Clindamycin is an alternative drug for infections due to Staphylococcus aureus in case of intolerance to penicillins or resistance to methicillin. However, resistance to clindamycin limits the use of this antibiotic.
Two primary mechanisms result in resistance to macrolide antibiotics in staphylococci: macrolide efflux, controlled by the msr(A) gene, and modification of the drug-binding site on the ribosome, controlled by erm (erythromycin ribosome methylation) genes. The efflux mechanism yields inducible resistance to 14-membered (erythromycin, clarithromycin, roxithromycin) and 15-membered (azithromycin) macrolides and type B streptogramins but not to lincosamides (clindamycin and lincomycin). Ribosomal methylation confers cross-resistance to macrolides, lincosamides, and type B streptogramins, the so-called MLSB phenotype. In staphylococci, erm(A) or erm(C) is responsible for this cross-resistance phenotype by controlling the methylation of the 23S rRNA binding site of adenosine 2058 (A2058). Methylation results in impaired binding of the three drug classes that share this residue as a common binding site.
Specialized testing is needed to detect MLS-B resistance, also known as inducible resistance, to clindamycin. In MLS-B bacterial strains, erythromycin induces production of a methylase enzyme, which allows clindamycin resistance to be expressed.
Inducible clindamycin resistance is determined by means of an antibiotic disk diffusion test, called the D-test, which requires overnight incubation of the organism being tested. The clindamycin induction test can be performed on staphylococci and beta-hemolytic streptococci that test resistant to erythromycin and susceptible to clindamycin by routine methods.
Inducible resistance to clindamycin is found in 7-20% of both methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA). Community-acquired MRSA isolates are somewhat more susceptible than hospital-acquired strains. D-testing is of particular importance in community-acquired MRSA infections since oral clindamycin is widely used in therapy.
References
Daurel et al. Differences in Potential for Selection of Clindamycin-Resistant Mutants Between Inducible erm(A) and erm(C) Staphylococcus aureus Genes, J Clin Microbiol.2007;46(2):546-550.
Khursheed M, Sulaiman M, Alhassan AM, Al Awad TH, Ibrahim AE, Wilson G, et al. (2025) Clindamycin-resistant among Staphylococcus aureus: Investigation into phenotypic and genotypic profiles. PLoS One 20(8): e0329467. https://doi.org/10.1371/journal.pone.0329467
How to resolve AdBlock issue?