Clinical relevance of macrolide-resistant Streptococcus pneumoniae for community-acquired pneumonia

Macrolides are often the first choice for empirical treatment of community-acquired pneumonia. However, macrolide resistance among Streptococcus pneumoniae has escalated at alarming rates in North America and worldwide. Macrolide resistance among pneumococci is primarily due to genetic mutations affecting the ribosomal target site (ermAM) or active drug efflux (mefE). Prior antibiotic exposure is the major risk factor for amplification and perpetuation of resistance. Clonal spread facilitates dissemination of drug-resistant strains. Data assessing the impact of macrolide resistance on clinical outcomes are spare. Many experts believe that the clinical impact is limited. Ribosomal mutations confer high-grade resistance, whereas efflux mutations can likely be overridden in vivo. Favorable pharmacokinetics and pharmacodynamics, high concentrations at sites of infections, and additional properties of macrolides may enhance their efficacy. In this article, we discuss the prevalence of macrolide resistance among S. pneumoniae, risk factors and mechanisms responsible for resistance, therapeutic strategies, and implications for the future.