Macrolide resistance among invasive Streptococcus pneumoniae isolates

Context Macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are the mainstays of empirical pneumonia therapy. Macrolide r esistance among Streptococcus pneumoniae, the most common cause of communit y-acquired pneumonia, is increasing in the United States. Whether resistanc e is a significant problem or whether macrolides remain useful for treatmen t of most resistant strains is unknown. Objective To examine the epidemiology of macrolide-resistant pneumococci in the United States. Design and Setting Analysis of 15481 invasive isolates from 1995 to 1999 co llected by the Centers for Disease Control and Prevention's Active Bacteria l Core surveillance system in 8 states. Main Outcome Measures Trends in macrolide use (1993-1999) and resistance an d factors associated with resistance, including examination of 2 subtypes, the M phenotype, associated with moderate minimum inhibitory concentrations (MICs), and the MLS8 phenotype, associated with high MICs and clindamycin resistance. Results From 1993 to 1999, macrolide use increased 13% macrolide use increa sed 320% among children younger than 5 years. Macrolide resistance increase d from 10.6% in 1995 to 20.4% in 1999. M phenotype isolates increased from 7.4% to 16.5% (P<.001), while the proportion with the MLSB phenotype was st able (3%-4%). The median erythromycin MIC (MIC50) of M phenotype isolates i ncreased from 4 <mu>g/mL to 8 mug/mL. In 1999, M phenotype strains were mor e often from children than persons 5 years or older (25.2% vs 12.6%; P<.001 ) and from whites than blacks (19.3% vs 11.2%; P<.001). Conclusions In the setting of increasing macrolide use, pneumococcal resist ance has become common. Most resistant strains have MICs in the range in wh ich treatment failures have been reported. Further study and surveillance a re critical to understanding the clinical implications of our findings.