Comparison of a 3-day with a 1-day regimen of an extended-release formulation of ciprofloxacin as antimicrobial prophylaxis for patients undergoing transrectal needle biopsy of the prostate.

OBJECTIVE: To compare the clinical and bacteriological efficacy and the clinical safety of a 1-day with a 3-day regimen of an extended-release formulation of ciprofloxacin (ciprofloxacin XR) given as antimicrobial prophylaxis to men undergoing transrectal needle biopsy of the prostate (TRNBP). PATIENTS AND METHODS: This was a multicentre, prospective, international, double-blind study in patients who required TRNBP. Patients were randomized to receive oral ciprofloxacin XR 1000 mg as either a 1-day or a 3-day regimen. Single doses were given at 24 h before, 2-3 h before, and 24 h after TRNBP. Patients in the 1-day regimen had placebo instead of the first and third doses of ciprofloxacin. RESULTS: Of 497 patients enrolled, 247 were randomized to 1-day ciprofloxacin XR and 250 to the 3-day regimen. In the population valid for microbiological efficacy, the final assessment identified bacteriological success (primary efficacy endpoint) in more patients who had the 3-day regimen (98%) than in those who received the 1-day regimen (94.8%, 95% confidence interval, CI, - 6.1%, 0.8%), although the difference was not statistically significant. In this population, the clinical response at the final visit was 98.5% and 96.7% for patients receiving the 3-day and the 1-day regimens, respectively (95% CI - 5.2%, 0.8%). However, in the clinical efficacy population the clinical success rate was significantly greater for the 3-day (99.0%) than for the 1-day regimen (95.8%; 95% CI - 6.4%, - 0.3%). In a multivariate analysis, patients with diabetes mellitus and patients with a history of prostatitis had higher microbiological and clinical failure rates, respectively, than those without such conditions. For these patients, all failures occurred among those treated with the 1-day regimen. CONCLUSION: As defined by bacteriological success in the population assessed for microbiological efficacy, prophylaxis with one dose of ciprofloxacin XR was statistically no worse than a 3-day regimen. However, in all efficacy analyses, bacteriological and clinical success rates were consistently lower for the 1-day than for the 3-day treatment. Thus, for selected patients undergoing TRNBP, there might be a role for 3-day preventive therapy with ciprofloxacin XR.

Retrospective analysis of the safety profile of oral moxifloxacin in elderly patients enrolled in clinical trials.

BACKGROUND AND OBJECTIVE: As aging is associated with physiological changes, including renal and hepatic insufficiency, and a higher risk of drug interactions, special attention needs to be directed towards the safety of medications in the elderly. The objective of this analysis was to evaluate the safety of oral moxifloxacin in elderly patients who were enrolled in clinical trials and to compare these results to those of other commonly used antibacterials. METHODS: Safety data from 27 prospective, randomised, comparative phase II/III trials of oral moxifloxacin included in the Bayer clinical trial database were pooled and analysed by age group (<65 years of age, 65-74 years of age, > or = 75 years of age) and by treatment group (moxifloxacin vs comparator). The primary endpoints included rates of treatment-emergent adverse events (all adverse events regardless of causality), drug-related adverse events, drug-related serious adverse events, deaths and premature discontinuations because of a treatment-emergent adverse event. A treatment by age group interaction test was used to determine if the comparison between moxifloxacin and the comparator group in the incidence rates of any treatment-emergent or drug-related adverse events were affected by increasing age. RESULTS: Of the 12 231 patients who had valid safety data, 6270 had been treated with oral moxifloxacin and 5961 with a comparator antibacterial. The most frequently used comparators were cefuroxime and clarithromycin. Most patients (n = 9671) were <65 years of age (4939 moxifloxacin, 4732 comparator); 1636 patients were 65-74 years of age (842 moxifloxacin, 794 comparator); and 924 patients were > or = 75 years of age (489 moxifloxacin, 435 comparator). The treatment by age group interaction test revealed that the comparison of drug-related adverse event rates between the moxifloxacin and comparator group were not affected by increasing age (p = 0.43). Rates of premature termination between the moxifloxacin and comparator treatment groups also did not increase with age (p = 0.552). No arrhythmias related to corrected QT (QTc) interval prolongation were reported following oral moxifloxacin or comparator treatment in this large group of young and elderly patients. Overall, the number of deaths was similar between the treatment groups (17 moxifloxacin, 19 comparator). CONCLUSIONS: Drug-related adverse event rates associated with oral moxifloxacin or the comparator therapy used in these studies did not significantly increase with advancing age. This pooled analysis suggests that oral moxifloxacin can be safely used in elderly patients with characteristics consistent with those enrolled into the clinical trials.

Clinical experience with moxifloxacin in patients with respiratory tract infections.

BACKGROUND: Moxifloxacin is an advanced-generation fluoroquinolone used primarily for the treatment of respiratory tract infections. OBJECTIVE: To further investigate moxifloxacin's general and cardiac safety and evaluate its efficacy in the community practice setting in a large surveillance study. METHODS: A total of 18,409 outpatients with suspected bacterial episodes of acute sinusitis, acute exacerbation of chronic bronchitis, or community-acquired pneumonia of mild to moderate severity were enrolled at 3377 community practice sites. Patients with sinusitis or pneumonia received once-daily oral moxifloxacin 400 mg for 10 days; those with bronchitis received 5 days' treatment. At follow-up, within 48 hours after the end of treatment, adverse event information was collected. An external safety committee assessed possible cardiac-related events. Efficacy was also evaluated at follow-up via the degree of resolution of clinical signs and symptoms. RESULTS: Of 18,374 safety-valid patients, 17.7% experienced adverse events and 14.3% experienced drug-related adverse events. The most common drug-related adverse events were nausea (5.3%), diarrhea (2.2%), and dizziness (2.0%). There was no clinical evidence of increased risk of cardiac arrhythmias with moxifloxacin treatment. Of 17,137 patients included in the efficacy analysis, 92.9% overall experienced clinical cure or improvement (92.8% with sinusitis, 92.9% with bronchitis, 94.1% with pneumonia). CONCLUSIONS: Once-daily oral moxifloxacin 400 mg was shown to be safe and effective in this trial for the treatment of respiratory tract infections of suspected bacterial origin in the clinical practice setting.

Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial.

BACKGROUND: Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE: To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN: Randomized, double-blind multicenter trial. SETTING: Seven U.S. university-affiliated hospitals and one private research center. PATIENTS: Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS: Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS: Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS: 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION: Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.

Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the first choice for empiric therapy of acute uncomplicated urinary tract infection (UTI) in women. In areas where resistance to TMP/SMX is known to be high, ciprofloxacin and other fluoroquinolones are recommended as first-line choices for the empiric therapy of UTI. OBJECTIVE: This study compared the efficacy and safety profile of once-daily extended-release ciprofloxacin 500 mg (referred to hereafter as ciprofloxacin QD) with those of conventional ciprofloxacin 250 mg BID, each administered orally for 3 days, in the treatment of uncomplicated UTI in women. METHODS: In this multicenter, prospective, randomized, double-blind, double-dummy, Phase III trial, adult women with clinical signs and symptoms of acute uncomplicated UTI, pyuria, and a positive pretherapy urine culture (>/=10(5) colony-forming units/mL) received ciprofloxacin QD or ciprofloxacin BID. Bacteriologic and clinical outcomes were assessed at the test-of-cure visit (4-11 days after completion of therapy) and the late follow-up visit (25-50 days after completion of therapy). RESULTS: The intent-to-treat population consisted of 891 patients (444 ciprofloxacin QD, 447 ciprofloxacin BID); 422 patients were evaluable for efficacy (199 ciprofloxacin QD, 223 ciprofloxacin BID). At the test-of-cure visit, bacteriologic eradication was achieved in 94.5% (188/199) of the ciprofloxacin QD group and 93.7% (209/223) of the ciprofloxacin BID group (95% CI, -3.5 to 5.1). Clinical cure was achieved in 95.5% (189/198) of the ciprofloxacin QD group and 92.7% (204/220) of the ciprofloxacin BID group (95% CI, -1.6 to 7.1). Bacteriologic and clinical outcomes at the late follow-up visit were consistent with the test-of-cure findings. The rate of eradication of Escherichia coli, the most prevalent organism, was >97% in each treatment group. Rates of drug-related adverse events were similar with the once- and twice-daily ciprofloxacin regimens (10% and 9%, respectively). CONCLUSION: Extended-release ciprofloxacin 500 mg given once daily for 3 days was as effective and well tolerated as conventional ciprofloxacin 250 mg given twice daily for 3 days in the treatment of acute uncomplicated UTI in women.