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.

Abstract 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 available for the management of infections caused by this pathogen. Although the fluoroquinolones appear to retain activity against macrolide-resistant pneumococci, limited clinical data exist to support their use in this setting. Objective: This study integrated data from 4 clinical trials to determine whether the fluoroquinolone levofloxacin is an effective therapeutic agent for community-acquired pneumonia (CAP) caused by macrolide-resistant S pneumoniae . Methods: Across the 4 trials, 271 adult patients with CAP were diagnosed with 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, ≤0.25 μg/mL; intermediate, 0.5 μ;g/mL; resistant, ≥1.0 μ;g/mL). All patients received levofloxacin (500 mg once daily for 7–14 days) and were analyzed at a posttherapy visit (2–5 days after completion of therapy) for clinical and microbiologic outcomes; in 3 trials, patients were also examined at a poststudy visit (14–28 days after completion of treatment). Clinical and microbiologic outcomes were analyzed 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 with isolates resistant to erythromycin, of whom 26 (96.3%) were clinical successes. 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 clinical relevance of macrolide resistance, levofloxacin may be a useful therapeutic option in patients with CAP caused by macrolide-resistant S pneumoniae . However, caution may be warranted to prevent overprescription of levofloxacin and other fluoroquinolones, given the potential for the development of resistance in S pneumoniae .