[Differentiation of resistance phenotypes among erythromycin-resistant streptococci]

Although macrolide antibiotics have proved to be a valuable alternative to beta-lactam antibiotics in the treatment of respiratory tract infections, resistance to these agents is now becoming established in streptococci, especially among Streptococcus pneumoniae isolates. Of particular concern is the emergence of cross-resistance to 14-, 15- and 16-membered macrolides, licosamides and group B streptogramins (MLSb phenotype). MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype). MLS resistance is mediated by two classes of methylase genes--the conventional erm(B) and recently described erm(A) determinants. A new macrolide efflux mechanism has been described for streptococci, in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14- and 15-membered macrolides, and susceptibility to 16-membered macrolides, lincosamides and streptogramin B. The recognition of the prevalence of M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice. While M resistance is similar in S. pyogenes and S. pneumoniae being mediated by mef(A) and mef(E), respectively, MLS resistance in both species appears to be genotypically and phenotypically more varied. Differentiation of M and MLS phenotypes of erythromycin-resistant strains can be performed using the erythromycin-clindamycin double-disc method (ECDD). Distinguishing not only M resistance but also constitutively or inducibly MLS phenotype by ECDD in S. pyogenes is easily and reliably achieved. Inducible MLS phenotype S. pyogenes strain is genotypically and phenotypically heterogeneous and is further subdivided into three recently described subtypes, iMLS-A, iMLS-B and iMLS-C, by a triple-disk test with erythromycin plus clindamycin and josamycin. While distinguishing M from MLS resistance in S. pneumoniae by ECDD test is easily and reliably achieved, the differentiation between constitutive and inducible MLS resistance is by far more uncertain. The meaning of inducible MLS resistance appears to be different in S. pneumoniae from that in S. pyogenes. In order to easily differentiate, within erythromycin-resistant pneumococci, not only the strains of the M phenotype from those with MLS resistance but also among the latter, cMLS from iMcLS strains, a triple-disk test has been set up by adding a rokitamycin disk to the conventional