A prospective, double-blind, multicenter study comparing clarithromycin extended-release with trovafloxacin in patients with community-acquired pneumonia

Background: Treatment guidelines for community-acquired pneumonia (CAP) generally include use of a macrolide, a fluoroquinolone, or doxycycline, although there is some debate concerning the use of a fluoroquinolone. Objective: The efficacy and tolerability of a new once-daily, extended-release (ER) formulation of clarithromycin were compared with those of a fluoroquinolone, trovafloxacin, in the treatment of patients with CAP. Methods: This was a prospective, multicenter, double-blind, double-dummy, parallel-roup trial in which outpatients were randomized to receive 7 days of once-daily treatment with either clarithromycin ER (two 500-mg tablets) or trovafloxacin (200 mg). Eligible patients were greater than or equal to18 years old with signs and symptoms of pneumonia, radiologic evidence of an acute infiltrate, and mild to moderate infection, as classified by the investigator. Results: One hundred seventy-six patients were randomized to study treatment. They were primarily white (88%) and equally distributed between the sexes (52% female). Their mean (+/-SD) age was 47.5 +/- 16.2 years. Results were similar between treatment groups in rates of clinical cure, microbiologic cure, bacteriologic eradication, and radio logic success at the test-of-cure visit (14-21 days posttreatment) for both the perprotocol and intent-to-treat analyses. Among clinically evaluable patients, clinical cure rates for clarithromycin ER and trovafloxacin were 87% (74/85) and 95% (63/66), respectively, and radiologic success rates were 95% (80/84) and 95% (63/66), respectively. There were no statistically significant differences between groups. In clinically and microbiologically evaluable patients, overall bacteriologic eradication rates were 89% (85/95) for clarithromycin ER and 96% (64/67) for trovafloxacin, with no significant differences between groups. Both antibiotics demonstrated high eradication rates against target microorganisms. There were no clinically meaningful differences in the incidence of specific drug-related adverse events. The majority of drug-related adverse events (>90%) were considered mild or moderate and resolved without the need for additional treatment. Conclusions: Although the study was prematurely terminated, resulting in inadequate power to demonstrate equivalence, once-daily clarithromycin ER was effective and well tolerated in the treatment of ambulatory adult (age greater than or equal to18 years) outpatients with CAP.