Pharmacodynamic evaluation of ofloxacin and trimethoprim-sulfamethoxazole in vaginal fluid of women treated for acute cystitis

Abstract

Vaginal colonization with Escherichia coli is an integral step in the development of acute cystltis, and persistent vaginal coliform colonization may also be a predisposing step to recurrent urinary tract infections. For this reason, we evaluated antibiotic concentrations in the vaginal fluid, serum, and urine and the vaginal colonization by E. coil of 56 women receiving either ofloxacin (200 mg orafly twice a day) or trimethoprimsudfamethoxazole (TMP-SMX) (160/800 mg oraHly twice a day) for the treatment of acute cystitis. Ofloxacin and trimethoprim both penetrated into vaginal fluid to a considerably greater extent than sulfamethoxazole. Among 33 patients given ofloxacin, the concentration of the drug in vaginal fluid during one dosage interval ranged from 1.6 to 21.6 >g/ml. In 21 women given TMP-SMX the range of drug concentrations in vaginal fluid was 2.6 to 32.5 ,g/ml for TMP and 1.0 to 6.2 ,ug/ml for SMX. Treatment with both ofloxacin and TMP-SMX remarkably reduced vaginal colonization by E. coil during and up to 30 days after therapy. For the ofloxacin-treated women, eradication of vaginal E. col was aated with a hig ratio of drug concentration in vaginal fluid to that in serum. We conclude that ofloxacin and TMP both achieve hig concentrations in vaginal fluid and are equaHly successful in eradicating E. coil from the vagina.Vaginal colonization with Escherichia coli is an integral first step in the pathogenesis of acute cystitis, and persistent vaginal colonization with E. coli has been associated with the development of recurrent urinary infections in women (2,7,13 Vaginal fluid was obtained by using a sterile preweighed 25-mm-diameter filter paper disk (no. 42; Whatman, Inc., Clifton, N.J.) that was stored in a sealed test tube. During the speculum examination, the disk was placed high on the vaginal wall for 15 s, with care taken to avoid introital contamination. The disk was removed with sterile forceps and placed into the original test tube, and the tube was sealed tightly and stored at -70°C until analysis. A vaginal culture was also obtained by using a sterile cotton-tipped swab.Andbiotic therapy. As previously described (3), patients were randomly assigned to receive either oral ofloxacin (200 * Corresponding author. mg) or TMP-SMX (160/800 mg) twice a day for 3 to 7 days. Patients were given the first dose in the clinic and were instructed to take their assigned doses approximately every 12 h. Diaries were used by the patients to record the time of each dose.Foflow-up visits. Patients returned to the clinic during therapy at day 2 or 3 and at days 5 to 9 and 30 posttherapy. During these visits, vaginal and urine cultures were again obtained. Blood and vaginal fluid samples for determination of antibiotic concentrations were collected at the first follow-up visit. All specimens were collected within 15 min of each other for each patient.Bacteriology. All cultures and susceptibility tests were performed in our laboratory as previously described (8 (82:18, vol/vol). No interferences from either e...

Ceftibuten versus trimethoprim-sulfamethoxazole for oral treatment of febrile urinary tract infection in children

“…Follow-up was scheduled 4-10 days post-treatment (days [14][15][16][17][18][19][20]. The investigator judged the clinical response to treatment, and a urine sample for urinalysis and culture was collected as bag urine or as voided midstream urine.…”

“…The perprotocol (PP) population was derived from the ITT population but included only those patients with bacteria susceptible to the drug they had been allocated to and those who had strictly followed the protocol by taking the trial drug for 10 days, returning for a follow-up visit 4-10 days after the end of treatment (days [14][15][16][17][18][19][20] and delivering a urine sample for culture.…”

Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis

“…There are no previously published data on the effects of ofloxacin on perineal flora with which to compare our results, but in comparison with other agents used to treat UTI, ofloxacin is among the most effective of agents in terms of eradicating vaginal E. coli. This may result from high concentrations of drug found in vaginal fluid (29). Although studies of larger numbers of patients are necessary to determine whether this property has a beneficial effect in reducing the risk of recurrent UTI in women treated with ofloxacin, it can be inferred from experience with other antimicrobial agents that this is likely (10).…”

Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers

“…or p.o., to volunteers or patients with normal renal function (1,5). Previous studies have not shown any change in the bioavailability of ofloxacin in infectious disease patients versus normal volunteers (1,2,6,7,11,13,14). The bioavailability of ofloxacin has been previously investigated after administration of single doses (5,15), but to our knowledge this is the first study that has investigated it under steady-state conditions.…”