Prevalence and Mechanisms of Erythromycin Resistance in Group A and Group B Streptococcus : Implications for Reporting Susceptibility Results

Abstract

Increased rates of erythromycin resistance among group B Streptococcus (GBS) and group A Streptococcus (GAS) have been reported. Cross-resistance to clindamycin may be present, depending on the mechanism of resistance. We determined the prevalence of macrolide-resistant determinants in GBS and GAS isolates to guide the laboratory reporting of erythromycin and clindamycin susceptibility. Susceptibilities were determined by the disk diffusion and broth microdilution methods. Inducible and constitutive resistance to clindamycin was determined by the double-disk diffusion method. The presence of the ermTR, ermB, and mefA genes was confirmed by PCR. Of the 338 GBS isolates, 55 (17%) were resistant to erythromycin, whereas 26 (8%) were resistant to clindamycin. The erm methylase gene was identified in 48 isolates, 22 of which had inducible resistance to clindamycin and 26 of which had constitutive resistance to clindamycin. The remaining seven resistant isolates had mefA. Of the 593 GAS isolates, 49 (8%) and 6 (1%) isolates were resistant to erythromycin and clindamycin, respectively. Erythromycin resistance was due to mefA in 33 isolates, whereas 14 isolates had erm-mediated resistance (9 isolates had inducible resistance and 5 isolates had constitutive resistance). In our population, erythromycin resistance in GAS was predominantly mediated by mefA and erythromycin resistance in GBS was predominantly mediated by erm. Regional differences in mechanisms of resistance need to be taken into consideration when deciding whether to report clindamycin susceptibility results on the basis of in vitro test results. Testing by the double-disk diffusion method would be an approach that could be used to address this issue, especially for GAS.In Canada, as in other regions of North America and Europe, the rates of erythromycin resistance among isolates of the group A Streptococcus (GAS; Streptococcus pyogenes) and the group B Streptococcus (GBS; Streptococcus agalactiae) have been increasing (1,8,16). In Ontario, Canada, the rate of erythromycin resistance among GBS isolates has increased from 5 to 13% over a period of 3 years (4). For GAS isolates it has increased from 2 to 14% over 4 years (12). In the United States, the rates of erythromycin resistance among GBS isolates increased from 12 to 20% between 1990 and 2000 (16). Despite these documented increases, there are geographic variations in resistance rates and the prevalence of resistance mechanisms (11). In one study, the rates of macrolide resistance among GAS isolates varied from 9% in large urban settings to 0% in rural areas, with an overall average of 4.6% (23).Resistance to erythromycin in streptococci is mediated by two major mechanisms. Drug efflux, also referred to as the M phenotype, is encoded by the mefA gene and results in lowlevel resistance to erythromycin but not clindamycin. Resistance may also be due to methylation of the ribosomal drug binding site, which mediates resistance to macrolides, lincosamides, and streptogramin group B (MLS B ). Methylases are e...

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference

“…In Belgium, as determined by the National Reference Centre for GBS, macrolide resistance increased from 10.4% in the early 2000s to 33% among invasive strains isolated from 2008 to 2011 [59]. These figures are consistent with similar reports from Europe [61][62][63][64][65], North America [60,[66][67][68][69][70], and Asia [71,72], except some surveillance studies in Sweden reported 510% [73], thus showing some geographical differences. Different mechanisms account for the acquired resistance to macrolides in streptococci [74].…”

Phenotypic and Genotypic Characterization of Group B Streptococcal Isolates in Southern Brazil

“…This can be regarded as a low rate of incidence compared to incidence data from Asia, Europe, the United States, and Canada (6,16,24,40,42); but similar results were also found in other Latin American and Nordic countries (18, 23, 35, 36, 37). This could be attributed to the more intense clinical use of these antibiotics in Asia, Europe, the United States, and Canada.…”

“…Erythromycin and clindamycin are recommended when risks of anaphylaxis or therapeutic failure are present. However, resistance to erythromycin and clindamycin has increased in many countries in North America (2,6,16,40), Europe (21,22,42,45), and Asia (24) but not in Brazil (18,50) and other Latin American countries (23,35,36). Such a resistance profile is mainly due to two mechanisms: a methylasemediated target site modification and an active efflux pump (53).…”

Distribution of Serotypes and Antimicrobial Resistance Genes among Streptococcus agalactiae Isolates from Bovine and Human Hosts

“…In addition, many S. agalactiae isolates carrying ermTR have been shown to display an inducible macrolides, lincosamides, and streptogramin B resistance, which can only be detected by a double-disk diffusion test, possibly explaining why ermTR-positive isolates tested here were clindamycin sensitive by single-disk testing (15). Importantly, ermB-positive bovine isolates represented a different ribotype than ermB-positive human isolates, indicating a different clonal origin of human and bovine ermB-positive isolates, possibly through horizontal gene transfer either between S. agalactiae or another closely related organism, e.g., Streptococcus pyogenes, which was previously shown to carry ermB (16).…”