are not routinely indicated but may be considered in selected patients . Although further study is needed, advances in antiretroviral therapy may have an important impact on the recommendations for prophylaxis and may eventually allow discontinuation of these regimens in patients who regain functional immunity.

J Exp Clin Cancer Res, 1997 Sep, 16(3), 321 - 4
Triple combination antimicrobial regimen in the treatment of infections of neutropenic cancer patients; Casali A et al.; Twenty-six cancer patients (pts) with chemotherapy-related neutropenic fever were treated with vancomycin 30 mg/m2/day i.v . every 12 hrs, imipenem 1500 mg/day i.v . every 8 hrs, and pefloxacin 800 mg/day i.v . every 12 hrs . Twelve fevers of unknown origin (FUO), 10 gram-positive, 3 gram-negative and 1 mycoplasma were also treated . Globally, cure was observed in 22 pts (84%) and failure in 4 pts (16%); in gram-positive infections alone, cure was observed in 10 pts (80%) and failure in 4 pts (20%) . Defervescence was obtained within 3 days in 77% pts . No relevant side effects were observed.

Zhonghua Liu Xing Bing Xue Za Zhi, 1996 Oct, 17(5), 289 - 91
{Surveillance on Vi-II phage typing and antimicrobial susceptibilities of S . typhi strains in Beijing City}; Zhang JX et al.; From 1973 to 1989, 961 strains of S . typhi collected in Beijing City were tested for their Vi-II phage typing and antimicrobial susceptibilities . The results of phage typing showed that 38 types were found with a high prevalence of types A, D2, E1, K1, D5, D1, O, D4, and L1 . The results of antimicrobial susceptibilities showed that all of the 168 local strains were highly susceptible to chloramphenicol, similar to the 96 phage typing standard strains.

Antimicrob Agents Chemother, 1997 Nov, 41(11), 2394 - 8
Novel antimicrobial peptides derived from human immunodeficiency virus type 1 and other lentivirus transmembrane proteins; Tencza SB et al.; We have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the natural antimicrobial peptides cecropins and magainins in overall structure but bear no sequence homology to them or other members of their class . We describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides (LLPs) . The results of this study demonstrate that they are potent and selective antibacterial peptides: the prototype sequence, LLP1, is bactericidal to both gram-positive and gram-negative organisms at micromolar concentrations in 10 mM phosphate buffer . Furthermore, LLP1 kills bacteria quite rapidly, causing a 1,000-fold reduction in viable organisms within 50 s . Peptides corresponding to sequences from three lentivirus envelope proteins were synthesized and characterized . Several of these peptides are selective, killing bacteria at concentrations 50- to 100-fold lower than those required to lyse erythrocytes . Development of antimicrobial agents based on these peptides may lead to improved therapeutics for the management of a variety of infectious diseases.

Biochim Biophys Acta, 1997 Oct 23, 1329(2), 285 - 90
Interaction of a synthetic peptide based on the neutrophil-derived antimicrobial protein CAP37 with dipalmitoyl-phosphatidylcholine membranes; Polikandritou Lambros M et al.; CAP37, a cationic antimicrobial protein of Mr 37 kDa is constitutively expressed in human neutrophils . A synthetic peptide, CAP37 P20-44, corresponding to amino acid residues 20 through 44 of the native CAP37 molecule has been shown to mimic the antimicrobial activity of the native protein . An analog of peptide CAP37 P20-44 was synthesized in which the cysteine residues at positions 26 and 42 were replaced with serine residues (CAP37 P20-44Ser) . This resulted in a peptide that no longer exhibited bactericidal activity . The effect of different concentrations of the active CAP37 peptide, CAP37 P20-44, and its inactive analog, CAP37 P20-44Ser, on artificial lipid membranes composed of dipalmitoyl phosphatidylcholine (DPPC) was studied using small-angle X-ray scattering and differential scanning calorimetry . The results indicated that CAP37 P20-44 perturbs the periodicity of the lamellar structure as shown by small angle X-ray diffraction, while the effect of the inactive peptide is not as strong . Differential scanning calorimetry further confirms that CAP37 P20-44 interacts with lipid membranes as indicated by increased width of the transition and decreased peak height . Moreover, it completely abolishes the pretransition temperature of the DPPC membranes . The effect of the inactive peptide, CAP37 P20-44Ser on the thermotropic properties of DPPC was small . These studies suggest that CAP37 perturbs the lamellar structure of lipid bilayers and further suggests that the antibiotic action of the molecule may be through its interactions with the lipid components of the Gram negative bacterial membrane.

Antimicrob Agents Chemother, 1997 Nov, 41(11), 2570 - 2
Structure-activity studies of quinolone-penems in genetically defined strains of Escherichia coli; Ehrhardt AF et al.; Quinolonyl-beta-lactam antimicrobial agents (QLAs) contain quinolones chemically linked to beta-lactams, although the impact of linkage is poorly understood . Genetically defined Escherichia coli strains were used to determine structure-activity characteristics of three quinolone-penem QLAs . Results suggest that the leaving group resulting from beta-lactam hydrolysis may not be free quinolone.

Antimicrob Agents Chemother, 1997 Nov, 41(11), 2448 - 55
Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats; Kordick DL et al.; Enrofloxacin and doxycycline are antimicrobial agents used to treat bacterial diseases of cats . In vitro susceptibility data indicate that either drug should be effective against Bartonella species . In vivo efficacies of these drugs for eradication of chronic Bartonella henselae or Bartonella clarridgeiae infections were examined in 18 experimentally infected cats and 25 naturally exposed cats treated with enrofloxacin (22.7 mg given orally {PO} every 12 h {q12h} {14 days, n = 10; 28 days, n = 13}) or with doxycycline (25 mg PO q12h {14 days, n = 9; 28 days, n = 8}) or not treated (n = 3) . Plasma drug concentrations were determined in experimental cats by high-performance liquid chromatography . Only 23 of 43 cats enrolled ultimately met inclusion criteria . Bacteremia was eliminated for 12 to 25 weeks posttreatment in four of seven cats receiving 14 days of enrofloxacin, five of seven cats receiving 28 days of enrofloxacin, one of six cats receiving 14 days of doxycycline, and one of two cats receiving 28 days of doxycycline . Defining a negative result by blood culture as treatment success may be erroneous; these results may reflect the insensitivity of blood culture or the relapsing nature of Bartonella bacteremia . Our results suggest that MICs obtained with axenic media do not predict antimicrobial activity against intracellular Bartonella, that a long treatment course is required to eliminate infection, and that duration of therapy correlates with pretreatment bacterial load . Given current concern about the development of antimicrobial resistance, we would reserve recommendation for treatment to cats owned by an immunocompromised individual or as an alternative to euthanasia of a pet.

Antimicrob Agents Chemother, 1997 Nov, 41(11), 2389 - 93
Characterization of fluoroquinolone-induced Achilles tendon toxicity in rats: comparison of toxicities of 10 fluoroquinolones and effects of anti-inflammatory compounds; Kashida Y et al.; Fluoroquinolone antibacterial agents have been reported to induce tendon lesions in juvenile rats . In the present study, we characterized fluoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these antimicrobial agents, pefloxacin, to induce tendon lesions when coadministered with one of nine anti-inflammatory compounds . Among the 10 fluoroquinolones tested, fleroxacin and pefloxacin were the most toxic, inducing lesions at a dose of 100 mg/kg of body weight or more, while lomefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin induced lesions at 300 mg/kg or more and 900 mg/kg, respectively . In contrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect even at the high dose of 900 mg/kg . The severity of the Achilles tendon lesions appeared to correlate with the structure of the substituent at the seventh position . Furthermore, pefloxacin-induced tendon lesions were inhibited by coadministration with dexamethasone and N-nitro-L-arginine methyl ester . Phenidone (1-phenyl-3-pyrazolidinone) and 2-(12-hydroxydodeca-5,10-diynyl)3,5,6-trimethyl-1,4-benzoqui none (AA861) also decreased the incidence of tendon lesions . In contrast, catalase, dimethyl sulfoxide, indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions . These results suggest that nitric oxide and 5-lipoxigenase products partly mediate fluoroquinolone-induced tendon lesions.

Curr Opin Hematol, 1994 Jan, 1(1), 78 - 84
Leukocyte-derived antimicrobial proteins; Weiss J; Survival in environments teeming with microbes depends on efficient mechanisms of host defense . Antimicrobial peptides and polypeptides in granules of leukocytes (eg, neutrophils) provide an important arm of first-line defense against invading microorganisms . Recent studies have broadened the scope and settings in which these proteins may function and, in at least one case, are leading to the development of a recombinant product that may provide a novel therapy for bacterial diseases when endogenous defenses are limiting.

Bioorg Med Chem, 1997 Oct, 5(10), 1959 - 68
Preparation, antimicrobial evaluation, and mutagenicity of {2-hydroxyaryl}-{1-methyl-5-nitro-1H-2-imidazolyl}methanols , {5-tert-butyl-2-methylaminophenyl}-{1-methyl-5-nitro-1H-2-imidazo lyl}me thanol, and {2-hydroxyaryl}-{1-methyl-5-nitro-1H-2-imidazolyl} ketones; Arredondo Y et al.; Efficient preparations of the titled compounds are described, their antimicrobial activity and mutagenic properties being evaluated . Some of the studied compounds are nonmutagenic and present a MIC as low as some of the usual standards in the field.

Biol Reprod, 1997 Nov, 57(5), 1115 - 22
Antimicrobial protection of the mouse testis: synthesis of defensins of the cryptdin family; Grandjean V et al.; We report the synthesis by mouse testicular cells of antibiotic peptides related to the defensins secreted by the Paneth cells of the intestinal epithelium . A Sertoli cell-derived line (15P-1), Sertoli cells in primary cultures, and explanted testicular tissue in culture medium were observed to release protease-sensitive material with a broad-spectrum antibacterial activity . The activity of 15P-1 culture medium was increased 10- to 50-fold in the presence of fractions enriched in round spermatids and of nerve growth factor . Two series of results suggest that this activity may correspond to the release by testicular cells of defensin peptides, and specifically, of peptides of the cryptdin family first identified in the Paneth cells of intestinal crypts . First, a characteristic nucleotide sequence corresponding to the conserved first exon of the mouse cryptdin and cryptdin-related (CRS) genes was evidenced in the RNA of 15P-1 cells and of the testis . Second, immunohistochemical analysis demonstrated the presence of cryptdins of the cryp-1, -2, -3, -6 group in 15P-1 cells, and identified two distinct localizations in the testis . Inside the seminiferous tubule, these cryptdins were found accumulated in Sertoli cells at stages corresponding to the maturation of spermatids . In the interstitial space, Leydig cells also contained immunoreactive cryptdins.

Vet Clin North Am Food Anim Pract, 1997 Nov, 13(3), 549 - 74
Antimicrobial therapy of bovine respiratory disease; Apley M; Our challenge in therapy of BRD is the selection of the appropriate therapy from antimicrobials with long-standing histories and newer compounds . The proliferation of new antimicrobials for BRD makes it difficult to justify the extralabel use of nonlabeled compounds . Evaluation of the BRD case definition and treatment population should be the first steps in selecting therapy and evaluating incidences of poor response.

Vet Clin North Am Equine Pract, 1997 Dec, 13(3), 501 - 17
Antimicrobial therapy for respiratory disease; Bertone JJ; Antimicrobial treatment is an important component of infectious respiratory disease management . However, across all systems in horses there is substantial deficit in definitive information concerning the efficacy of antimicrobials . This disassociation between laboratory data and antimicrobial efficacy and the obstacles to effective antimicrobial treatment should be understood.

Pharmacol Res, 1997 Jul, 36(1), 35 - 9
Effects of the combination antibiotic--EDTA-Tris in the treatment of chronic bovine endometritis caused by antimicrobial-resistant bacteria; Farca AM et al.; The combined effects of the uterine infusion of EDTA-Tris solution and antibiotics have been evaluated in 75 cases of slight, moderate or severe bovine endometritis which did not respond to local routine antimicrobial therapy . Antibiotic-resistant bacteria were isolated from uterine swabs . The cows were divided into three groups on the basis of the severity of endometritis and treated with 100 ml of sterile EDTA-Tris solution (250 mM EDTA and 50 mM tris, pH 8) and the same antibiotic used in the first unsuccessful treatment (oxytetracycline, enrofloxacin, lincomycin-spectinomycin or amikacin) . Control groups consisting of six animals treated with antibiotic alone were used . Clinical evaluations performed 2, 15, 21, 42 and 63 days after treatment revealed good therapeutic results, as 53 cows showed a complete recovery with renormalization of the subsequent oestrus cycle . Artificial insemination was followed by pregnancy in about 90% of treated cows . In control animals the second treatment performed using only the antibiotic gave variable and unsatisfactory results, particularly in animals affected by severe endometritis.

Chest, 1997 Nov 5, 112(5), 1428 - 32
Mycoplasma hominis pneumonia complicating bilateral lung transplantation: case report and review of the literature; Lyon GM et al.; Mycoplasma hominis is a commensal of humans . The organism has been predominantly associated with infections of the genitourinary tract . Extragenital infections have been described in neonates, in women during the postpartum period, and in immunocompromised patients . Pneumonia caused by M . hominis is very rare . This report describes the development of M . hominis pneumonia in a lung transplantation recipient and underscores the difficulty in establishing the correct diagnosis and the need for early and aggressive treatment with appropriate antimicrobial agents to insure a good outcome.

Chest, 1997 Nov 5, 112(5), 1214 - 20
Inflammatory mediators in BAL fluid as markers of evolving pneumonia in leukocytopenic patients; Kiehl MG et al.; STUDY OBJECTIVES: Pneumonia during chemotherapy-induced leukocytopenia is a major cause of overall treatment failure in patients with hematologic malignancies . To improve outcome in these high-risk patients, early diagnosis of pulmonary infiltrates and institution of adequate antimicrobial treatment are mandatory . To identify patients with evolving pneumonia, we have prospectively studied the prognostic value of cytokine and complement measurements in early BAL samples from febrile leukocytopenic patients . DESIGN: Prospective, comparative study . SETTING: Hematology/oncology section of a university hospital . PATIENTS: Twenty-one patients with leukocytopenia (WBC count < 1.000/microL) following cytoreductive chemotherapy for malignant disorders . INTERVENTION: Early BAL sampling primarily for microbiologic diagnostic purposes . MEASUREMENTS AND RESULTS: Proinflammatory cytokines and activated complement components were measured in the BAL aspirates and the results were related to the prevalence or subsequent evolution of overt pneumonia . Of the 21 patients studied, 10 patients presented with overt pneumonia at BAL sampling (group A), 5 patients developed objective signs of pneumonia 3 to 5 days after BAL (group B), and 6 patients remained free of pneumonia during follow-up (group C) . In comparison with group C, patients in groups A and B both had distinctly elevated bronchoalveolar levels of tumor necrosis factor-alpha, interleukin-6, granulocyte colony-stimulating factor, C3a, and C5a . CONCLUSIONS: Cytokine and complement determinations in early BAL samples may aid in the identification of febrile leukocytopenic patients with evolving pneumonia 3 to 5 days prior to the manifestation of diagnostic clinical and radiographic signs.

Nihon Kyobu Shikkan Gakkai Zasshi, 1997 Aug, 35(8), 854 - 62
{Clinical and laboratory findings associated with the severity of community-acquired pneumonia}; Tanabe J et al.; To clarify the clinical features of severe community-acquired pneumonia, we retrospectively studied 121 patients treated at our hospital . We divided the patients into three groups, based on the severity, of their disease . Patients were put in the "mild" group (n = 56) if they recovered after treatment with antimicrobial agents only, they were put in the "moderate" group (n = 34) if the required oxygen therapy and recovered, and they were put in the "severe" group (n = 31) if they required mechanical ventilation . Age and underlying disease were recorded, as well as signs, symptoms, and laboratory data obtained during the first 24 hours after admission . The data indicated that the following nine findings were associated with the severity of disease: age of at least 65 years, an underlying disease of (31) the respiratory or central nervous system, dyspnea, a pulse rate of at least 90 beats per minute, a respiratory rate of at least 25 breaths per minute, an albumin concentration no greater than 3.5 g/dl, a blood urea nitrogen level of at least 20 mg/dl, a PaO2 no greater than 60 mmHg or an SaO2 no greater than 90%, and a high score on a scale of the extent of roentgenographic evidence of pulmonary infiltrates . Patients in whom these are found be managed carefully.

J Ind Microbiol Biotechnol, 1997 Aug, 19(2), 104 - 13
Microscopic study of migration of microbes in food-packaging paper and board; Suominen I et al.; The microbiological barrier properties of food-packaging paperboards, coated with polyethylene, mineral pigment or a biodegradable polymer and of high-density paper were examined with confocal laser scanning microscopy . The results show that the spatial distribution of microscopically observable bacterial cells was uneven inside the paperboard . The concentration in the interface between the polyethylene coating and the cellulose fibers was 100-200 times higher than inside the cellulose matrix . The bacteria in the interface and the mineral coating layer grew in response to access to food and moisture, whereas no growth was observed inside the fiber web, not even after extended exposure for up to 90 days . The paper and paperboards studied contained soluble nutrients (C:N:P 54:9:1 to 309:3:1) and no measurable antimicrobial activity . The factor limiting growth and migration of bacteria inside the fiber web was most likely limited access to free water, even under conditions of extensive wetting . The studied paperboards functioned as efficient barriers against translocation of microbes . The microbes residing between the paperboard and its polymer coating facing food, was the only potential site from which microbes could leak into food . This emphasizes the need for high hygienic quality of surface-sizing chemicals . Mineral-coating pigments were a source of microbes and their application behind the PE coating facing food is contraindicated.

Dig Dis Sci, 1997 Oct, 42(10), 2111 - 5
Metronidazole resistance reduces efficacy of triple therapy and leads to secondary clarithromycin resistance; Buckley MJ et al.; There has been a significant increase in the prevalence of H . pylori resistance to metronidazole in recent years, while clarithromycin resistance is still relatively rare . In this study we assessed: (1) the effect of primary H . pylori resistance to metronidazole and clarithromycin on the clinical efficacy of a one-week regimen consisting of omeprazole, metronidazole, and clarithromycin; and (2) the rate of acquisition of secondary antimicrobial resistance after treatment failure . Eighty-seven patients with duodenal ulceration or nonulcer dyspepsia were included in the study . The primary metronidazole and clarithromycin resistance rates were 35.6% and 3.4%, respectively (all three pretreatment clarithromycin resistant strains had concurrent metronidazole resistance) . H . pylori was eradicated in 81.6% of patients . The eradication rate for fully sensitive isolates was 98.2% (55/56) but was significantly reduced to 57.1% (16/28) for isolates that were resistant to metronidazole alone and 0% (0/3) in cases of dual resistance (P < 0.001) . Secondary resistance to clarithromycin was acquired in 58.3% of cases of treatment failure . In areas of high prevalence of primary metronidazole resistance, this is a significant cause of treatment failure with this triple therapy regimen . This leads to the selection of strains with dual resistance that are difficult to eradicate and may contribute to an increase in the prevalence of clarithromycin resistance . In such areas an alternative first-line treatment should be prescribed.

J Pharm Pharmacol, 1997 Oct, 49(10), 972 - 5
Enhanced anticancer therapy mediated by specialized liposomes; Dass CR et al.; It has been a central aim of experimental and clinical therapeutics to deliver therapeutic agents as close as possible to, or if possible within, a diseased cell . Such targeting achieves two major aims of drug delivery, the maximum dose of therapeutic agent to the diseased cell and avoidance of uptake by and, usually, accompanying side-effects to normal, healthy cells . Conventional liposomes, originally used for studies in membrane biophysics and biochemistry, have been used in therapy for the past two decades . However, when applied to deliver drugs into cells, conventional liposomes proved inefficient and so novel unconventional or specialized liposomes are constantly being prepared to enhance cell-specific delivery in-vivo . One possible way of achieving better targeting is combination of the positive attributes of more than one specialized type of liposome into one vesicle . Although a limited number of studies has examined the combined effect of such dual-specialty liposomes, more studies are warranted using appropriate models . Liposomes are composed of one, a few, or many concentric bilayer membranes which alternate with aqueous spaces . The drugs are encapsulated within the aqueous internal volume if they are hydrophilic or in the lipid bilayers if they are hydrophobic (Kim 1993) . Liposomes range in size from 25 nm to more than 20 microns (Sugarman & Perez-Soler 1992) . Depending on their solubility and method of formulation antimicrobial, cytotoxic and other conventional drugs, hormones, antigens, enzymes, genetic material, viruses and bacteria can be incorporated in either the aqueous or hydrophobic phase . This review discusses the types and characteristics of non-conventional liposomes used in various modes of cancer therapy, mainly chemotherapy and gene therapy . It concludes with suggestions on improving these novel liposomal to effect better targeting to cancer cells.

J Med Microbiol, 1997 Oct, 46(10), 873 - 8
Phenotypic characteristics and lipopolysaccharides of human and animal isolates of Fusobacterium necrophorum; Brown R et al.; As part of a collaborative study, six culture collection isolates and 50 coded isolates of Fusobacterium necrophorum were examined for the types of lipopolysaccharides (LPS) they contained, and to see if this related to their reactions in a range of phenotypic tests and their susceptibility to a panel of six antimicrobial compounds . The biotype B type strain, putative biotype B isolates and human isolates were predominantly coccobacillary, had rough type LPS and some of these isolates (8 of 26) required incubation for > 2 days to demonstrate lipase activity . The biotype A type strain, putative biotype AB isolates and most putative biotype A isolates (16 of 18) were predominantly rod-shaped, had either smooth LPS or low M(r) rough type LPS and all demonstrated lipase activity within 2 days . The other two putative biotype A isolates were coccobacillary and had rough type LPS, and one of these required incubation for > 2 days to demonstrate lipase activity . The results of these latter two isolates more closely resembled biotype B . A few isolates were asaccharolytic, but most fermented one or more of glucose, fructose, maltose and galactose . There was no correlation between fermentation pattern and LPS type, biotype or source of isolate (animal or human) but, with the exception of two abberant isolates, there was good correlation between cellular morphology, type of growth in liquid media and LPS type.

Curr Opin Pulm Med, 1996 May, 2(3), 206 - 12
Nosocomial pneumonia; LeBas SJ et al.; Nosocomial pneumonia remains a major cause of morbidity, mortality, and significant hospital cost despite continued refinements in antimicrobial treatment, improved methods for diagnosis, and better supportive and preventive measures . While clinical experience is considerable, appreciation of the epidemiologic and pathogenic factors responsible for NP development and pathogen selection are limited, and consensus regarding optimal prevention and diagnostic and therapeutic strategies is lacking . This article reviews the recent literature with an emphasis on significance, pathogenesis, etiology, and therapy of nosocomial pneumonia.

Curr Opin Pulm Med, 1996 May, 2(3), 218 - 27
Antimicrobial approaches to therapy for pneumonia; Mandell LA; Pneumonia remains a serious illness with significant associated morbidity and mortality . Parallelling our increased understanding of the etiology, epidemiology, and pathogenesis of pneumonia and the development of new antibiotics has been the frightening increase in the rate and extent of bacterial resistance . The prevalence of resistance has reached unprecedented levels in many countries, and we are facing the specter of infection by pathogens for which we have no effective treatment . To better understand some of the newer developments in this field, the discussion centers around the interactive triad of the host, pathogen, and drug . Pertinent developments relevant to each of these three areas are considered, along with a discussion of their clinical impact.

Curr Opin Pulm Med, 1996 May, 2(3), 161 - 5
Guidelines for the management of respiratory infection: why do we need them, how should they be developed, and can they be useful?
Niederman MS.
The management of respiratory infections is a complex and dynamic process, with many areas of controversy and numerous unresolved questions . In an apparent effort to deal with these issues, guidelines for care are being developed for a variety of infections including bronchitis, community-acquired pneumonia, hospital-acquired pneumonia, tuberculosis, HIV infection, and viral illness in immune-compromised patients . As the era of managed care approaches, guidelines will continue to emerge, and several questions about their utility must be answered . In this discussion, the rationale for the popularity of guidelines is examined, along with a review of the processes by which they are developed . Although evidence-based medicine has been suggested as a basis for this process, there are several problems with this approach . Most importantly, evidence-based medicine does not adequately allow for the incorporation of local experience, which is so vital in the management of respiratory infection because of the variability in bacteriology and antimicrobial susceptibilities in different practice settings . If a guideline is developed by a consensus of experts, and viewed as an hypothesis that can be modified based on local data collection, then it can be very useful and can lead to a number of potential benefits for patients with respiratory tract infection.

Curr Opin Pulm Med, 1995 May, 1(3), 194 - 201
Nosocomial pneumonia; Chastre J et al.; Despite many advances in infection control measures, nosocomial pneumonia remains a frequent complication in ventilator-dependent patients cared for in the intensive care unit . During the past year in review, many important articles have been published dealing with critical issues for the optimal management of such patients . Nasal cannulation for endotracheal and gastric intubation has been recognized as a major risk factor for nosocomial infection in patients requiring mechanical ventilation . Although selective digestive decontamination remains highly controversial due to the risk of selecting for multi-resistant microorganisms, the potential benefit of using sucralfate for prevention of late onset pneumonia appears promising . There has been relatively little progress made regarding the optimal management strategy to use in patients with suspected pneumonia, except that protected specimen brush and bronchoalveolar lavage techniques were both qualitatively and quantitatively demonstrated to reliably identify microorganisms present in the lung, even when the infection develops as a superinfection in a patient already receiving antimicrobial therapy . Antibiotic treatment of nosocomial pneumonia remains a complex undertaking, and further trials will be ultimately needed to clarify in which circumstances monotherapy can be safely used.

Curr Opin Pulm Med, 1995 May, 1(3), 188 - 93
Nosocomial pneumonia in the noncritical care setting; Whitson B et al.; The optimal approach to the recognition, management, and prevention of nosocomial pneumonia is evolving . A broad spectrum of potential pathogens is recognized in the hospital setting, and more invasive procedures have been developed in attempts to improve diagnostic accuracy . Newer, broad spectrum antimicrobial agents are continually introduced, yet the presence of resistant organisms is increasingly recognized . The reports released in the past year show physicians are making advances toward gaining a better understanding of this common infection.

Pharmazie, 1997 Oct, 52(10), 750 - 3
Synthesis and antimicrobial screening of some novel thiazoles, dithiazoles and thiazolylpyridines; Fahmy HT; Several thiazolines 2a-c, and 4-thiazolidinones 3a-c were synthesized through the reaction of the cyanoacetic acid hydrazide derivatives 1a-c with phenacyl bromides or chloroacetic acid, respectively . The dithiazoles 4a, b were obtained from 2a, b through their reaction with sulphur and phenyl isothiocyanate . The dithiazoles 6a, b were prepared from 4a through its reaction with dimethyl sulphate followed by reaction of the produced 2-methylthiothiazolium salt 5 with either malononitrile or ethyl cyanoacetate . The thiazolyl-pyridines 7a, b and 8a, b were obtained from 2a, b through their reaction with arylidene malonitrile and arylidene ethyl cyanoacetate, respectively . The prepared compounds were screened for their antibacterial and antifungal activities in vitro . Some of them showed weak effects.

Pharmazie, 1997 Oct, 52(10), 746 - 9
Synthesis and antimicrobial testing of novel oxadiazolylbenzimidazole derivatives; Habib NS et al.; Three novel series of oxadiazolylbenzimidazole derivatives have been prepared, namely 1-{(2-alkylthio or aralkylthio-1,3,4-oxadiazol-5-yl)methyl}-2-alkyl-1 H-benzimidazoles 3a-f; 1-{(3-substituted aminomethyl-2-thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl)methyl }-2-alkyl-1 H-benzimidazoles 4a-f and 1-{(2-substituted amino-1,3,4-oxidiazol-5-yl)methyl}-2-alkyl-1 H-benzimidazoles 6a-j . The antimicrobial testing of the prepared compounds was performed, some of them showed week activity.

J Vet Med Sci, 1997 Oct, 59(10), 911 - 5
Effects of central nervous stimulants on spino-bulbo-spinal reflex potentials in cats; Hara Y et al.; Effects of central nervous stimulants on the spino-bulbo-spinal reflex potential were evaluated in anesthetized intact cats, and compared with those on segmental spinal reflex potentials in anesthetized spinal cats . In spinal cats, strychnine augmented polysynaptic reflex potential, picrotoxin inhibited dorsal root reflex potential, aminopyrine potentiated mono- and poly-synaptic reflex potentials but inhibited dorsal root reflex potential, and 4-aminopyridine potentiated all the three types of segmental reflex potentials . A combination of fenbufen, a non-steroidal antiinflammatory agent, and enoxacin, a new quinolone antimicrobial, inhibited all the three types of segmental reflex potentials . In contrast, all these drugs consistently produced an augmentation of the spino-bulbo-spinal reflex potential in anesthetized intact cats . From these findings, we suggest that the spino-bulbo-spinal reflex potential may be used as an electrophysiological parameter for the evaluation of central nervous stimulants.

Arch Pharm (Weinheim), 1997 Aug, 330(8), 253 - 8
Synthesis and antimicrobial activity of new 1-benzylbenzimidazolium chlorides; Pernak J et al.; 1-Benzylbenzimidazole reacts with chloromethylalkyl ethers or sulfides or chloromethylcycloalkyl ethers to produce 3-alkoxymethyl-1-benzylbenzimidazolium or 3-alkylthiomethyl-1-benzylbenzimidazolium or 1-benzyl-3-cycloalkoxymethylbenzimidazolium chlorides in very good yields . All the 1-benzylbenimidazolium chlorides showed antimicrobial activity . The relationship between chemical structure and antimicrobial activity was analyzed by quantitative structure-activity relationships (QSAR).

J Antibiot (Tokyo), 1997 Sep, 50(9), 734 - 7
Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora . I . Taxonomy, fermentation, isolation, and biological activities; Romero F et al.; A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092 . Based on morphological, cultural, physiological, and chemical characteristics, strain L-13-ACM2-092 was ascribed to the genus Micromonospora . Thiocoraline showed a potent cytotoxic activity against P-388, A-549 and MEL-28 cell lines, and also a strong antimicrobial activity against Gram-positive microorganisms . This compound binds to supercoiled DNA and inhibits RNA synthesis.

Panminerva Med, 1997 Sep, 39(3), 240 - 3
Single-dose ceftriaxone versus multiple-dose cefuroxime for antimicrobial chemoprophylaxis in pleuropulmonary surgery; Ilic N et al.; The efficacy and safety of single-dose ceftriaxone and multiple-dose cefuroxime as antibiotic prophylaxis for pleuropulmonary surgery were compared in 160 patients undergoing thoracic surgery . 82 patients received a single-dose of 2 g ceftriaxone intravenous prior to surgery . Seventy-eight patients received 1.5 g of cefuroxime i.v . prior to surgery and 750 mg i.m . every 8 hours for the next 48 hours . Patients were observed daily for ten days postoperatively and monitored for signs of wound and systemic infections . Postoperative infections were studied in each treatment group . No adverse postoperative infections effects or laboratory abnormalities attributable to either drug were noted . Those results indicate that single-dose ceftriaxone was as effective and well-tolerated as a multiple-dose cefuroxime in preventing postoperative infections following pleuropulmonary surgery.

ASAIO J, 1997 Sep-Oct, 43(5), M475 - 81
Silver modification of polyethylene terephthalate textiles for antimicrobial protection; Tweden KS et al.; The safety and in vitro effectiveness of applying silver to polyethylene terephthalate fabric mechanical heart valve (MHV) sewing cuffs for the prevention of prosthetic valve endocarditis (PVE) were evaluated . PVE is an infrequent but grave complication of cardiac surgery associated with mortality rates potentially exceeding 50% . A poor response to antibiotic therapy is partly responsible for the high mortality rates . Silver is a well known antimicrobial agent with broad effectiveness . Preliminary in vitro microbial challenge studies of the coated fabric using the New York State 63 bacteriostatic test and Dow Corning Shake Flask test showed a > or = 97% reduction for most organisms tested . Sheep mitral valve replacement studies suggest comparable tissue ingrowth of uncoated and coated fabric with a more organized, thinner pannus formed on silver coated fabric . Low levels of silver were present in the serum at all time periods . These results indicate MHVs with silver coated cuffs may provide additional protection against PVE.

J Nat Prod, 1997 Oct, 60(10), 967 - 70
Laurencia rigida: chemical investigations of its antifouling dichloromethane extract; Konig GM et al.; From the CH2Cl2 extract of the temperate marine red alga, Laurencia rigida, which has antifouling properties, eight sesquiterpenes (1-8) were isolated . Of these, four (3-acetoxy-E-gamma-bisabolene (1), (-)-10 alpha-bromo-9 beta-hydroxy-alpha-chamigrene (2), rigidol (3), and (+)-(10S)-10-bromo-beta-chamigrene (4)), were shown to be new natural products . For the known compound deschloroelatol (5), reassignment of the 1H- and 13C-NMR data was found to be necessary on the basis of extensive NMR measurements . For elatol (6), complete 1H- and 13C-NMR data are also reported . The antimicrobial and antialgal activities of all isolates were assessed.

Eur J Drug Metab Pharmacokinet, 1997 Jul-Sep, 22(3), 193 - 9
A comparison of the pharmacokinetics of meropenem after intravenous administration by injection over 2, 3 and 5 minutes; Jones HK et al.; The pharmacokinetics of meropenem were determined in 9 healthy volunteers after the administration of 1 g dose by injection over 2, 3 or 5 min . Peak plasma concentrations were not significantly different across the three rates of administration and, due to the finite time required for complete mixing of the blood in the central compartment, did not always occur at the end of the injection . Overall exposure to meropenem was unchanged by the more rapid rates of administration . Plasma clearance, terminal half-life and volume of distribution were virtually unchanged . Within 10 min after the start of the injection, the plasma concentrations from all three injections were very similar indicating that dosing over 2, 3 or 5 min would result in similar antimicrobial cover and, therefore, comparable efficacy . Comparison of the data derived from the three injections indicated that rapid administration of meropenem did not appreciably alter its disposition pharmacokinetics . Tolerability of meropenem was unchanged with the more rapid administration rate.

Drugs, 1997, 54 Suppl 2, 16 - 22; discussion 28-9
Ancillary benefits of Mycobacterium avium-intracellulare complex prophylaxis with clarithromycin in HIV-infected patients; Jablonowski H et al.; Because of the significant morbidity and mortality associated with opportunistic infections, prophylaxis has become routine practice in the management of immunocompromised patients such as those with AIDS . Clarithromycin, an antimicrobial agent with a broad spectrum of activity against most common respiratory pathogens as well as many protozoa, has proven to be effective for both treatment and prophylaxis of Mycobacterium avium-intracellulare complex (MAC) infection in AIDS patients . Results of a large multinational placebo-controlled study suggest that clarithromycin for MAC prophylaxis provides additional benefits . In this study, clarithromycin statistically significantly reduced the incidence of Pneumocystis carinii pneumonia (5.3% of clarithromycin recipients vs 10.0% of placebo recipients; p = 0.021), community-acquired pneumonia (7.1 vs 13.0%; p = 0.010), Giardia lamblia infection (0.9 vs 2.9%; p = 0.048), and neoplastic diseases (1.8 vs 4.1%; p = 0.010) in AIDS patients with CD4+ counts of < or = 100 cells/microliter.

Biochim Biophys Acta, 1997 Sep 5, 1341(2), 105 - 7
Sequence analysis of the cDNA encoding the precursor of equinatoxin V, a newly discovered hemolysin from the sea anemone Actinia equina; Pungercar J et al.; A cDNA encoding the 214-amino-acid (aa) precursor of equinatoxin V (EqtV) has been isolated from an Actinia equina cDNA library . The sequence of the mature toxin is preceded, as that of EqtII, by a signal peptide of 19 aa and a hydrophilic propeptide of 16 aa ending with a pair of basic residues . This is similar to the precursors of calitoxins from another sea anemone Calliactis parasitica and to those of some antimicrobial peptides of the magainin and dermaseptin families from vertebrates . The deduced aa sequence of the potential cell attachment Arg-Gly-Asp motif-containing EqtV shows 82% identity to that of EqtII.

Indian Pediatr, 1997 Jun, 34(6), 527 - 34
Experience with diarrhea training and treatment unit in Shimla; Bahl L et al.; PIP: India's National Program for Control of Diarrheal Diseases has established Diarrhea Training and Treatment Units (DTUs) to reduce diarrhea-related morbidity and mortality . The cost-effectiveness and impact of oral rehydration therapy (ORT) were evaluated prospectively in all children presenting to the DTU of I.G . Medical College (Shimla, India) in 1993-94 . During the 2-year study period, a total of 1240 children 1 month to 12 years of age attended this DTU for treatment . 47.6% were infants and 58% came from rural areas . 87% of patients had acute watery diarrhea, 10.4% had dysentery, and 2.6% had persistent diarrhea . Diarrhea was most prevalent (74.9%) from April to September . 41.9% of presenting children had received ORT before coming to the DTU; as a result, severe dehydration was seen in only 10.7% of cases . Comparison of data on 166 children admitted to the study hospital in 1986-87 (before ORT was introduced) and the 1993-94 cases revealed significant declines in the admission rate due to dehydration and/or associated illnesses (100% vs . 26.8%), use of antimicrobials (66.2% vs . 15.3%), administration of intravenous fluids (71.1% vs . 15.45%), and mortality (9.03% vs . 0.6%) . 84.6% of children in 1993-94 were treated with ORT alone . The average cost of ORT per child was Rs . 4.49 compared with Rs . 40.29 for intravenous fluids . Although these findings indicate DTUs are having a favorable impact on the rational management of diarrhea, health education campaigns aimed at promoting even more widespread use of ORT by mothers and health workers are needed .

Clin Infect Dis, 1997 Oct, 25(4), 888 - 95
Iron, infections, and anemia of inflammation; Jurado RL; Iron is essential to all microorganisms . To obtain iron from the very low concentrations present in their environment, microorganisms have developed sophisticated mechanisms such as the siderophore system . As a primitive defense mechanism, humans have developed mechanisms to withhold iron from microorganisms . Iron-binding proteins such as transferrin, ferritin, and lactoferrin have a central role in human ferrokinetics . These iron-binding proteins also participate in the process of decreasing iron availability for the microorganisms . They do so by decreasing iron reutilization . Anemia of inflammation (previously called anemia of chronic disease) is seen in the setting of infectious, inflammatory, and neoplastic diseases . It results, in part, from changes in the intracellular metabolism of iron . Alterations of iron physiology seen in many clinical circumstances make excess iron available to microorganisms, thus enhancing their pathogenicity . Understanding the molecular basis of iron withholding by the human host, both in the absence of and during infection, and that of iron acquisition by microorganisms may provide us with new and innovative antimicrobial agents and vaccines.

Clin Infect Dis, 1997 Oct, 25(4), 858 - 70
The clinical microbiology laboratory and infection control: emerging pathogens, antimicrobial resistance, and new technology; Pfaller MA et al.; The clinical microbiology laboratory is an essential component of an effective infection control program . Laboratory personnel have a broad range of technologies, from traditional methods of detecting and identifying organisms to modern molecular typing methods, that they can use to support and enhance the efforts of the infection control staff . If the infection control team applies these technologies appropriately, it can prevent problems and solve nosocomial mysteries efficiently . In this era of cost-containment, staff members in the laboratory and in the infection control program must work hard to communicate their unique and shared goals, needs, and problems . If the laboratory and infection control personnel cooperate and collaborate rather than compete, both programs will be successful and the patients and the hospital will benefit because the risk of nosocomial infections and the frequency of resistant organisms will be reduced.

Clin Infect Dis, 1997 Oct, 25(4), 787 - 801
Practice guidelines for community-based parenteral anti-infective therapy . ISDA Practice Guidelines Committee; Williams DN et al.; This is the fourth in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee . The purpose of this guideline is to provide assistance to clinicians when making decisions on when and how to best administer parenteral antimicrobial therapy . The targeted providers are internists, pediatricians, family practitioners, and other providers of outpatient antiinfective therapy . Criteria for selecting the appropriate patients and settings to deliver therapy in the community are described . Panel members represented experts in adult and pediatric infectious diseases . The guidelines are evidence-based . A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed . The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council . An executive summary and tables highlight the major recommendations.

Clin Infect Dis, 1997 Oct, 25(4), 763 - 79; quiz 780-1
Brain abscess; Mathisen GE et al.; The past 20 years have seen major advances in the diagnosis and management of brain abscess, with a corresponding improvement in the survival rates . The advances in radiographic scanning, the availability of new antimicrobials, and the development of novel surgical techniques have all contributed to the decreases in associated morbidity and mortality . The relative rarity of brain abscess and the frequent delays in making the diagnosis render this condition a significant challenge for the clinician . A high index of suspicion is required so that effective therapy can be instituted as soon as possible . Close coordination of care between neurosurgeons and infectious diseases specialists is increasingly important in the complicated management of brain abscess . Adequate abscess drainage and appropriate antimicrobial therapy remain the cornerstones of proper treatment of this condition.

Indian J Med Sci, 1997 Jun, 51(6), 196 - 203
Infectious diarrhoea--an update; Ram S et al.; Infectious diarrhoea is one of the most common illness affecting mankind . Recent advancement have led to detailed understanding of causative agents and the pathogenesis of the infections . Fluid and electrolyte replacement remains the most important aspect of treatment . The role of antimicrobial agents is discussed.

Aliment Pharmacol Ther, 1997 Oct, 11(5), 939 - 42
Clarithromycin, amoxycillin and H2-receptor antagonist therapy for Helicobacter pylori peptic ulcer disease in Korea; Breuer T et al.; BACKGROUND: Effective anti-Helicobacter pylori therapies with few side-effects are needed . We previously showed that the regimen of amoxycillin, clarithromycin and an H2-receptor antagonist was effective in the United States . The current study tested whether this therapy would also be successful in Korea . METHODS: Patients with gastric or duodenal ulcers received amoxycillin (750 mg t.d.s.) plus clarithromycin (500 mg t.d.s.) for 2 weeks and nizatidine 300 mg at bedtime for 6 weeks . Endoscopic examinations were performed before treatment and 4 or more weeks after ending antimicrobial therapy . H . pylori status was confirmed by rapid urease testing and histological examination of gastric antrum and corpus biopsies using the Genta stain . Antibiotic resistance was tested using the E-test method . Cure was defined as no evidence of H . pylori infection 4 or more weeks after ending therapy . RESULTS: Seventy-two patients (59 males and 13 females; mean age 46 years), including 35 with duodenal ulcers, 30 with gastric ulcers and seven with both, were studied . H . pylori infection was cured in 95.8% (69/72 patients; 95% CI = 88.3-99.1%) . Two of the treatment failures had culture data and one had pre-treatment resistance to clarithromycin . Smoking did not have an adverse effect on therapy . Ten patients (15%) developed side-effects during treatment, but all were mild and did not require treatment interruption . No case of reinfection was noted during follow-up . CONCLUSION: The combination of amoxycillin, clarithromycin and an H2-receptor antagonist is effective in Korean patients with H . pylori infection.

Aliment Pharmacol Ther, 1997 Oct, 11(5), 935 - 8
Twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) for treatment of Helicobacter pylori infection; Graham DY et al.; BACKGROUND: Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being > 95% effective, regardless of metronidazole resistance . We tested a 10-day b.d . quadruple therapy for treatment of H . pylori infection . METHODS: Anti-H . pylori therapy consisted of lansoprazole 15 mg b.d . plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto-Bismol caplets (2 b.d.) for 10 days . H . pylori status was evaluated by culture and histology before and 4 or more weeks after therapy . RESULTS: The cure rate for intention-to-treat was 70% . Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns . The cure rate among the metronidazole-sensitive isolates was 89.7% (26 of 29) vs . 41.2% (7 of 17) of the metronidazole-resistant isolates (P < 0.005) . Moderate (n = 1) or severe (n = 3) side-effects were experienced in four patients with only one withdrawing because of side-effects . CONCLUSION: Twice a day quadruple therapy is effective for metronidazole-sensitive strains but its usefulness is markedly reduced by the presence of pre-treatment metronidazole resistance . Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon . Possibly, 14-day therapy or a higher dosage of metronidazole provide better results with metronidazole-resistant H . pylori.

Microbiology, 1997 Oct, 143 ( Pt 10), 3123 - 36
A geographically widespread plasmid from Thiobacillus ferrooxidans has genes for ferredoxin-, FNR-, prismane- and NADH-oxidoreductase-like proteins which are also located on the chromosome; Dominy CN et al.; During a search for genes encoding electron transport proteins from a Thiobacillus ferroxidans ATCC 33020 gene bank, a 19.8 kb plasmid, pTF5, which conferred increased sensitivity to the antimicrobial agent metronidazole upon an Escherichia coli mutant, was isolated and cloned in E . coli . The plasmid had an identical restriction enzyme map to a plasmid which has been found in T . ferrooxidans strains isolated from many different parts of the world . The plasmid was present at between two and four copies per genome and contained a region of approximately 5-6 kb which was also found on the chromosome . This region was sequenced and found to have four complete ORFs, which when translated had high percentage amino acid similarity to {3Fe-4S,4Fe-4S} ferredoxins, proteins of the FNR regulator family, prismane-like proteins and the NADH oxidoreductase subunit of a methane monooxygenase . In vitro protein analysis using an E . coli-derived transcription-translation system indicated that three of the four products (FdxA, PsmA and RedA) were expressed in the heterologous system . Ferredoxins, prismane-like proteins and NADH oxidoreductases are redox-active proteins and it is likely that the proteins on pTF5 represent an electron transport system of as yet unknown function . Surprisingly, although genes for redox-active proteins have been isolated from other bacteria by screening gene banks for increased sensitivity to metronidazole, the region of pTF5 containing the genes for these proteins was not responsible for the increase in metronidazole sensitivity conferred by the plasmid . The region of pTF5 which did confer increased metronidazole sensitivity to an E . coli metronidazole-resistant mutant was a 319 bp region of DNA close to the origin of plasmid replication . This region contained no ORFs and was identical to that previously reported for the replicon of a 9.8 kb T . ferrooxidans plasmid, pTF191.

J Biol Chem, 1997 Nov 7, 272(45), 28398 - 406
Penaeidins, a new family of antimicrobial peptides isolated from the shrimp Penaeus vannamei (Decapoda); Destoumieux D et al.; We report here the isolation of three members of a new family of antimicrobial peptides from the hemolymph of shrimps Penaeus vannamei in which immune response has not been experimentally induced . The three molecules display antimicrobial activity against fungi and bacteria with a predominant activity against Gram-positive bacteria . The complete sequences of these peptides were determined by a combination of enzymatic cleavages, Edman degradation, mass spectrometry, and cDNA cloning using a hemocyte cDNA library . The mature molecules (50 and 62 residues) are characterized by an NH2-terminal domain rich in proline residues and a COOH-terminal domain containing three intramolecular disulfide bridges . One of these molecules is post-translationally modified by a pyroglutamic acid at the first position . Comparison of the data obtained from the cDNA clones and mass spectrometry showed that two of these peptides are probably COOH-terminally amidated by elimination of a glycine residue . These molecules with no evident homology to other hitherto described antimicrobial peptides were named penaeidins.

Am J Clin Pathol, 1997 Nov, 108(5), 504 - 9
Is the sanctuary where Helicobacter pylori avoids antibacterial treatment intracellular?
Engstrand L, Graham D, Scheynius A, Genta RM, El-Zaatari F.
The sanctuary site where Helicobacter pylori evades antimicrobial therapy is unknown, but considerable data exist about an intracellular location for H pylori . Ten H pylori-infected volunteers received standard triple antimicrobial therapy for 2 weeks . Gastric mucosal biopsy specimens were obtained with jumbo forceps on therapy days 0, 3, 14, and 42 . Hematoxylin-eosin staining was used for classification of gastritis and the Genta stain for the visualization of H pylori . Immunohistochemical staining was used to detect HLA-DR antigens, human heat shock protein (HSP60), and the bacterial HSP60 antigen . Bacterial HSP60 was expressed on the mucosal surface and within epithelial cells . No such expression of human HSP60 was found, which supports a bacterial origin for the intracellular HSP60 . Coexpression of bacterial HSP60 and HLA-DR was always observed, indicating an ongoing local immune response . Infection was cleared on day 14, but when examined 4 weeks after completion of therapy, Genta staining indicated that only five volunteers remained free of H pylori . However, results of immunohistochemical staining were negative at this time for only two volunteers . Disappearance of intracellular expression of bacterial HSP60 remained after therapy and correlated with the intensity of chronic inflammatory cell infiltration . These data are consistent with the intracellular localization of H pylori having a role in inflammation and as a protective strategy against extracellular antibacterial activity.

Gastroenterology, 1997 Nov, 113(5), 1779 - 84
Paneth cells and innate immunity in the crypt microenvironment; Ouellette AJ; Paneth cells release granules into the lumen of the crypts of Lieberkuhn in the small intestine where their component proteins participate in mucosal immunity . The granules contain a number of proteins associated with roles in host defense, including lysozyme, secretory phospholipase A2, and alpha-defensins, termed cryptdins . Mouse cryptdins 1-6 and recombinant human Paneth cell alpha-defensin HD-5 are potent antimicrobial agents against certain microorganisms . As defensins, they kill microbes by disruption of the target cell membrane . The peptides are coded by individual, two-exon genes that map to homologous regions of chromosome 8 in mice and humans, and the differential expression of certain mouse cryptdin genes provides markers for studies of crypt ontogeny and epithelial cell differentiation and lineage determination . Neutrophil alpha-defensin peptides exhibit numerous biological activities in addition to antimicrobial function including regulation of cell volume, chemotaxis, mitogenicity, and inhibition of natural killer cell activity . When administered apically, mouse cryptdins 2 and 3 can reversibly stimulate human T-84 intestinal epithelial cells to secrete chloride ion, suggesting that alpha-defensins from Paneth cells also may be multifunctional . Thus, cryptdins and varied Paneth cell secretory products seem to contribute both to innate immunity of the crypt lumen and to defining the apical environment of neighboring cells.

Microbiol Res, 1997 Sep, 152(3), 239 - 46
Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria; Mirzoeva OK et al.; The effect of the natural bee product propolis on the physiology of microorganisms was investigated using B . subtilis, E . coli and R . sphaeroides . An ethanolic extract of propolis had a bactericidal effect caused by the presence of very active, but labile, ingredients . The exact bactericidal effect of propolis was species dependent: it was effective against gram-positive and some gram-negative bacteria . Propolis and some of its cinnamic and flavonoid components were found to uncouple the energy transducing cytoplasmic membrane and to inhibit bacterial motility . These effects on the bioenergetic status of the membrane may contribute to the antimicrobial action of propolis and its observed synergism with selected antibiotics.

Int J Clin Pharmacol Ther, 1997 Oct, 35(10), 426 - 33
Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations; Dalla Costa T et al.; PURPOSE: The aim of the study was to investigate the in vitro antiinfective effect of piperacillin-tazobactam (PIP-TZB) combinations on Escherichia coli in simulations of free concentration time profiles of both drugs, similar to those obtained in human tissue after i.v . bolus administrations . METHODS: An in vitro dilution model was used to expose E . coli ATCC 35218 (beta-lactamase producer) to various piperacillin-tazobactam concentration profiles obtained after i.v . bolus multiple dose, using different dose ratio combinations (1:4, 1:8, 1:16) and dosing regimens, ranging from once-a-day to 4 times a day . The antimicrobial effect was evaluated by determination of the number of bacteria over time . The concentration of PIP in the model was determined by HPLC . RESULTS: A modified Emax model was used to describe the pharmacodynamic effect . The model was linked with the piperacillin concentrations determined experimentally to provide a pharmacokinetic-pharmacodynamic (PK-PD) model . The EC50 for piperacillin alone averaged 5.66 +/- 0.29 micrograms/ml . The EC50 for all doses of piperacillin combined with 0.5 g of tazobactam were dose-dependent and averaged 1.70 +/- 0.56, 3.95 +/- 1.02, and 6.14 +/- 1.24 micrograms/ml for PIP 2, 4, and 8 g, respectively . By increasing the dose of TZB in combination with a fixed dose of PIP, a decreased EC50 was observed . CONCLUSIONS: The PK-PD model allowed a detailed evaluation of the dosing regimens investigated . The results suggested that for these combinations, 3 times a day administration is as effective as 4 times a day . Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations.

Eur J Ophthalmol, 1997 Jul-Sep, 7(3), 223 - 8
Causes of enucleation: a clinicopathological study; Gunalp I et al.; BACKGROUND: Enucleation is an approach used for unresponsive end-stage ocular disease often resulting in blind, painful or cosmetically unacceptable eyes . METHODS: We reviewed the clinicopathological data on 3506 enucleations performed over a 50-year period, 1945-1995 . Histopathological data were divided into eight groups according to the causes leading to enucleation: trauma, phthisis, corneal disease, inflammation, vitreoretinal disease, glaucoma, tumors and infections . RESULTS: The study considered 3506 enucleated eyes of 3482 patients, 2467 (70.8%) males and 1011 (29.1%) females (4 sex unspecified) . The z-test showed there were significantly more enucleations in males for phthisis (p < 5.05), infections (p < 0.01), trauma (p < 0.01) and inflammation (p < 0.01) and more enucleations for tumors in females (p < 0.01) . There were no differences between males and females with regard to enucleations for glaucoma, vitreoretinal and corneal diseases (p > 0.05) . The 0-9 years age group was most frequently affected, accounting for 29.7% of the cases . Patients aged less than 30 years constituted 53.6% of all enucleations . The primary or underlying causes leading to enucleation were tumors (1185 eyes, 33.8%), phthisis (587 eyes, 16.7), glaucoma (561 eyes, 16.0%), vitreoretinal diseases (320 eyes, 9.1%), infections (259 eyes, 7.4%), corneal disease (229 eyes, 6.5%), trauma (209 eyes, 6.0%) and inflammation (156 eyes, 4.4%) . Time trends in enucleating eyes with different causes showed the number of enucleations for phthisis, infections, corneal diseases, trauma and inflammations had dropped during the ten-year period 1986-1995 compared to 1976-1985 (z-test, p < 0.01) . There were no real changes in enucleations for glaucoma and vitreoretinal diseases and there was an increase in the number of enucleations for tumors (p < 0.01) . CONCLUSIONS: Improved diagnostic and therapeutic methods, widespread use of photocoagulation in vascular disorders and vitreoretinal surgery in traumas, effective antimicrobial treatment, increasing use of corticosteroids and immunosuppressants, have contributed to the decreasing frequency of enucleation . Tumor patients generally presented late with advanced tumors totally filling the eye, not salvageable by other non-invasive treatment methods . Prompt diagnosis of intraocular malignant tumors (retinoblastoma and malignant melanoma) may reduce the need for enucleation.

Eur J Clin Chem Clin Biochem, 1997 Sep, 35(9), 647 - 54
Biological functions of haptoglobin--new pieces to an old puzzle; Dobryszycka W; Haptoglobin, an "acute phase" protein, has different functions, which display genetic polymorphism . The complex of haptoglobin with haemoglobin is metabolized in the heptic reticuloendothelial system . Biosynthesis of haptoglobin occurs not only in the liver, but also in adipose tissue and in lung; providing antioxidant and antimicrobial activity . Changes in the measured concentrations of haptoglobin in serum may help to assess the disease status of patients with inflammations, infections, malignancy etc . (increases) as well as in haemolytic conditions (decreases) . Haptoglobin plays a role in stimulation of angiogenesis and has highly potent cholesterolcrystallization-promoting activity . Probably the most important biological function of haptoglobin consists in the host defence responses to infection and inflammation, acting as a natural antagonist for receptor-ligand activation of the immune system.

Am J Respir Crit Care Med, 1997 Oct, 156(4 Pt 1), 1247 - 55
Contrasting effects of hypochlorous acid and hydrogen peroxide on endothelial permeability: prevention with cAMP drugs; Ochoa L et al.; Activated polymorphonuclear leukocytes generate a cascade of reduced oxygen metabolites . In addition to their antimicrobial role, hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) function as inflammatory mediators and increase the protein permeability of the vascular endothelium . The objectives of the present study were to compare the effects of H2O2 and HOCl with respect to relative potencies and the time course and magnitude of changes in cell shape and permeability of endothelial cell monolayers derived from bovine pulmonary artery, to determine if HOCl produced by conversion of H2O2 with myeloperoxidase and Cl- produces comparable results as the direct administration of HOCl, and to show that adenosine 3',5'-cyclic monophosphate (cAMP)-enhancing agents can prevent the increased endothelial permeability induced by HOCl and H2O2 . HOCl given directly or produced by myeloperoxidase, H2O2, and Cl- caused faster and greater changes in cell shape (cell retraction), electrical resistance, and protein permeability (125I-labeled albumin clearance) of endothelial cell monolayers than induced by H2O2 . HOCl (10 to 100 microM) induced these changes within 1 to 3 min, whereas H2O2 (50 to 400 microM) required approximately 30 min . 8-Bromo-cAMP prevented the increased endothelial protein permeability induced by HOCl or H2O2, but isoproterenol only prevented the H2O2 response . Thus, HOCl at a much lower concentration caused a faster and greater increase in endothelial permeability in vitro than H2O2, and an increased intracellular level of cAMP prevented the increased permeability induced by either oxidant.

Am J Respir Crit Care Med, 1997 Oct, 156(4 Pt 1), 1092 - 8
Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: incidence and diagnosis; Delclaux C et al.; Ventilator-associated pneumonia (VAP) is difficult to detect and is often unsuspected during adult respiratory distress syndrome (ARDS) . We prospectively evaluated lower respiratory tract (LRT) colonization and infection in 30 patients with severe ARDS (PaO2/FIO2 ratio < 150 mm Hg), using repeated quantitative cultures of plugged telescopic catheter (PTC) specimens taken blindly via the endotracheal tube every 48 to 72 h after onset of ARDS . All patients except one were receiving antibiotics . When VAP was suspected on the presence of clinical criteria for infection, a repeated PTC and, when possible, a bronchoalveolar lavage (BAL) were obtained before any new antimicrobials were administered; samples growing > or = 10(3) cfu/ml (PTC) or > or = 10(4) cfu/ml (BAL) were considered diagnostic of infection . Twenty-four VAP episodes were diagnosed in 18 patients (60% of patients or 4.2/100 ventilator-days) a mean of 9.8+/-5.7 d after onset of ARDS . Eighteen LRT colonization episodes were recorded; 16 of 24 (66%) VAP episodes were preceded (by 2 to 6 d) by LRT colonization with the same organism(s), and only two episodes of colonization were not followed by VAP . We conclude that although VAP is of relatively late-onset during severe ARDS, its incidence is much higher than in other conditions and can be underestimated . Lower airways colonization is consistently followed by infection with the same organisms and precedes VAP in two thirds of episodes . Repeated protected specimens taken blindly may provide a useful means to predict infection and therefore allow early antimicrobial therapy in high-risk patients with diffuse lung injury.

J Appl Microbiol, 1997 Sep, 83(3), 322 - 6
Evaluation of preservative effectiveness in pharmaceutical products: the use of a wild strain of Pseudomonas cepacia; Zani F et al.; A sodium benzoate-sorbic acid preservative system of a pharmaceutical product was proved effective against a wild strain of Pseudomonas cepacia, following the official method of the Italian and British Pharmacopoeias . However, this preservative system was ineffective against a challenge of Ps . cepacia wild strain cells grown in the unpreserved pharmaceutical product and on culture media different from those described by the Pharmacopoeias . The adaptive resistance of the wild strain of Ps . cepacia was not demonstrated with a laboratory strain (ATCC 25609) . In contrast, p-hydroxybenzoate-based preservative systems proved to be efficient in protecting the pharmaceutical product against a challenge of wild and laboratory strains of Ps . cepacia grown in the different conditions described above . The results obtained suggest the usefulness, in the official methods for testing pharmaceutical preservatives, of using wild microbial strains isolated from the pharmaceutical environment . Metabolic adaptive responses, capable of affecting the antimicrobial sensitivity of wild micro-organisms used to challenge the preserved product, can be detected by using cells grown in the unpreserved pharmaceutical product.

Diagn Microbiol Infect Dis, 1997 Sep, 29(1), 55 - 7
Anti-Legionella activity of trovafloxacin compared with seven other antimicrobial agents including an intermethod evaluation; Marco F et al.; The activity of trovafloxacin, a new fluorinated naphtheridone, was tested against 61 Legionella spp . isolates and compared with that of 4 fluoroquinolones, 2 macrolides, and rifampin . Trovafloxacin MICs were determined by a reference agar dilution method and E-test (Solna, Sweden) strips on buffered charcoal yeast extract agar . Among the fluoroquinolone compounds, the rank order of activity (on the basis of MIC90 results) determined with E-test strips was as follows: levofloxacin (MIC90, 0.094 microgram/ml) > trovafloxacin = sparfloxacin = ofloxacin (MIC90, 0.19 microgram/ml) . Rifampin (MIC90, 0.008 microgram/ ml) and clarithromycin (MIC90, 0.032 microgram/ml) were the most potent of all drugs tested, and erythromycin and ciprofloxacin were the least active . In this study, the E-test strips with trovafloxacin were validated (100% of results +/- one log2 dilution compared to the reference value) for susceptibility testing with Legionella isolates.

CMAJ, 1997 Mar 15, 156 Suppl 6, S1 - 14
A practical guide for the diagnosis and treatment of acute sinusitis; Low DE et al.; OBJECTIVE: To develop guidelines for the diagnosis and management of acute sinusitis . OPTIONS: Diagnostic clinical criteria and imaging techniques, the role of antimicrobial therapy and duration of treatment, and the role of adjunct therapy, including decongestants, glucocorticosteroids and nasal irrigation . OUTCOMES: Improved accuracy of clinical diagnosis, better utilization of imaging techniques and rational use of antimicrobial therapy . EVIDENCE: A MEDLINE search for relevant articles published from 1980 to 1996 using the MeSH terms "sinusitis," "acute sinusitis," "respiratory infections," "upper respiratory infections," "sinusitis" and "diagnosis," "sinusitis" and "therapy," "sinusitis" and "etiology," and "antimicrobial resistance" and search for additional articles from the reference lists of retrieved articles . Papers referring to chronic sinusitis, sinusitis in compromised patients and documented nonbacterial sinusitis were excluded . The evidence was evaluated by participants at the Canadian Sinusitis Symposium, field in Toronto on April 26-27, 1996 . VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used . Strategies were identified to deal with problems for which no adequate clinical data were available . Recommendations arrived at by consensus of the symposium participants were included . BENEFITS, HARMS AND COSTS: Increased awareness of acute sinusitis, accurate diagnosis and prompt treatment should reduce costs related to unnecessary investigations, time lost from work and complications due to inappropriate treatment . As well, physicians will be better able to decide which patients will not require antimicrobial therapy, thus saving the patient the cost and potential side effects of treatment . RECOMMENDATIONS: Clinical diagnosis can usually be made from the patient's history and findings on physical examination only . Five clinical findings comprising 3 symptoms (maxillary toothache, poor response to decongestants and a history of coloured nasal discharge) and 2 signs (purulent nasal secretion and abnormal transillumination result) are the best predictors of acute bacterial sinusitis (level I evidence) . Transillumination is a useful technique in the hands of experienced personnel, but only negative findings are useful (level III evidence) . Radiography is not warranted when the likelihood of acute sinusitis is high or low but is useful when the diagnosis is in doubt (level III evidence) . First-line therapy should be a 10-day course of amoxicillin (trimethoprim-sulfamethoxazole should be given to patients allergic to penicillin) (level I evidence) and a decongestant (level III evidence) . Patients allergic to amoxicillin and those not responding to first-line therapy should be switched to a second-line agent . As well, patients with recurrent episodes of acute sinusitis who have been assessed and found not to have anatomic anomalies may also benefit from second-line therapy (level III evidence) . VALIDATION: The recommendations are based on consensus of Canadian and American experts in infectious diseases, microbiology, otolaryngology and family medicine . The guidelines were reviewed independently for the advisory committee by 2 external experts . Previous guidelines did not exist in Canada.

J Med Chem, 1997 Sep 26, 40(20), 3292 - 6
DNA gyrase inhibitory and antimicrobial activities of some diphenic acid monohydroxamides; Ohemeng KA et al.; The synthesis and inhibitory activity against DNA gyrase of a series of diphenic acid monohydroxamides 4a-f are described . A protocol of two biological assays showed conclusively that inhibition occurs specifically at the DNA-DNA gyrase complex and is not attributable to nonspecific inhibition . In the enzyme assays, 4c was potent as the prototypical quinolone, nalidixic acid (1), with an IC50 value of 58.3 micrograms/mL compared to 52 micrograms/mL for 1 . MIC activity against bacterial strains showed a systematic drop for all compounds relative to 1 . For compounds 4c-e, the addition of PMBN produced dramatic increases in MIC activity indicating that activity is likely to be related to membrane transport . Molecular modeling of 4a indicates that the diphenic acid monohydroxamides can bind to the DNA-DNA gyrase complex in a similar fashion as that hypothesized for the quinolone series according to the hypothesis suggested by Shen et al . but may not self-associate by pi-pi stacking . In contrast to the quinolone series, as the diphenic acid monohydroxamides are shown by molecular mechanics minimizations to be nonplanar, they may present novel approaches for chemotherapeutic intervention with a potential for decreased side effects.

J Inorg Biochem, 1997 Oct, 68(1), 39 - 44
Ag(I)-N bond-containing compound showing wide spectra in effective antimicrobial activities: polymeric silver(I) imidazolate; Nomiya K et al.; A neutral, Ag(I)-N bonding compound, polymeric silver(I)-imidazolate {Ag(imd)}n (1) consisting of Ag+: imd = 1:1 (Himd = imidazole, C3H4N2), showed wide spectra in effective antimicrobial activities against bacteria, yeast and mold . Of particular note are the activities against a wide range of mold . This polymeric solid does not crystallize and is sparingly soluble in all solvents . The monomeric, cationic, water-soluble Ag(I)-N bonding complex, {Ag(Himd)2}(NO3) (2), has also shown wide spectra of effective antimicrobial activities . These activities observed here were significantly different from those of the recently prepared oligomeric Ag(I)-S bonding complexes; the latter have shown narrow spectra . It is proposed that the Ag(I)-N bonding is one of the key factors showing the wide spectra of antimicrobial activities and the potential targets for inhibition of bacteria and yeast by these Ag(I) complexes are proteins, but not nucleic acids . The physico-chemical properties of (1), in comparison with those of (2), with various measurements (FT-IR, Laser Raman scattering spectroscopy, ESCA and solid 13C CP-MAS NMR spectroscopies) are described.

Clin Ther, 1997 Jul-Aug, 19(4), 626 - 38; discussion 603
Treatment of nontuberculous mycobacterial infections: role of clarithromycin and azithromycin; Tartaglione T; The incidence of identification of nontuberculous mycobacteria has increased since the advent of the acquired immunodeficiency syndrome epidemic . Although Mycobacterium avium complex appears to be responsible for most episodes of nontuberculous disease, several other previously rare species are increasingly being detected, including Mycobacterium kansasii, Mycobacterium fortuitum/chelonei complex, and Mycobacterium genavense . This review briefly summarizes the epidemiology and clinical features of these infections, as well as therapeutic and preventive strategies in immunosuppressed patients with nontuberculous mycobacterial infections . Of clinical relevance, nontuberculous mycobacterial infections are difficult to treat and do not respond to traditional antituberculous agents . The search for more effective treatment regimens is ongoing in an attempt to enhance survival and reduce morbidity among immunocompromised patients . Novel antimicrobial combinations that include clarithromycin or azithromycin have been shown to be effective in treating several nontuberculous mycobacterial infections.

Semin Hematol, 1997 Oct, 34(4), 343 - 54
Antimicrobial peptides of phagocytes and epithelia; Ganz T et al.; Human and other vertebrate leukocytes contain multiple distinct antimicrobial (poly)peptides . Of these, BPI is a LPB protein active against gram-negative bacteria, PLA2 specifically cleaves bacterial phospholipids, while defensins and cathelicidins are broad spectrum antimicrobials that preferentially permeabilize microbial membranes . These and other polypeptides function in both phagocytic and extracellular killing of microbes, attacking multiple molecular targets to cooperatively penetrate and disrupt the microbial surfaces and membrane barriers . Such antimicrobial substances are of interest not only for students of phagocytic and epithelial host defenses but may lead to the development of novel pharmaceuticals for the treatment of infections and their sequellae.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1997 Oct, 84(4), 372 - 80
Oral keratinocyte immune responses in HIV-associated candidiasis; Eversole LR et al.; INTRODUCTION: Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects . The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis . MATERIAL/METHODS: This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis . Oral biopsy specimens from lesional tissues were procured, and histopathologic features were correlated with immunohistochemical and in situ hybridization investigations for the expression of interleukin 1 alpha, interleukin 8, antimicrobial calprotectin, lymphocyte populations, and Candida antigen . RESULTS: Both pseudomembranous and erythematous candidiasis among HIV-infected subjects showed a mild interface lymphocytic mucositis with the presence of neutrophilic subcorneal abscesses in the latter . Erythematous candidiasis cases that failed to show surface mycelia, did yield positive results for Candida antigens in the parakeratinized layer . The expression of inflammatory chemokines were positive in all groups and calprotectin appeared to serve as a keratinocyte barrier to hyphal penetration . CONCLUSIONS: The erythematous form of candidiasis is often devoid of hyphae yet the presence of Candida antigens in the surface epithelium implicates an immune or allergic process . The intactness of chemokines and antimicrobial calprotectin in keratinocytes may explain why disseminated candidiasis is rarely encountered in HIV-infected patients.

Alcohol Clin Exp Res, 1997 Oct, 21(7), 1212 - 7
Ethanol feeding inhibits proinflammatory cytokine expression from murine alveolar macrophages ex vivo; Standiford TJ et al.; The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating and chemotactic cytokines . In this study, we assessed the effect of alcohol ingestion on the expression of tumor necrosis factor-alpha (TNF-alpha), and the chemokines macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) from murine alveolar macrophages (AMs) cultured ex vivo . Two-week ethanol feeding resulted in substantial impairment in the lipopolysaccharide (LPS)-induced expression of TNF-alpha, MIP-2, and MIP-1 alpha mRNA, and protein from LPS-stimulated AMs, compared with cytokine production from AMs obtained from CD-1 mice receiving an isocaloric control diet . These findings indicate that ethanol feeding results in diminished production of chemotactic and/or activating cytokines from AMs ex vivo that may contribute to the impairment in lung inflammatory responses and antimicrobial host defense that is observed in the setting of alcohol ingestion/intoxication clinically and experimentally.

Liver Transpl Surg, 1996 Jan, 2(1), 8 - 13
Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure; Rolando N et al.; The efficacy of prophylactic parenteral antibacterials, with or without selective decontamination of the digestive tract, was compared in patients with acute liver failure (ALF) or severe acetaminophen hepatotoxicity . One hundred eight patients were randomized on admission to receive intravenous ceftazidime and flucloxacillin, plus either oral and enteral decontamination with colistin, tobramycin, and amphotericin B (group 1), or enteral amphotericin B alone (group 2) . The two groups were comparable with respect to age, gender, etiology, coma grade on admission, international normalization ratio, presence of renal failure, Acute Physiology and Chronic Health Evaluation II score, and indicators of poor prognosis . Patients were monitored for clinical and microbiological evidence of infection . There were 15 episodes of infection in 10 of 47 patients (21%) in group 1 and 17 episodes in 12 of 61 patients (20%) in group 2 . No differences in incidence, site, and causative organisms of infection were observed between the two groups . Overall, the incidence of infection was significantly higher in patients who developed encephalopathy than in those who did not . In patients who on arrival were not encephalopathic, the development of infection was associated with progression to coma . Duration of Liver Intensive Care Unit (LICU) stay was an independent risk factor for the development of infection . Parenteral antibiotics are effective at reducing the risk of infection in patients with ALF; enteral decontamination provided no additional benefit.

Diagn Microbiol Infect Dis, 1997 Aug, 28(4), 221 - 3
Susceptibility of ninety-eight clinical isolates of Legionella to macrolides and quinolones using the Etest; Schrock J et al.; Isolates of Legionella from 98 patients with Legionnaires' disease hospitalized in Columbus, Ohio, USA between 1991 through 1995 were tested for antimicrobial susceptibility to macrolides and quinolones using the Etest . Most (87%) isolates were Legionella pneumophila serogroup 1 . All isolates tested remain susceptible to erythromycin, azithromycin, clarithromycin, ciprofloxacin, ofloxacin, and levofloxacin . In vitro susceptibility testing of Legionella to representative macrolides and quinolones should be considered to detect the emergence of resistant isolates.

FEBS Lett, 1997 Sep 22, 415(1), 64 - 6
Chemotherapeutic activity of synthetic antimicrobial peptides: correlation between chemotherapeutic activity and neutrophil-activating activity; Nakajima Y et al.; The chemotherapeutic activity of three synthetic antibacterial peptides was investigated . KLKLLLLLKLK-NH2 and its D-enantiomer showed significant chemotherapeutic activity in MRSA-infected mice, whereas KLKLLLKLK-NH2, which showed the highest antibacterial activity among them in vitro, was found to have almost no ability to prevent MRSA infection . These results suggest that the antibacterial activity of peptides assessed in vitro does not necessarily correlate with their chemotherapeutic activity . We found that KLKLLLLLKLK-NH2 and its D-enantiomer, but not KLKLLLKLK-NH2, have the ability to activate human neutrophils to produce superoxide, suggesting that the prevention of MRSA infection by these peptides is not simply due to their direct bactericidal activity but to augmentation of the systemic defense mechanism mediated by neutrophils.

Blood, 1997 Oct 1, 90(7), 2670 - 9
Dysregulation of membrane-bound tumor necrosis factor-alpha and tumor necrosis factor receptors on mononuclear cells in human immunodeficiency virus type 1 infection: low percentage of p75-tumor necrosis factor receptor positive cells in patients with advanced disease and high viral load; Hestdal K et al.; The correlation of persistent tumor necrosis factor-alpha (TNF-alpha) activation with disease progression in patients infected with human immunodeficiency virus type 1 (HIV-1), suggests a role for TNF-alpha in the pathogenesis of HIV-1 infection . In the present study, we examined by flow cytometry the expression of membrane-bound (m) components of the TNF system in 33 HIV-1-infected patients and 12 healthy controls . While peripheral blood mononuclear cells (PBMC) from asymptomatic and symptomatic non-acquired immune deficiency syndrome (AIDS) patients showed a significantly increased percentage of mTNF-alpha+ and mTNF receptor (TNFR)+ cells compared with controls, this was not found in the AIDS group . Compared with healthy controls, AIDS patients had a significantly decreased percentage of both monocytes and lymphocytes expressing p75-TNFR . PBMC from AIDS patients showed a higher p75-TNFR mRNA level and a higher spontaneous release of soluble p75-TNFR than healthy individuals, suggesting enhanced cell surface turnover of this TNFR . The low expression of TNFRs on both lymphocytes and monocytes in the AIDS group was associated with high numbers of HIV-1 RNA copies in plasma, low numbers of CD4+ lymphocytes, and high serum levels of soluble TNFRs . AIDS patients had a decreased percentage of CD8+ lymphocytes expressing TNFRs compared with healthy controls . In contrast, these patients, as well as symptomatic non-AIDS patients, had an increased percentage of TNF-alpha+ and TNFRs+ cells among remaining CD4+ lymphocytes . The pattern of abnormalities seen in AIDS patients suggests a role for persistent activation of the TNF system in the accelerated CD4+ lymphocyte destruction, the enhanced HIV-1 replication, and the markedly impaired antimicrobial defense in advanced HIV-1-related disease.

Eur J Clin Microbiol Infect Dis, 1997 Aug, 16(8), 568 - 74
Increasing incidence of nosocomial Chryseobacterium indologenes infections in Taiwan; Hsueh PR et al.; To understand the clinical features, antimicrobial therapy, and epidemiology of Chryseobacterium indologenes infections, the medical records of 36 patients with nosocomial Chryseobacterium indologenes infections seen over a three-year period at National Taiwan University Hospital were reviewed . The 36 isolates recovered from these patients were studied by molecular typing and determination of antimicrobial susceptibility patterns . Nine patients had underlying neoplastic diseases, seven had diabetes mellitus, five had burn wounds, and four had uremia . The clinical syndrome included ten patients with intraabdominal infections, nine with wound sepsis, six with intravascular catheter-related bacteremia, and four with ventilator-associated pneumonia . Thirteen patients had monomicrobial bacteremia, and four had polymicrobial bacteremia . Nineteen patients (53%) developed infections associated with various indwelling devices . The deaths of five patients (14%) were directly attributable to infection with Chryseobacterium indologenes . All isolates recovered showed a wide range of resistance to commonly used antimicrobial agents . The random amplified polymorphic DNA (RAPD) patterns of the isolates differed from each other, indicating the absence of epidemiological relatedness among these isolates . Nosocomial infection caused by multiresistant Chryseobacterium indologenes appears to be an emerging problem in Taiwan and should be studied further.

Equine Vet J, 1997 Sep, 29(5), 378 - 81
Pharmacokinetics of enrofloxacin in horses after single intravenous and intramuscular administration; Kaartinen L et al.; Pharmacokinetic behaviour of enrofloxacin was studied in 6 horses after intravenous (i.v.) or intramuscular (i.m.) administration of enrofloxacin (5 mg/kg bwt) . Concentration of enrofloxacin and ciproflaxin were measured by high performance liquid chromatography in serum . Antimicrobial activity of the samples was determined with an agar-diffusion technique . Reactions at the site of i.m . injection were monitored clinically and by determination of serum creatine kinase (CK) activity . After i.v . administration, elimination half-life of enrofloxacin was 4.4 h and volume of distribution was 2.3 1/kg bwt . Enrofloxacin was rapidly metabolised to ciprofloxacin . The half-life of ciprofloxacin parallelled that of the parent drug, its concentration in serum reached 20-35% of that of the parent drug . After i.m . administration, elimination half-life of enrofloxacin was longer (9.9 h) than after i.v . administration . Mean absorption time of enrofloxacin was also long (9.9 h) . No statistically significant differences were found when half-life and mean residence time of antimicrobial activity were compared with those of enrofloxacin and ciprofloxacin from chemically analysed data . Intramuscular injection of enrofloxacin was found to be very irritating . After i.m . administration, CK activity in serum, compared with pre-injection levels, increased over 10-fold . CK activity also stayed high during the 32 h follow-up period . Clinical reactions, such as swelling or tenderness at the i.m . injection sites, were observed in 2 horses.

Pharmacoeconomics, 1997 Dec, 12(6), 637 - 47
Assessing antibacterial pharmacoeconomics in the intensive care unit; Birmingham MC et al.; Intensive care units (ICUs) represent areas of high use of antibacterials and other pharmacy goods and services . Many institutions view their ICUs as a target for drug-use surveillance and cost-containment programmes . Economic assessment of antibacterial interventions in the ICU should include all direct costs and patient outcomes . Nonetheless, many of these institutions focus their efforts at reducing antibacterial costs without considering the consequences of these actions . It is possible that devoting more resources to antibacterials can have an overall positive economic impact if more appropriate antibacterial use reduces length of stay, decreases bacterial resistance or lowers frequency of adverse complications . Two consequences of antibacterial use which can result in substantial economic burdens to institutions are drug-induced complications (toxicities and adverse events) and the development of antibacterial-resistant organisms . These events are logical targets for performing pharmacoeconomic studies to evaluate appropriate and inappropriate antibacterial use . Either of these problems can increase length of stay, which is the single most important variable influencing the overall cost of patient care . The primary goal of patient care is to hasten patients' clinical improvement . This will result in decreased antibacterial acquisition costs, decreased lengths of ICU and hospital stays, and ultimately decreased consumption of hospital resources . These can be accomplished by using strategies to guide antibacterial use in order to reduce failures, adverse events, toxicity and antimicrobial resistance.

Am J Infect Control, 1997 Oct, 25(5), 387 - 9
Novel uses of the aromagram in infection control and epidemiology; Bauer J et al.; BACKGROUND: To facilitate the interpretation of data used in infection control and epidemiology, a novel data presentation format (the aromagram) has been developed and modified . METHODS: Aromagrams were developed with a personal computer-based graphics application . Aromagrams were based on antimicrobial susceptibility data from all specimen submitted to the University of California San Diego Medical Center's clinical microbiology laboratory between July 1992 and December 1994 . RESULTS: The aromagrams created displayed both bacterial species-specific and antimicrobial agent-specific susceptibilities . Additional modified aromagrams incorporated costs of antimicrobial agents and temporal trends in susceptibility of individual species to selected antibiotics . CONCLUSIONS: The aromagram is a unique format for data presentation that can be used to illustrate antimicrobial susceptibilities (specific to both organisms and antimicrobial agents), temporal trends in susceptibility data, and antimicrobial costs . Aromagrams may be used to display data useful to infection control and epidemiology professionals and to clinicians.

Planta Med, 1997 Oct, 63(5), 477 - 9
Composition and antimicrobial activity of the essential oil of Cistus creticus subsp . eriocephalus; Demetzos C et al.; The chemical composition of the essential oil of the leaves of Cistus creticus subsp . eriocephalus (Viv.) Greuter & Burdet, (Cistaceae), was investigated by GC/MS . Thirty-nine components were identified, representing 73.9% (based on % total peak area by GC) of the oil composition . The main components of the oil were alpha-cadinene (6.5%), delta-cadinene (5.6%), viridiflorol (5.4%), bulnesol (6.3%), ledol (3.8%), alpha-copaene (3.8%), beta-selinene (3.4%), cubenene (3.3%), manoyl oxide (9.9%) and 13-epi-manoyl oxide (3.4%) . Antibacterial studies were carried out in vitro against Gram-positive and Gram-negative organisms.

Proc Natl Acad Sci U S A, 1997 Oct 28, 94(22), 12106 - 11
Evaluating treatment protocols to prevent antibiotic resistance; Bonhoeffer S et al.; The spread of bacteria resistant to antimicrobial agents calls for population-wide treatment strategies to delay or reverse the trend toward antibiotic resistance . Here we propose new criteria for the evaluation of the population-wide effects of treatment protocols for directly transmitted bacterial infections and discuss different usage patterns for single and multiple antibiotic therapy . A mathematical model suggests that the long-term benefit of single drug treatment from introduction of the antibiotic until a high frequency of resistance precludes its use is almost independent of the pattern of antibiotic use . When more than one antibiotic is employed, sequential use of different antibiotics in the population ("cycling") is always inferior to treatment strategies where, at any given time, equal fractions of the population receive different antibiotics . However, treatment of all patients with a combination of antibiotics is in most cases the optimal treatment strategy.

Eur J Biochem, 1997 Sep 15, 248(3), 938 - 46
Structural aspects of the interaction of peptidyl-glycylleucine-carboxyamide, a highly potent antimicrobial peptide from frog skin, with lipids; Latal A et al.; The interaction of PGLa (peptidyl-glycylleucine-carboxyamide), a 21-amino-acid residue cationic peptide, isolated from the skin of the South African clawed frog, Xenopus laevis, with model membrane systems was investigated . Our studies focussed on the importance of the difference in the phospholipid composition of bacterial and erythrocyte membranes . This is of particular interest to gain information on the specificity of membranolysis exhibited by this peptide against bacteria but not against erythrocytes . In phosphate buffer at physiological pH, as well as in the presence of the zwitterionic phosphatidylcholine and sphingomyelin . the peptide had a random structure but it adopted an alpha-helical conformation in the presence of negatively charged lipids . Furthermore, calorimetric experiments showed that PGLa had no effects on the thermotropic phase behavior of liposomes composed of the choline phosphatides, while separation of a distinct peptide-rich domain was observed for phosphatidylglycerol liposomes . In addition to the main transition of pure 1,2-dipalmitoylglycerophosphoglycerol at 40 degrees C a second transition owing to the peptide-perturbed lipid domains was found at 41 degrees C . This conclusion is supported by X-ray diffraction experiments which indicated that PGLa penetrates into the hydrophobic core of the bilayer inducing an untilting of the hydrocarbon chains as observed in the gel phase of the pure lipid . These results demonstrate that this antibacterial peptide specifically interacts with negatively charged lipid membranes, which are characteristic of bacterial membranes . This can be explained based on the structural features of PGLa.

Kansenshogaku Zasshi, 1997 Sep, 71(9), 910 - 7
{Effects of various steroidal and non-steroidal anti-inflammatory drugs on in-vitro IL-10 production of murine peritoneal macrophages infected with Mycobacterium avium complex}; Shimizu T et al.; In murine infections due to Mycobacterium avium complex (MAC), bacterial regrowth of the pathogens is frequently encountered in the relatively late phase of infection even in mice receiving daily treatments with antimicrobial agents including rifamycins and macrolides . In this case, the bacterial regrowth is usually accompanied by concomitant increase in the tissue levels of IL-10 and transforming growth factor-beta (TGF-beta), well known immunosuppressive cytokines . In this context, it is of interest to note recent findings that steroidal anti-inflammatory drugs up-regulate TGF-beta production from T lymphocytes, thereby suggesting participation of immunosuppressive cytokines in the expression of their anti-inflammatory activity . In this study, we examined the effects of various anti-inflammatory drugs including glucocorticoids and non-steroidal anti-inflammatory drugs (NSAID) on in-vitro IL-10 production of murine peritoneal macrophages (M phi s) infected with MAC organisms . When the IL-10 production by MAC-infected M phi s was measured in terms of protein and mRNA expression of the cytokine using ELISA and RT-PCR assays, the following results were obtained . First, the IL-10 production into M phi culture fluids was temporarily increased around days 1 to 3, thereafter gradually declined, and returned to normal by day 14 . Secondly, IL-10 mRNA expression of M phi s was rapidly induced after MAC-infection and the maximum level of the mRNA expression was achieved at 2 hr . Thereafter, IL-10 mRNA expression ceased rapidly and returned to normal by 24 hr . Thirdly, the majority of test anti-inflammatory drugs, not only glucocorticoids but also NSAID, were found to up-regulate the IL-10 production of MAC-infected M phi s, suggesting some possible roles of IL-10 in the expression of the anti-inflammatory activities of these agents.

Environ Res, 1997, 74(1), 84 - 90
Effect of in vitro exposure to tributyltin on generation of oxygen metabolites by oyster hemocytes; Anderson RS et al.; Mollusks depend chiefly on hemocyte-mediated cytotoxic mechanisms such as reactive oxygen species (ROS) to defend against pathogenic microorganisms . The effect of in vitro tributyltin chloride (TBT) exposure on ROS generation by oyster (Crassostrea virginica) blood phagocytes is quantified in this study . Luminol-augmented chemiluminescence (LCL) was used to measure ROS activity of resting and zymosan-stimulated cells after 1 or 20 hr TBT exposure . LCL is thought to measure primarily the activity of the myeloperoxidase/hydrogen peroxide/ halide antimicrobial pathway . Hemocytes in TBT-free medium (controls) produced low level LCL, which was markedly stimulated by the addition of zymosan particles . Both resting and zymosan-stimulated LCL values were significantly inhibited by > or = 80 ppb TBT after either 1 or 20 hr of exposure . Exposure to < or = 2 ppb TBT concentrations for 20 hr produced slightly enhanced LCL activity, suggesting a hormesis-like effect . Partial reversibility of TBT suppression of LCL took place when previously exposed cells were put in TBT-free medium . The TBT concentrations used in these studies were not cytolethal in vitro and were considerably less than oyster tissue levels recorded after chronic, sublethal in vitro exposures . The data suggest that the common aquatic contaminant TBT can interact rapidly with C . virginica hemocytes to produce a partially reversible immunotoxicological lesion . Xenobiotic-induced suppression of ROS production by hemocytes may increase host susceptibility to infectious diseases.

Rev Rhum Engl Ed, 1997 Jul-Sep, 64(7-9), 474 - 80
Do minocycline and other tetracyclines have a place in rheumatology?
Toussirot E, Despaux J, Wendling D.
Tetracyclines are a family of antimicrobials with activity against a broad range of organisms including those that develop intracellularly . Links have been reported between some infections and some inflammatory joint diseases, with the most notable example involving mycoplasmas and rheumatoid arthritis . Reactive arthritides are known to be triggered by organisms found in the gastrointestinal or genitourinary tract, and antigenic material from these organisms has recently been demonstrated in synovial tissue from patients with reactive arthritis . These facts led to the hypothesis that tetracyclines may be useful in rheumatoid arthritis and reactive arthritis . Two controlled studies found that minocycline benefited rheumatoid arthritis patients when it was given either as an adjunct to another second-line treatment or as the only slow-acting drug . Lymecycline has been found to expedite recovery from reactive arthritis due to Chlamydia trachomatis, and tetracycline to decrease the incidence of reactive arthritis due to sexually-transmitted diseases . The safety profiles of these treatments were acceptable in all available studies but require further investigation during long-term administration . The benefits may be related to the immunomodulating effects of tetracyclines and/or to their ability to inhibit metalloproteases such as collagenases . Whether tetracycline therapy influences the course of radiologic lesions in rheumatoid arthritis remains unknown . However, minocycline therapy has given sufficient proof of its efficacy to make it an attractive alternative in rheumatoid arthritis.

J Bacteriol, 1997 Oct, 179(19), 6163 - 71
Characterization of a locus from Carnobacterium piscicola LV17B involved in bacteriocin production and immunity: evidence for global inducer-mediated transcriptional regulation; Quadri LE et al.; Mutational, nucleotide sequence, and transcriptional analyses of a 10-kb fragment (carnobacteriocin locus) from the 61-kb plasmid of Carnobacterium piscicola LV17B demonstrated the presence of two gene clusters (cbnXY and cbnSKRTD) upstream of the previously sequenced carnobacteriocin B2 structural and immunity genes (cbnB2 and cbiB2) . Deduced products of cbnK and cbnR have sequence similarity to proteins of Agr-type two-component signal transduction systems, and those of cbnT and cbnD have sequence similarity to proteins of signal sequence-independent secretion systems . Deduced products of cbnX, cbnY, and cbnS are class II-type bacteriocin precursors with potential leader peptides containing double-glycine cleavage sites . Genetic analysis indicated that the 10-kb locus contains information required for the production of, and immunity to, the plasmid-encoded carnobacteriocin B2 and the chromosomally encoded carnobacteriocin BM1 . In addition, this locus is involved in the production of at least one additional antimicrobial compound and an inducer factor that plays a role in the regulation of carnobacteriocin B2 . Transcription analysis indicated that the operons cbnXY, cbnB2-cbiB2, and cbnBM1-cbiBM1 (with the latter encoding carnobacteriocin BM1 and its immunity protein on the chromosome) and two small transcripts containing cbnS are transcribed only in induced cultures . These transcripts are coregulated and subject to inducer-mediated transcriptional control . Similar regulation of the cbn operons is mirrored by the similarity in the nucleotide sequence of their promoter regions, all of which contain two imperfect direct repeats resembling those in Agr-like regulated promoters upstream of the transcription start sites.

Am J Surg, 1997 Sep, 174(3), 284 - 90
Meta-analysis of the clinical outcome of carbapenem monotherapy in the adjunctive treatment of intra-abdominal infections; Chang DC et al.; BACKGROUND: The carbapenems, a class of beta-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections . Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy . We report here a meta-analysis of 10 such trials . DATA SOURCES: An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects . Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients . A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens . We found a difference in response rates of -1.6% (95% confidence interval {CI} -5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference . CONCLUSIONS: A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections . We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications . This may have been due to the selection of less effective comparators in earlier studies . We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.

Int J Pediatr Otorhinolaryngol, 1997 Aug 20, 41(2), 145 - 54
Decreasing morbidity following laryngotracheal reconstruction in children; Yellon RF et al.; Our objectives are to report (1) methods for decreasing infectious complications and excessive weakness associated with the period of sedation and neuromuscular blockade (NMB) following single-stage laryngotracheal reconstruction (SSLTR); (2) an association between gastroesophageal reflux (GER) and subglottic stenosis (SGS); (3) results of 21 SSLTRs and 15 two-stage LTRs (TSLTRs) . A retrospective chart review was performed for the period January, 1990-August, 1995, including 36 patients who had 38 LTRs for SGS and/or posterior glottic stenosis at a tertiary care center . Our most recent post-SSLTR protocol included: (1) prophylactic antimicrobials (clindamycin plus antipseudomonal agents = C + A); (2) GER treatment; (3) titrated infusion NMB with daily recovery of neuromuscular function; (4) avoidance of prolonged simultaneous administration of NMB and corticosteroids . Patients who had prophylactic antimicrobials (C + A) during intubation following SSLTR had fewer (1/13, 8%) postoperative infectious complications than patients who received other/no antibiotics (4/8, 50%) (P < 0.05) . Avoidance of prolonged simultaneous administration of NMB and corticosteroids and use of titrated infusion of NMB with daily recovery of neuromuscular function was associated with less weakness following extubation (0/11, 0% vs . 4/6, 66%) (P < 0.002) . Of 26 patients tested for GER, 21 (81%) had at least one positive test, suggesting a significant association between GER and SGS (P < 0.05) . The overall success rate for LTR was 33/36 or 92% . SSLTR had a 95% success rate while two-stage LTR had an 87% success rate, although two revisions were required . Prophylactic antimicrobials, improved postoperative management and GER treatment allowed successful LTRs with decreased infectious complications and less weakness.

J Antimicrob Chemother, 1997 Sep, 40(3), 319 - 27
The potential management of resistant infections with non-antibiotics; Kristiansen JE et al.; The antimicrobial activity of synthetic, non-chemotherapeutic compounds, such as the phenothiazine, methylene blue, has been known since the time of Ehrlich (1854-1915) . In this context the term 'non-antibiotics' is taken to include a variety of compounds which are employed in the management of pathological conditions of a non-infectious aetiology, but which modify cell permeability and have been shown to exhibit broad-spectrum antimicrobial activity . The antimicrobial properties of compounds such as phenothiazines, as well as those of other neurotropic compounds, have only been investigated sporadically, and their application to management of microbial infections has not been evaluated . A review of the literature, coupled with a number of more recent investigations, suggests that some of these and other membrane-active compounds enhance the activity of conventional antibiotics, eliminate natural resistance to specific antibiotics (reversal of resistance) and exhibit strong activity against multi-drug resistant forms of Mycobacterium tuberculosis . Thus non-antibiotics may have a significant role in the management of certain bacterial infections.

Clin Infect Dis, 1997 Aug, 25(2), 230 - 9
Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes; White AC Jr et al.; Antimicrobial control programs are widely used to decrease drug expenditures, but effects on antimicrobial resistance and outcomes for patients are unknown . When a requirement for prior authorization for selected parenteral antimicrobial agents was initiated at our urban, county teaching hospital, total parenteral antimicrobial expenditures decreased by 32% . Susceptibilities to all beta-lactam and quinolone antibiotics increased, with dramatic increased susceptibilities in isolates recovered in intensive care units, increased susceptibilities in isolates recovered in other inpatient sites, and little change in susceptibilities in isolates recovered in outpatient sites despite no change in infection control practices . For patients with bacteremia due to gram-negative organisms, overall survival did not change with restrictions . No differences occurred in the median time from initial positive blood culture to receipt of an appropriate antibiotic or in the median time from positive blood culture to discharge from the hospital . Thus, requiring preapproval for selected parenteral agents can decrease antimicrobial expenditures and improve susceptibilities to antibiotics without compromising patient outcomes or length of hospital stay.

Clin Cardiol, 1997 Oct, 20(10), 885 - 8
Coronary embolism complicating aortic valve endocarditis: treatment with placement of an intracoronary stent; Glazier JJ et al.; A 37-year-old man, who had received 3 weeks of antimicrobial therapy for aortic value endocarditis, presented with an acute anteroseptal wall myocardial infarction . Coronary angiography demonstrated occlusion of the mid left anterior descending artery, thought to have been caused by embolization of a sterile vegetation . Following failure of balloon dilation to achieve vessel patency, this was achieved by placement of an intracoronary stent.

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