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This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia.
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In total, 335/360 patients completed the study (93.1%). Seven patients receiving gemifloxacin withdrew from the study compared to 18 patients receiving levofloxacin; this difference was statistically significant (Fisher's exact test: p=0.02). In the intent-to-treat (ITT) population, the clinical success rate at follow-up (Days 14-21) was 85.2% (155/182) with gemifloxacin and 78.1% (139/178) with levofloxacin. Clinical success rate in the per-protocol (PP) population was 88.2% (134/152) with gemifloxacin and 85.1% (126/148) with levofloxacin. At long-term follow-up (Days 28-35), the clinical success rates in the PP population were 83.7% (123/147) with gemifloxacin and 78.4% (109/139) with levofloxacin. The difference in success rates was 5.26% (95% CI: -3.83, 14.34).
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The main objective of the current study was to estimate the potential environmental risks associated with human consumption of antimicrobials in Greece. Consumption data was collected for the 24 most often used antimicrobials for the years 2008-2010, and their predicted environmental concentrations (PECs) in raw and treated wastewater were calculated using mass balances and literature data on human excretion and elimination efficiency during wastewater treatment. The ecotoxicological risk was estimated by calculating the ratio of PEC to predicted no-effect concentration (PNEC) for three categories of aquatic organisms (algae, daphnids, and fish). PNEC values were calculated based on experimental ecotoxicity data and data originated from the Ecological Structure Activity Relationship (ECOSAR). PEC values in raw sewage ranged between 0.02 μg L(-1) (erythromycin) and 27 μg L(-1) (amoxicillin), while in treated wastewater, the highest concentration was predicted for cefuroxime axetil (6.6 μg L(-1)). Based on acute toxicity data for algae, risk quotient (RQ) values higher than 1 were obtained for 7 out of the 24 target antimicrobials in raw and treated wastewater, while no significant risk was estimated for daphnids and fish. Regarding the possible risk due to the chronic toxicity of antimicrobials, RQ values higher than 80 were obtained for amoxicillin and clarithromycin in algae. The use of baseline toxicity data from ECOSAR showed that the environmental risk from exposure to mixtures of antimicrobials was low for all three aquatic species. However, further studies on toxicity of mixtures should be performed as calculation of toxicity ratio (TR) values showed that 90 % of the target antimicrobials seem to exhibit a specific mode of toxic action when present in mixtures rather than baseline toxicity. As a result, an underestimation of toxicity based on the ECOSAR model is possible for the mixture of target antimicrobials. For Greek rivers where low (dilution factor, D<10) and medium (D=10-100) dilution of wastewater occurs, moderate to high risk is expected due to the existence of individual antimicrobials such as amoxicillin, clarithromycin, ciprofloxacin, azithromycin, erythromycin, and levofloxacin in discharged treated wastewater.
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Globally, the incidence of urinary tract infections during 15 days after surgery was 8.4% (11 cases out of 131): ciprofloxacin 9.1%, levofloxacin 11.1% and prulifloxacin 5.5%, respectively. The patients compliance with the prophylactic treatment was good or excellent in 122 cases (93.1%) and poor in 9 cases (6.9%). No major differences between antibiotics used in prophylaxis were detected, keeping into account the limited size of the global population and subgroups defined by the endourological procedures.
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Serum samples of 13 patients with multidrug-resistant tuberculosis were taken 0, 1, 2, 4, 8 h after administration of antimycobacterial drugs for assay of levels in order to gain further insight into their basic pharmacokinetics. The drugs assessed were amikacin, kanamycin, ofloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, cycloserine, pyrazinamide and ethambutol. Techniques used for assay were reversephase high-performance liquid chromatography, gas liquid chromatography and fluorescent polarization immunoassay. The results from 12 patients were evaluated. These provided new pharmacokinetic data on high-dose levofloxacin, cycloserine and prothionamide given once daily, and could be useful in guiding the scheduling of drugs. The data obtained might also lead to insights into the development of therapeutic drug monitoring in multidrug-resistant tuberculosis.
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Records of 97 men and 69 women aged 13 to 85 (mean, 50) years who underwent treatment for suspected M marinum tenosynovitis of the hand and wrist were retrospectively reviewed. All underwent open biopsy; synovectomy was performed when florid synovitis was present. Rifampicin and ethambutol were usually prescribed. Clarithromycin, minocycline and/or levofloxacin were used as adjuvants if there was drug intolerance, allergy, or relapse. The duration of antibiotic treatment depended on the clinical recovery. Patients were followed up for one year after completion of drug treatment. Functional outcome was considered excellent for those with >195º total active motion (TAM) and >75% return of motion, good for those with 130º to 195º TAM and 50 to 75% return of motion, fair for those with 65º to 129º TAM and 25 to 49% return of motion, and poor for those with<65º TAM and <25% return of motion.
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In vitro determination of Clostridium difficile susceptibility to antibiotics is not routinely performed. The aim of this study was to evaluate the performance of antibiotic susceptibility determination with the disk diffusion method for screening C. difficile isolates with decreased susceptibility to antibiotics.
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Klebsiella pneumoniae, Escherichia coli and Staphylococcus epidermidis are major pathogens of nosocomial infections in neonates in the NICU and they are resistant to β-lactam antibiotics. Mechanical ventilation and hospitalization time are the most important risk factors for nosocomial infections caused by Klebsiella pneumoniae and Escherichia coli respectively.
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Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy.
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Levofloxacin-based and sequential therapy are superior to standard triple scheme as first-line regimens in a setting with high clarithromycin resistance. However, all of these therapies still have a 20% failure rate.