Implications of antimicrobial resistance in the empirical treatment of community-acquired respiratory tract infections: the case of macrolides

Macrolide resistance among pneumococci is increasing worldwide and is associated with increasing macrolide use. Recent studies show that use of macrolides and azalides increases nasopharyngeal carriage of both macrolide-resistant and penicillin-resistant pneumococci. Carriage of a resistant pneumococcus may foster dissemination. The clinical relevance of in vitro resistance has been debated. However, recent data from a matched case-control study showed that 18 (24%) of 76 patients had breakthrough bacteraemia with an erythromycin-resistant pneumococcus while taking a macrolide, whereas none of the 136 matched controls with an erythromycin-susceptible pneumococcal bacteraemia was taking a macrolide (P = 0.0000001). Moreover, five (24%) of 21 patients bacteraemic with the low-level resistant M phenotype and none of the 40 matched controls were taking a macrolide (P = 0.00157). These data indicate that macrolide resistance due to both the efflux and the methylase mechanisms is clinically relevant. Furthermore, they favour guidelines for the empirical treatment of outpatients with community-acquired pneumonia that recommend high-dose oral amoxicillin and reserve coverage of atypical pathogens for selected high-risk populations.