Distribution of macrolide resistance genes erm(B) and mef(A) among 160 penicillin-intermediate clinical isolates of Streptococcus pneumoniae isolated in Southern France

Two prevalent mechanisms of macrolide resistance are currently described in pneumococci: production of rRNA methylase that modify 23S ribosomal RNA resulting in MLS B phenotype, and an active efflux system resulting in M-phenotype. These two mechanisms are mediated by erm(B) and mef(A) genes respectively. Several studies reported a predominance of mef(A) gene in United-States and Canada. In European countries, erm(B) determinant is prevalent and mef(A)-mediated erythromycin resistance was recently reported in about 10% of strains in Belgium and Italy. In order to evaluate implication of mef(A) gene in pneumococci erythromycin resistance, 160 clinical isolates of S. pneumoniae with low-level of penicillin resistance and resistance to macrolides recovered between April 1999 and April 2000 were collected. These isolates were tested for their macrolide susceptibility by disc diffusion method, 155 showed the MLS B phenotype and 5 the M phenotype. Genotypic analysis was performed by erm(B) and mef(A) specific-mediated PCR: erm(B) gene was detected in 154 isolates, mef(A) gene in 5 isolates, and both genes in one strain. The phenotype seems to be well correlated to the genotyping result except for strain harboring both resistance determinants. Molecular typing of isolates harboring mef(A) gene performed by pulsed-field gel electrophoresis (PFGE) after restriction by SmaI shows these strains to be epidemiologically unrelated. Our results show the predominance of the erm(B) gene in erythromycin resistant S. pneumoniae isolates. mef(A)-mediated resistance is effective in Southern France (3.7%) but this rate is the lowest published from European countries. Deux principaux mécanismes de résistance aux macrolides sont décrits chez S. pneumoniae : la méthylation de la sous-unité 23S ribosomale à l'origine du phénotype MLS B et un système d'efflux actif déterminant le phénotype M. Ils sont respectivement dus à l'expression des gènes erm(B) et mef(A). Des études de distribution de ces deux gènes ont montré une prédominance du gène mef(A) aux États-Unis et au Canada. En Europe, des publications récentes font état de la présence du gène mef(A) chez environ 10 % des souches, le gène erm(B) restant le plus impliqué. Nous avons étudié 160 souches de pneumocoque de sensibilité diminuée à la pénicilline résistantes à l'érythromycine. L'étude phénotypique a été réalisée par la méthode de diffusion en gélose : 155 souches présentaient un phénotype MLS B et cinq un phénotype M. L'a