Serotype Emergence and Genotype Distribution among Macrolide-Resistant Invasive Streptococcus Pneumoniae Isolates in the Postconjugate Vaccine (PCV-7) Era

Abstract

We conducted population-based surveillance for pneumococcal bacteremia within a 5-county region surrounding Philadelphia from October 2001 through September 2008, the period following introduction of the seven-valent pneumococcal conjugate vaccine. Erythromycin resistance increased from 14.7% in 2001-2002 to 20.3% in 2007-2008, while the resistance rate to penicillin (MIC, ≥2 μg/ml) decreased from 7.2% to 4.2% during the same period. The most predominant serotypes associated with erythromycin resistance in 2007-2008 included 19A (29.7%), 15A (29.2%), 6C (10.1%), 3 (5.6%), and 6A (4.5%). The molecular mechanisms for the increasing erythromycin resistance were mainly due to the growing presence of mef(A) negative erm (B) ⁺ and mef(A) ⁺ erm (B) ⁺ genotypes, which increased from 20.0% to 46.1% and from 1.8% to 19.1%, respectively, from 2001-2002 to 2007-2008. However, mef(A) -mediated erythromycin resistance decreased from 72.7% in 2001-2002 to 34.8% in 2007-2008. Serotypes related to the erm (B) gene were 15A (45.6%), 19A (20.9%), 3 (10.1%), and 6B (6.3%); serotypes related to the mef(A) gene were 6A (18.6%), 19A (15.0%), 6C (9.3%), and 14(8.4%); serotypes associated with the presence of both erm (B) and mef(A) were 19A (81.5%), 15A (7.7%), and 19F (6.2%). Pulsed-field gel electrophoresis analysis demonstrated that erythromycin-resistant isolates within the 19A serotype were genetically diverse and related to several circulating international clones. In contrast, erythromycin-resistant isolates within the 15A serotype consisted of clonally identical or closely related isolates.