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Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common
J Sutcliffe1, A Tait-Kamradt, L Wondrack
1Department of Infectious Diseases, Pfizer, Inc., Groton, Connecticut 06340, USA.
Abstract:
Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice.
Insights
Macrolide resistance (M phenotype) is common in Streptococcus strains, showing resistance to macrolides but susceptibility to clindamycin. This suggests an efflux mechanism, impacting antibiotic choice.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Macrolide resistance is a growing concern in bacterial pathogens.
- An unusual resistance pattern, termed M resistance, has been observed in Streptococcus species.
Purpose of the Study:
- To investigate the prevalence and mechanism of the M resistance phenotype in Streptococcus pneumoniae and Streptococcus pyogenes.
- To understand the implications of M resistance for clinical practice.
Main Methods:
- Phenotypic characterization of macrolide-lincosamide-streptogramin B resistance in clinical isolates.
- Investigation of resistance mechanisms, including target modification and efflux pumps.
- Radiolabeled erythromycin uptake studies.
Main Results:
- The M resistance phenotype was prevalent in collected Streptococcus strains (85% of S. pneumoniae, 75% of S. pyogenes).
- Resistance was not due to target modification or erm methylase.
- Evidence suggests a macrolide efflux determinant, distinct from staphylococcal systems, is responsible.
Conclusions:
- The M resistance phenotype is common in Streptococcus species.
- An efflux mechanism, not target modification, underlies this resistance.
- Findings have significant implications for antibiotic sensitivity testing and therapeutic choices.