Efficacy of Azithromycin in the Treatment of Community-acquired Pneumonia, Including Patients with Macrolide-Resistant Streptococcus pneumoniae Infection

Background and Objective The growing problem of drug resistance among respiratory pathogens in community-acquired pneumonia (CAP), particularly Streptococcus pneumoniae, (S. pneumoniae) has complicated initial empiric therapy of CAP. This study was undertaken to evaluate the efficacy and tolerability of a 3-day course of azithromycin in adults with mild to moderately severe CAP, and to determine whether in vitro macrolide resistance among strains of S. pneumoniae is related to clinical efficacy/failure. Methods An open-label, non-comparative study was undertaken at 3 university-affiliated hospitals in Japan. Patients were eligible if they were 18 years or older and had mild or moderately severe CAP. All patients received azithromycin 500 mg/day for three days, and clinical and microbiological responses were evaluated 1 and 2 weeks after initiating therapy. Results A total of 78 patients received the study medication, 59 of whom had sufficient data available for efficacy analysis. Overall, a good clinical response with azithromycin was achieved in 49 patients (83.1%) and a microbiological response was achieved in 78.3%. Azithromycin resistance, based on CLSI criteria, was demonstrated in 85.7% (12/14) of S. pneumoniae isolates, and the presence of ermB genes was found in 50.0% (7/14). However, among patients in whom S. pneumoniae was isolated (n=17), a good clinical response was achieved in 76.5% (13/17), and the microbiological response rate was 64.3% (9/14). Furthermore, 6 of 7 patients in whom high-level resistance was documented (MICs > 256 mu g/mL and carrying ermB genes) exhibited good clinical responses. Azithromycin was well tolerated; adverse events, mainly of a gastrointestinal nature, were recorded in 6 patients (7.7%). Conclusion Most patients responed well to azithromycin, indicating that azithromycin might be clinically effective for the treatment of CAP with macrolide-resistant S. pneumoniae. However, a larger study is necessary to prove the efficacy against macrolide-resistant S. pneumoniae.