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 g