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At T0, 53 out of 89 patients (60%) in the control and 48 out of 70 patients (69%) in the study group harbored coagulase-negative Staphylococcus. Among these coagulase-negative Staphylococcus, 12 out of 53 in the control and 11 out of 48 in the study group were resistant to ofloxacin (p>0.9999). At T1, significantly fewer coagulase-negative Staphylococcus (p=0.0003) were isolated from the study group (18 coagulase-negative Staphylococcus), compared the control group (48 coagulase-negative Staphylococcus). Of these, 5 out of 17 coagulase-negative Staphylococcus in the study group and 9 out of 48 coagulase-negative Staphylococcus in the control group were resistant to ofloxacin (p=0.5649). There was no significant difference in the number of coagulase-negative Staphylococcus resistant to ciprofloxacin or norfloxacin in the study group compared to the control group at T1.
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Pescaprein XVIII (1), a type of bacterial efflux pump inhibitor, was obtained from the CHCl(3)-soluble resin glycosides of beach morning glory (Ipomoea pes-caprae). The glycosidation sequence for pescaproside C, the glycosidic acid core of the lipophilic macrolactone 1 containing D-xylose and L-rhamnose, was characterized by means of several NMR techniques and FAB mass spectrometry. Recycling HPLC also yielded eight non-cytotoxic bacterial resistance modifiers, the two pescapreins XIX (2) and XX (3) as well as the known murucoidin VI (4), pecapreins II (6) and III (7), and stoloniferins III (5), IX (8) and X (9), all of which contain simonic acid B as their oligosaccharide core. Compounds 1-9 were tested for in vitro antibacterial and resistance-modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. All of the pescapreins potentiated the action of norfloxacin against the NorA over-expressing strain by 4-fold (8 microg/mL from 32 microg/mL) at a concentration of 25 microg/mL.
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Six patients with acute peritonitis undergoing continuous ambulatory peritoneal dialysis for end-stage renal failure received an 800 mg loading dose of pefloxacin mesylate orally followed by 400 mg twice daily orally for 10 or 21 days. Plasma and dialysate levels of both pefloxacin and its metabolites were measured. Plasma levels in excess of the MIC for all infective bacteria were achieved within 90 min and in dialysate within 4 h. No significant accumulation of pefloxacin or its metabolite norfloxacin was noted. However, both serum and dialysate levels of the metabolite pefloxacin N-oxide rose continuously during treatment. Plasma and dialysate levels of all three agents fell rapidly during the five days after treatment had stopped. No major side effects were observed, although two patients developed Achilles tendonitis.
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The prevalence of antimicrobial resistance among urinary pathogens has been increasing worldwide. Laboratory diagnosed urinary tract infections were retrospectively evaluated for the years 1996 through 1999, to document the common pathogens and their changing antimicrobial profiles. From 14,853 hospital specimens, an isolation rate of 6.1% was found; and from 5330 community specimens, the isolation rate was 27.9%. E. coli was the predominant cause of urinary tract infections in both hospital and community practices. The rate of isolation of the other pathogens was relatively stable except for citrobacter species, which increased from 1.3% in 1996 to 20.1% in 1999 (p < 0.001) among community isolates. Significant changes in the susceptibility patterns of uropathogens also were observed. E. coli strains from hospitals were significantly more resistant to cefuroxime than community strains (p < 0.001), while resistance to ampicillin and nalidixic acid was high in both practices. No substantial changes in susceptibility to gentamicin and tetracycline were noticed during the four-year period compared to the 99% resistance to tetracycline in 1995. In relation to nitrofurantoin, no significant changes were noted in both practices where resistant rates remained low, but susceptibility to augmentin showed much improvement among all isolates, including E. coli. Urinary isolates were more commonly recovered from the paediatric age group (1-10 years) and those older than 50 years of age, and males were the predominant gender in both age groups. The study showed that the antibiotics useful in the treatment of UTI in decreasing order of effectiveness in community practice were gentamicin, norfloxacin, nitrofurantoin and cefuroxime. For nosocomial UTI, the drugs most effective include norfloxacin, nitrofurantoin, gentamicin, co-trimoxazole and amoxicillin-clavulanic acid.
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Acute hemorrhage from esophageal varices due to portal hypertension is a frequent and serious complication of liver cirrhosis. Bacterial infection may be one of the factors influencing such hemorrhage. Endotoxins may increase portal tension and at the same time result in primary hemostasis disorder, thus becoming one of the causes of hemorrhage. The authors of the paper compared the incidence of bacterial infection in 53 patients with varicose hemorrhage due to portal hypertension with 62 patients with liver cirrhosis and portal hypertension without varicose hemorrhage. At least one pathogen was found in considerable 61.1% of the total of patients in the liver cirrhosis group, while the difference between the two groups was but insignificant. No statistically significant difference was found between the group of patients with hemorrhage and those without hemorrhage in terms of presence of bacterial infection in hemoculture, urine, throat, faeces and ascites, nor was there a difference in the etiology of the G+ bacteria, G- bacteria or fungi and yeast infectious agents in the hemoculture, urine, throat, faeces and ascites in either of the groups. No statistically significant difference was found in comparing the patients with a recurrence of hemorrhage (or with mortality) and with infection with those without recurrence of hemorrhage. Bacterial infection was more often found in patients with a recurrence of hemorrhage (75%) as compared with those without any recurrence (52%), and also in patients who died bacterial infection was proven more often than in those who survived (61.9% vs. 58.1%, respectively). There was no difference in morbidity or recurrence of hemorrhage between the patients treated with norfloxacin and ampicilin/sulbactam. No statistically significant difference was recorded between the 1st and 5th day in terms of decrease in bacterial infection. A significant difference was found in the urine etiological agent, where a significant increase in the share of fungal and yeast urine infection (p = 0.011) was recorded after the application of the therapy, as well as a drop in urine infection caused by the G- bacterial agent (p = 0.057).
Over a period of 10 years, 75 issues of a drug bulletin (2000 copies) were distributed. Oral producer-independent drug information, provided jointly by a GP and a pharmacist, was given on 16 occasions in each of 30 health centres (150 GPs). Around 80% of the GPs participated in the meetings. Of these GPs, 75% found the service important for their daily work. A majority of the GPs had prescribed the test drug, norfloxacin, not a first-line drug according to local recommendations, 1 year after approval. A significantly lower proportion of prescribers were observed in the area where the GPs had been provided with both written and oral information regarding recommended treatment (including first-line drugs) for uncomplicated cystitis. The approximate cost for this service in 1995 was SEK 0.685 million (USD 0.1 million); the prescribing costs of the 150 GPs were estimated at SEK 255 million per year. This means that the cost of the service per GP is only around 0.3% of normal prescribing costs.
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The in-vitro activity of ciprofloxacin, a new quinolone derivative, was determined by broth microdilution for 518 clinical isolates. The MICs for 90% of the organisms were 2 mg/l for Pseudomonas aeruginosa, 8 mg/l for P. maltophilia, 4 mg/l for other Pseudomonas spp., 1 mg/l for Acinetobacter anitratus, 0.03-0.5 mg/l for differing species of Enterobacteriaceae, 2 mg/l for Streptococcus faecalis, 0.25 mg/l for coagulase-negative Staphylococcus spp. and 2 mg/l for S. aureus. Furthermore, on a weight basis, the activity of ciprofloxacin was equivalent or superior to that of cefotaxime, ceftazidime, gentamicin, imipenem, latamoxef, piperacillin, oxacillin and vancomycin. In general, ciprofloxacin appears to be highly active against organisms resistant to many broad spectrum antimicrobials, including norfloxacin, gentamicin, cefotaxime, and ceftazidime, with MICs for 90% of organisms in the range of 0.03 to 16 mg/l.
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Acute gastroenteritis is a potential cause of substantial morbidity in U.S. military personnel during deployment. This study investigated the microbial causes of diarrhea in U.S. troops on exercises in Southeast Asia aboard the U.S.S. Germantown from March through May 1996. A total of 49 (7%) patients with diarrhea reported to sick call during a 3-month deployment involving 721 personnel. Diarrheal samples from 49 patients were subjected to bacterial and parasitologic examination, but sufficient samples from only 47 of 49 were available for analysis of the presence of Norwalk-like virus (NLV). Of the 49 diarrhea cases, 10 (20.4%) appeared to be due to bacterial etiology alone, 10 (20.4%) due to bacteria and the prototype Taunton agent (TNA), 11 (22.4%) due to TNA only, and 4 (8.0%) due to parasites. Norwalk-like virus RNA was present in 21 (45%) of 47 stool samples from the diarrhea cases, 10 with bacterial etiologies and 11 without bacterial or parasitic etiologies. No pathogen was detected in 14 (29%) of the cases. Four of the controls showed the presence of parasitic organisms. Of the 11 cases in which enterotoxigenic Escherichia coli was isolated, 8 were positive for colonization factor antigen (CFA/IV), and 3 were CFA-negative. The bacterial pathogens tested were all susceptible to gentamicin, and furadantin, but were resistant to ceftriaxone and norfloxacin, including 75% of the Campylobacter spp. These data support the view that the major cause of diarrhea for troops deployed in this geographic area is most likely NLVs.
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An outbreak of salmonellosis was recorded in captive pygmy hogs (Sus salvanius), a critically endangered species of mammal. Of 42 captive animals maintained for conservation breeding by the Pygmy Hog Conservation Programme, Guwahati, Assam, India, 7 (16.67%) died within 3 days. The organism associated with this outbreak was identified as Salmonella enteritidis. The organisms were highly susceptible to chloramphenicol, gentamicin, norfloxacin and cefotaxim but were resistant to ampicillin, oxytetracycline, mezlocillin and sulfamerazin. The strain belonged to phage type 13a/7 and harboured two plasmids (38 and 44 megadaltons). The organisms were enterotoxigenic in CHO cell assay and were found to carry stn, sef and pef genes.
Quinolones are widely used, broad-spectrum antimicrobial agents. In screens for genes that, when overexpressed, allow Escherichia coli to grow on otherwise lethal concentrations of the fluoroquinolone norfloxacin, the ydhE gene was identified. We have shown that ydhE encodes a multidrug efflux pump with a narrower substrate range than that of its closest homologue, encoded by norM, and named the gene norE. The relative contributions to drug resistance of NorE compared with the two other known E. coli quinolone pumps, AcrAB and MdfA, have been defined. Overexpression of each of the three pumps separately resulted in roughly similar levels of quinolone resistance, whereas simultaneous overexpression of norE or mdfA in combination with acrAB gave synergic increases in quinolone resistance. The level of quinolone resistance mediated by efflux pumps seems to be constrained to an approximately 10-fold maximum, even with increased production of the pumps. We measured the drug resistance of an isogenic set of strains containing the various permutations of single, double and triple drug efflux pump mutants. The DeltanorE and DeltamdfA mutants were somewhat more susceptible to fluoroquinolones than the parent strain, and acrAB mutants were four- to six-fold more susceptible. Mutants lacking two or all three efflux pumps were not significantly more susceptible to fluoroquinolones than those lacking only one of the three pumps.
Many different drug-resistant lines of rodent malaria are available as screening models. It is obligatory to screen new compounds for antimalarial activity against a series of resistant lines in order to identify a compound with potential for the treatment of multi-drug resistant (MDR) malaria infections. Instead of using a battery of resistant lines, a single MDR Plasmodium yoelii nigeriensis strain that shows a wide spectrum of drug resistance to high doses of chloroquine, mepacrine, amodiaquine, mefloquine, quinine, quinidine, halofantrine as well as tetracyclines, fluoroquinolines and erythromycin, was used to assess the blood schizontocidal efficacy of a new macrolide azithromycin and other antibiotics. The present study shows that only azithromycin has the potential to control an MDR P. y. nigeriensis infection in Swiss mice, provided the treatment with a dose of 50-100 mg/kg/day by oral route is continued for a period of 7 days. Tetracycline, oxytetracycline, doxycyline, erythromycin, ciprofloxacin and norfloxacin, although active in vitro, failed to protect the mice. Tetracycline, ciprofloxacin and norfloxacin combinations with chloroquine did not control the infection. Additionally, the antimalarial efficacy of azithromycin can be potentiated with the addition of arteether, which is an ethyl ether derivative of artemisinin. A total (100%) curative effect has been obtained with a shorter regimen of 4 days only.