The rare genes related to resistance to macrolide-lincosamide and streptogramin B group antibiotics among coagulase-negative staphylococci

Macrolide-lincosamide-streptogramin B (MLSB) group antibiotics are recommended as first choice in the treatment of staphylococcal infections. All of those drugs bind to the 50S subunit of bacterial ribosomes, thus cross-resistance is a major concern in this group of drugs. The mechanisms associated to resistance are (a) ribosomal methylation due to the methylases encoded by erm genes, (b) active drug efflux due to msrA, msrB, vga, vgb gene activity, (c) enzymatic inactivation of the drug due to the activity of linA, vat, vatB genes. While the most common resistance genes are ermA, ermB, ermC, msrA and msrB genes; linA, vga, vgb, vat and vatB genes have also been found in some studies. In this study it was aimed to investigate the presence of the rare MLSB resistance genes and their coexistence with erm and msr genes in 454 clinical isolates of coagulase-negative staphylococci (CNS). Of them 46.5% (n= 211) were S.hominis, 30.8% (n= 140) were S.epidermidis, 12.1% (n= 55) were S.haemolyticus, 3.5% (n= 16) were S.warnerii and 7% (n= 32) were the other coagulase-negative staphylococcal species. Resistance phenotypes were determined by using D-test method according to the recommendation of Clinical and Laboratory Standards Institute (CLSI). With the D-test 107 (23.6%) strains were determined as M phenotype (resistant to erythromycin and inducible clindamycin resistance was not detected), 92 (20.3%) were iMLSB phenotype (inducible clindamycin resistance was detected by the D-test) and 110 (24.2%) were cMLSB phenotype (constitutive erythromycin and clindamycin resistance was detected). linA, vga, vgb, vat, vatB, ermA, ermB, ermC, msrA, msrB genes were investigated by polymerase chain reaction in all strains showing iMLSB (n= 92) and cMLSB (n= 110) phenotypes and 46 randomly selected strains among 107 strains exhibiting the M phenotype. linA gene was found in 91 (20%) strains as single gene or in combination with erm or msr genes, and vga gene was found in 19 (4.2%) strains. linA gene was found in 52% of iMLSB phenotype, in 26% of cMLSB phenotype and 13% of M phenotype while vga gene was found in 5.4% of iMLSB phenotype, in 12% of cMLSB phenotype and in 0.9% of M phenotype. The most common resistance gene among iMLSB and cMLSB phenotypes was ermC (32.6% and 42.7%, respectively), followed by ermC + linA gene combination (31.5% and 14.5%, respectively). The most frequent gene combination was msrA and msrB in M phenotype (34.8%) and it was followed by a combination of