Effectiveness of levofloxacin for adult community-acquired pneumonia caused by macrolide-resistant Streptococcus pneumoniae: Integrated results from four open-label, multicenter, phase III clinical trials

Background: The rate of macrolide resistance among Streptococcus pneumoniae clinical isolates is rising. Coresistance to several unrelated classes of antimicrobial agents is common and may limit the treatment options availabl e for the management of infections caused by this pathogen. Although the fl uoroquinolones appear to retain activity against macrolide-resistant pneumo cocci, limited clinical data exist to support their use in this setting. Objective: This study integrated data from 4 clinical trials to determine w hether the fluoroquinolone levofloxacin is an effective therapeutic agent f or community-acquired pneumonia (CAP) caused by macrolide-resistant S pneum oniae, Methods: Across the 4 trials, 271 adult patients with CAP were diagnosed wi th infections caused by S pneumoniae; these constituted the intent-to-treat population. Clinical isolates obtained from each patient at admission were tested using broth microdilution for in vitro sensitivity to the macrolide erythromycin (minimum inhibitory concentration breakpoints: susceptible, l ess than or equal to0.25 mug/mL; intermediate, 0.5 mug/mL: resistant, great er than or equal to1.0 mug/mL). All patients received levofloxacin (500 mg once daily for 7-14 days) and were analyzed at a posttherapy visit (2-5 day s after completion of therapy) for clinical and microbiologic outcomes; in 3 trials, patients were also examined at a poststudy visit (14-28 days afte r completion of treatment). Clinical and microbiologic outcomes were analyz ed in patients infected with macrolide-resistant and macrolide-susceptible S pneumoniae. Results: A total of 235 evaluable patients infected with S pneumoniae were identified from the 4 trials. Twenty-seven (11.5%) patients were infected w ith isolates resistant to erythromycin, of whom 26 (96.3%) were clinical su ccesses. By comparison, the clinical success rate in patients infected with erythromycin-susceptible isolates was 97.7%. Conclusions: These results suggest that if future studies demonstrate the c linical relevance of macrolide resistance, levofloxacin may be a useful the rapeutic option in patients with CAP caused by macrolide-resistant S pneumo niae. However, caution may be warranted to prevent overprescription of levo floxacin and other fluoroquinolones. given the potential for the developmen t of resistance in S pneumoniae.