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The present study was carried out to assess comparatively the effectiveness and tolerance of norfloxacin, enoxacin and ofloxacin in the treatment and prophylaxis of infections of the low urinary tract in non-hospitalised patients. Thirty patients presenting positive uroculture on clinical evidence of ongoing infection were treated. Doses were 400 mg b.i.d. for norfloxacin, and 300 mg b.i.d. for ofloxacin and enoxacin; duration of treatment was 7 days in treatment. The pathogen was eradicated in 94% of cases at the control carried out after 5 days from the end of treatment; in the follow-up at 20 days, recurrences or reinfections were observed in 30% of the cases, almost all of them consisting of complicated infections. Slight side-effects were observed in 8 patients. No significant differences in effectiveness or tolerance were reported between the 3 quinolones under study which are therefore considered reliable overall for urological treatment. The absence of greater side-effects is related to the restriction of indications and the brevity of the therapeutic cycles.
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An efficient procedure for the simultaneous extraction and analysis of six fluoroquinolone (FQ) antibiotics is developed using an automated microdialysis-liquid chromatographic (LC) system. In this method, samples extracted from chicken liver and muscle are further purified by microdialysis, separated on an LC column, and the FQs detected by their fluorescence. Recoveries from fortified chicken liver and muscle samples are at least 70% with limits of quantitation (microg/kg) for the FQs in liver (and muscle) as follows: 0.3 (0.4) for danofloxacin, 0.8 (0.2) for desethylene ciprofloxacin, 2 (1) for norfloxacin, 2 (0.8) for enrofloxacin, 3 (1) for ciprofloxacin, and 5 (2) for sarafloxacin. Enrofloxacin and ciprofloxacin are determined in enrofloxacin-incurred chicken liver and muscle samples using this method.
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The dif locus is a site-specific recombination site located within the terminus region of the chromosome of Escherichia coli. Recombination at dif resolves circular dimer chromosomes to monomers, and this recombination requires the XerC, XerD and FtsK proteins, as well as cell division. In order to characterize other enzymes that interact at dif, we tested whether quinolone-induced cleavage occurs at this site. Quinolone drugs, such as norfloxacin, inhibit the type 2 topoisomerases, DNA gyrase and topoisomerase IV, and can cleave DNA at sites where these enzymes interact with the chromosome. Using strains in which either DNA gyrase or topoisomerase IV, or both, were resistant to norfloxacin, we determined that specific interactions between dif and topoisomerase IV caused cleavage at that site. This interaction required XerC and XerD, but did not require the C-terminal region of FtsK or cell division.
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Recent studies posit that reactive oxygen species (ROS) contribute to the cell lethality of bactericidal antibiotics. However, this conjecture has been challenged and remains controversial. To resolve this controversy, we adopted a strategy that involves DNA polymerase IV (PolIV). The nucleotide pool of the cell gets oxidized by ROS and PolIV incorporates the damaged nucleotides (especially 8oxodGTP) into the genome, which results in death of the bacteria. By using a combination of structural and biochemical tools coupled with growth assays, it was shown that selective perturbation of the 8oxodGTP incorporation activity of PolIV results in considerable enhancement of the survival of bacteria in the presence of the norfloxacin antibiotic. Our studies therefore indicate that ROS induced in bacteria by the presence of antibiotics in the environment contribute significantly to cell lethality.
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The post-antibiotic effect (PAE) is defined as the bacterial growth suppression which persists after a limited exposure to an antimicrobial agent. The PAE and the bactericidal effect of the quinolones ciprofloxacin, norfloxacin and nalidixic acid have been studied against several urinary isolates of Gram-negative bacteria. The PAE was determined after one hour's exposure to the antimicrobial agent using an initial inoculum of 10(5) to 10(6) cfu/ml; the drug was rapidly removed by a 10(-2) dilution technique in antibiotic-free medium. When ciprofloxacin was used at four times its MIC the PAEs were 1.37 +/- 0.09; 2.45 +/- 0.63 and 2.86 +/- 0.15 h against Esch. coli, Klebs. pneumoniae and Pseudomonas aeruginosa, respectively. We found lower values for norfloxacin under the same conditions, and nalidixic acid did not induce a significative PAE. These results could support changes in dosing intervals of norfloxacin and ciprofloxacin, with possibly greater intervals between doses.
Four newer quinolones (amifloxacin, ciprofloxacin, enoxacin, norfloxacin) were administered to female dogs by intravenous infusion. Drug concentrations in plasma, urine, and vaginal and urethral secretion were determined by bioassay. All four quinolones penetrated into vaginal and urethral secretion in concentrations several times higher than the MIC against common urinary pathogens, ciprofloxacin and norfloxacin reaching concentrations exceeding the simultaneous plasma concentrations. Because of their favorable antibacterial spectra, new quinolones should be investigated clinically for the treatment of recurrent urinary tract infection and bacterial vaginitis.
The effects of subinhibitory concentrations (1/4, 1/8, 1/16 of the MIC) of quinolones (ciprofloxacin, enoxacin, nalidixic acid, norfloxacin, ofloxacin, pefloxacin), aminoglycosides (amikacin, gentamicin, netilmicin, streptomycin, tobramycin), beta-lactams (aztreonam, ceftazidime, imipenem, ticarcilin) and macrolides (erythromycin, roxitromycin) on the excretion of alginate by a P. aeruginosa strain were studied. Both beta-lactam and macrolide antibiotics were found ineffective at the concentrations tested, except erythromycin and imipenem at 1/4 MIC. Aminoglycosides at a concentration of 1/4 MIC reduced most effectively the excretion of alginate. Quinolones were also effective at this sub-MIC; 1/16 MIC was ineffective with all antibiotics or stimulated the production of alginate.
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The prevalence and risk factors of bacteriuria on admission were determined by a multicenter prospective case-control study.
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48 patients treated with bone marrow transplantation (BMT) received the quinolone norfloxacin (NOR) in a total decontamination (TD-NOR, n = 36) or selective decontamination (SD-NOR, n = 12) regimen and were compared with a historical control group of 48 BMT patients receiving oral non-absorbable antibiotics (TD-NAA, n = 31 and SD-NAA, n = 17). 17/36 patients (47%) of group TD-NOR and 16/31 patients (52%) of group TD-NAA remained free of febrile episodes and infections. 4/12 patients (33%) of group SD-NOR and only 1/17 patients (6%) of group SD-NAA remained free of fever and infections. The use of norfloxacin in selective decontamination resulted in a statistically significant lower incidence of fever days than in patients receiving SD-NAA (p less than 0.001). These data suggest that norfloxacin may replace non-absorbable antibiotics in total and in selective decontamination regimens used for infection prophylaxis in BMT recipients.
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There are very limited data on the postmarketing outcome comparison of different guideline antibiotic regimens for patients with urinary tract infections (UTIs). We carried out a population-based comparative effectiveness study from year 2000 through 2009, using the administrative data of 2 million patients from the National Health Informatics Project of Taiwan. Treatment failure was defined as either hospitalization or emergency department visits for UTI. Odd ratios were computed using conditional logistic regression models matched on propensity score. We identified 73,675 individuals with UTI, of whom 54,796 (74.4%) received trimethoprim-sulfamethoxazole (TMP-SMX), 4184 (5.7%) received ciprofloxacin, 3142 (4.3%) received levofloxacin, 5984 (8.1%) received ofloxacin, and 5569 (7.6%) received norfloxacin. Compared with TMP-SMX, the composite treatment failure was significantly lowered for norfloxacin in propensity score (PS) matching analyses (OR, 0.73; 95% CI, 0.54-0.99). Both norfloxacin (PS-matched OR, 0.68; 95% CI, 0.47-0.98) and ofloxacin (PS-matched OR, 0.70; 95% CI, 0.49-0.99) had significantly lowered composite treatment failure rate when compared with ciprofloxacin. Subgroup analysis suggested that both norfloxacin and ofloxacin were more effective in female patients without complications (W/O indwelling catheters, W/O bedridden status and W/O spinal cord injury), when compared with either TMP-SMX or ciprofloxacin. Among outpatients receiving oral fluoroquinolone therapy for UTIs, there was evidence of superiority of norfloxacin or ofloxacin over ciprofloxacin or TMP-SMX in terms of treatment failure. Given the observational nature of this study and regional difference in antibiotic resistance patterns, more studies are required to validate our results.
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A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration.
We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins. Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay. Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined. Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity. Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake. Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml). Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings. Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease. An additional group of phototoxic drugs, quinolone antibacterials, were studied. Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake. This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins.