Efficacy and safety of ten day moxifloxacin 400 mg once daily in the treatment of patients with community-acquired pneumonia

Community-acquired pneumonia (CAP) remains a common and serious illness wit h approximately 2-4 million cases reported annually. Management of CAP is t herapeutically challenging due to the increasing prevalence of penicillin- and macrolide-resistant pneumococci and beta-lactamase producing Haemohphil us influenzae, as well as the increased recognition of 'atypical' pathogens , such as Chlamydia pneumoniae and Mycoplasma pneumoniae, and the frequent need for empiric therapy. We aimed to evaluate the safety and efficacy of moxifloxacin in the treatme nt of patients with CAP. To do this we carried out a prospective, uncontrol led, non-blind, Phase III clinical trial, in 27 U.S. centers. Patients incl uded in the study were over 18 years of age with signs and symptoms of CAP confirmed by evidence of a new or progressive infiltrate on chest radiograp h. The intervention used was moxifloxacin 400 mg PO once daily for 10 days. Sputum samples were collected pretherapy for Gram stain and culture for typ ical organisms. Culture and serological testing for Chlamydia pneumoniae an d Mycoplasma pneumoniae was also performed. Susceptibility to moxifloxacin was determined by disk diffusion and MIG. Clinical and bacteriological resp onses were determined at the end of therapy (0-6 days post-therapy), follow -up (14-35 days post-therapy) and overall (end of therapy plus follow-up). Analyses were performed on both valid for efficacy and intent-to-treat popu lations. The primary efficacy variable was overall clinical resolution. Of 254 patients enrolled in the Study, 196 patients were included in the ef ficacy analyses. The majority of patients were male (58%) and Caucasian (85 %) with a mean age of 49 years (range: 18 to 85 years). Only 3% of patients were hospitalized pretherapy. The most common pretherapy organisms identif ied, by culture or serology, in the valid for efficacy population (i.e. 147 organisms among 116 patients), were: Chlamydia pneumoniae (n=63; 54%), Myc oplasma pneumoniae (n=29; 25%), Streptococcus pneumoniae (n=14; 12%) and Ha emophilus influenzae (n=13; 10%). End of therapy, follow-up and overall cli nical resolution rates for the valid for efficacy population were 94%, 93% and 93%, respectively. The 95% CT for the overall clinical resolution rate was 88.1%, 95.9%. The overall bacteriological response for patients diagnos ed by culture or serological criteria, was 91% (95% Cl=84%, 96%). For patie nts who only met serological criteria for infection, the overall bacteriolo gical response was 94% (60/64). Bacterial response rates for the four most commonly isolated pathogens were: 89% (56/63) for C. pneumoniae, 93% (27/29 ) for M. pneumoniae, 93% (13/14) for S. pneumoniae and 85% (11/13) for H, i nfluenzae. Drug-related adverse events were reported in 33% (85/254) of mox ifloxacin-treated patients. Nausea (9%), diarrhea (6%) and dizziness (4%) w ere the most commonly reported adverse events. Atypical organisms were isolated in high frequency among patients with CAP. Moxifloxacin 400 mg once daily for 10 days was effective and well-tolerate d in the treatment of these adult patients with CAP. Moxifloxacin offers an effective treatment alternative for CAP due to both typical and atypical b acterial pathogens.