Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections.
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OBJECTIVES: Antimicrobial drug use is believed to be an important risk factor for the emerging problem of antimicrobial drug resistance, yet strong evidence for the causal relationship in community settings has been limited. Detailed analysis of this risk factor at the level of the individual patient has been hampered by limited availability of drug exposure data among patients with outpatient infections. We used a novel data system to identify patterns of individual antimicrobial drug exposures associated with trimethoprim-sulfamethoxazole-resistant urinary tract infections (UTIs). MATERIALS AND METHODS: This was a retrospective case-control study. Subjects were veterans with Gram-negative UTIs seen at the Philadelphia VA Medical Center from 1 July 1996 to 31 December 1999. Subjects were linked to a national VA outpatient pharmacy database. Cases and controls were identified based on the results of trimethoprim-sulfamethoxazole susceptibility testing. RESULTS: Three hundred and ninety-three veterans with UTIs could be linked to electronic pharmacy records. The overall rate of trimethoprim-sulfamethoxazole drug resistance was 13%, without significant annual variation. Antimicrobial drug exposure within 6 months was strongly associated with the probability of a trimethoprim-sulfamethoxazole-resistant infection (OR = 4.1, 95% CI 2.2-7.5). This association extended to exposure to other antimicrobial drugs in addition to trimethoprim-sulfamethoxazole and the overall association displayed a dose-response relationship in terms of the number of prior drug exposures. CONCLUSIONS: Prior antimicrobial drug exposure is a strong risk factor for infection with trimethoprim-sulfamethoxazole-resistant Gram-negative bacteria among patients with UTIs. (+info)
Effectiveness of estriol-containing vaginal pessaries and nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in postmenopausal women.
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We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal (NM) therapy for preventing urinary tract infection (UTI) in postmenopausal women with recurrent UTI. Over a period of 9 months, 86 women received an estriol-containing vaginal pessary (0.5 mg estriol) twice weekly, and 85 women received NM (100 mg) once daily. We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM (P=.0003). Twenty-eight women (32.6%) who received estriol had no episodes of UTI versus 41 women (48.2%) in the NM group. There was a significant increase in the number of superficial cells in women who received estriol, whereas in the NM group, no such changes occurred. However, there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol. Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women. (+info)
In vitro activity of C-8-methoxy fluoroquinolones against mycobacteria when combined with anti-tuberculosis agents.
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OBJECTIVES: To examine the effect of first-line and second-line anti-tuberculosis agents on the ability of fluoroquinolones to kill mycobacteria. METHODS: A clinical isolate of Mycobacterium tuberculosis and a laboratory strain of Mycobacterium smegmatis were grown in liquid medium and treated with a fluoroquinolone in the presence or absence of anti-tuberculosis agents. Bacterial survival was determined by viable colony counts on agar medium. RESULTS: When moxifloxacin activity was examined in two-drug combinations containing traditional anti-tuberculosis agents, activity was greater than either compound alone with isoniazid, capreomycin and low, but not high, concentrations of rifampicin. Cycloserine contributed no additional activity, and ethambutol interfered with the lethal action of moxifloxacin and gatifloxacin. Experiments with M. smegmatis confirmed that both rifampicin and ethambutol reduce fluoroquinolone lethality. Moreover, ethambutol increased the recovery of fluoroquinolone-resistant mutants newly created by ethyl methanesulphonate treatment. CONCLUSIONS: The intrinsic bactericidal activity of C-8-methoxy fluoroquinolones can be adversely affected by some agents currently used for treatment of tuberculosis. (+info)
In vitro evaluation of a new treatment for urinary tract infections caused by nitrate-reducing bacteria.
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Dietary and endogenous nitrates are excreted in urine, and during infection with nitrate-reducing bacteria they are reduced to nitrite. At a low pH nitrite is converted to a variety of nitrogen oxides that are toxic to bacteria. We hypothesized that acidification of nitrite-rich infected urine would result in the killing of the nitrate-reducing bacteria. An Escherichia coli control strain and a mutant lacking nitrate reductase activity were preincubated in urine supplemented with sodium nitrate (0 to 10 mM) at pH 7.0. Then, the nitrite-containing bacterial culture was transferred (and diluted 1/10) to slightly acidic urine (pH 5 and 5.5) containing ascorbic acid (10 mM) and growth was monitored. The control strain produced nitrite in amounts related to the amount of nitrate added. This strain was killed when the culture was transferred to acidic urine. In contrast, the mutant that did not produce nitrite retained full viability. When control bacteria were grown in acidic urine with nitrate and ascorbic acid present from the start of the experiment, no inhibition of growth was noted. The MICs and minimal bactericidal concentrations of sodium nitrite-ascorbic acid in acidic urine were comparable to those of conventional antibiotics. Preincubation of nitrate-reducing E. coli in nitrate-rich urine leads to the accumulation of nitrite. Subsequent acidification of the urine results in generation of nitrogen oxides that are bactericidal. Killing, however, requires a sequential procedure in which the bacteria are first allowed to grow in a nitrate-rich neutral environment, later followed by acidification. We speculate that ingestion of nitrate followed some hours later by acidification of urine could be a new therapeutic strategy for the treatment of urinary tract infections. (+info)
Use of administrative healthcare claims to examine the effectiveness of trimethoprim-sulfamethoxazole versus fluoroquinolones in the treatment of community-acquired acute pyelonephritis in women.
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OBJECTIVE: To evaluate the effectiveness of trimethoprim-sulfamethoxazole and fluoroquinolones in the treatment of community-acquired acute pyelonephritis. PATIENTS AND METHODS: We identified a population-based cohort of non-pregnant women aged 18-65 years, initially treated with trimethoprim-sulfamethoxazole or a fluoroquinolone for community-acquired pyelonephritis in an ambulatory care setting. Subjects were identified from a healthcare claims database in Manitoba, Canada for the period 15 February 1996 to 31 March 1999. Subsequent treatment failure, as evidenced by the provision of additional treatment up to 42 days post-diagnosis, was compared between the two treatments. RESULTS: A total of 1084 women met inclusion criteria: 653 (60.2%) treated with trimethoprim-sulfamethoxazole and 431 (39.8%) treated with a fluoroquinolone. Treatment outcomes were affected by subject age. At age 20, treatment with a fluoroquinolone resulted in a reduced probability of treatment failure compared with trimethoprim-sulfamethoxazole (odds ratio, 0.56; 95% CI, 0.33-0.97). At age 60, there was no difference in the probability of treatment failure (odds ratio, 1.61; 95% CI, 0.82-3.16). No other subject characteristics impacted comparative effectiveness; however, several characteristics increased the odds of treatment failure irrespective of the initial antibiotic. These included: recent urinary tract infection (odds ratio, 2.07; 95% CI, 1.14-3.57), recent antibiotic use (odds ratio, 1.40; 95% CI, 1.00-1.96;), and a treatment duration of less than 10 days (odds ratio, 2.18; 95% CI, 1.59-2.99). CONCLUSION: Younger subjects ( approximately 20 years) treated with fluoroquinolones were less likely to experience treatment failure than those treated with trimethoprim-sulfamethoxazole. Treatment durations of less than 10 days resulted in a higher probability of treatment failure regardless of the initial antibiotic. (+info)
Effect of oral administration of sulfadiazine and trimethoprim in combination on thyroid function in dogs.
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The effect of oral administration of sulfadiazine and trimethoprim in combination on serum concentrations of thyroxine (T4), triiodothyronine (T3) and free thyroxine (fT4) and the thyroid hormone response to thyrotropin administration was assessed. Six dogs were administered sulfadiazine (12.5 mg/kg) and trimethoprim (2.5 mg/kg) orally for 28 days; six untreated dogs acted as controls. Serum T4, T3 and fT4 were determined weekly during and for four weeks after treatment. Thyrotropin response tests were performed prior to treatment, after four weeks of treatment and three weeks after stopping treatment. There were no significant differences in mean serum T4, T3 or fT4 concentrations between treated and control groups at any time during the study. Mean concentration of serum T4 over time did not differ significantly from baseline concentration in either group. Significant differences in the mean serum T3 and fT4 concentrations occurred at several time points in treatment and control groups, and were apparently unrelated to treatment. Significant differences in the T4 or T3 response to thyrotropin administration within or between groups were not present. Serum T3 and fT4 concentrations fluctuate in normal dogs. Administration of sulfadiazine and trimethoprim in combination does not affect tests of thyroid function in the dog. (+info)
Prevalence of dfr genes associated with integrons and dissemination of dfrA17 among urinary isolates of Escherichia coli in Korea.
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OBJECTIVES: The association of trimethoprim-resistant dfr genes with integrons was investigated in urinary Escherichia coli isolates in Korea from the last two decades. METHODS: Of 623 E. coli isolates from urine specimens, 421 trimethoprim-resistant isolates were studied for dfr genes associated with integrons. Integrase genes were amplified and the PCR products restricted using HinfI to classify integron types. Gene cassette regions for the class 1 and class 2 integrons were amplified and sequenced. PFGE was performed to determine the epidemiological relationship of E. coli isolates. RESULTS: The carriage of class 1 integrons was found to be significantly higher in trimethoprim-resistant isolates (69%) than in trimethoprim-susceptible isolates (19%). Among the trimethoprim-resistant isolates, the frequency of dfr genes associated with class 1 integrons increased sharply from 10% of the isolates during 1980-1985 to 53% during 1996-1997 and to 46% during 2001-2002. Five different dfr cassettes--dfrA1, dfrA5, dfrA7, dfrA12 and dfrA17--were identified among the urinary E. coli isolates from the last two decades; dfrA12 was the most prevalent during 1980-1985 and dfrA17 during 1996-1997 and 2001-2002. The majority of dfr genes associated with class 1 integrons were conjugally transferable to recipient E. coli strains. The E. coli isolates that carried dfrA17 associated with class 1 integrons were found to be phylogenetically unrelated, indicating that dfrA17 was widely distributed in the different clones of E. coli. CONCLUSION: Class 1 integrons were found to be an important genetic element of resistance to trimethoprim among urinary E. coli in Korea, and the prevalence of dfrA17 was mainly due to the horizontal transfer of class 1 integrons through conjugative plasmids. (+info)
Prevalence and treatment of Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in patients with non-gonococcal urethritis.
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The aim of present study was to evaluate the occurrence of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum in non-gonococcal urethritis (NGU) and to determine the bacterial resistance to six antibiotics in order to determine the most suitable treatment strategy. A total of 50 patients were enrolled into the study. Urethral samples were taken with a dacron swab placed into urethra 2 - 3 cm in males, and vaginal samples were taken from the endocervical region in women. The patient samples that did not grow Neisseria gonorrhoeae were accepted as NGU. Direct immunofluorescence technique was used for the investigation of C. trachomatis. Mycoplasma IST was used for the isolation of M. hominis and U. urealyticum. U. urealyticum was isolated from 24 patients. Thirteen of them had only U. urealyticum, and the rest had mixed pathogen organisms (7 U. urealyticum + M. hominis; 3 U. urealyticum + C. trachomatis, and 1 U. urealyticum + M. hominis + C. trachomatis). C. trachomatis was detected in 12 patients. While 8 patients had C. trachomatis only, the rest had a mixture of the pathogen organisms listed above. Partner examinations could be performed for only 22 patients' partners. In the evaluation of antibiotic susceptibility, higher resistance was obtained against ofloxacin in U. urealyticum, and against erythromycin with M. hominis. Our results indicated that doxycycline or ofloxacin should be the first choice when empirical treatment is necessary. (+info)