Prevalence, Genetic Diversity, and Temporary Shifts of Inducible Clindamycin Resistance Staphylococcus aureus Clones in Tehran, Iran: A Molecular–Epidemiological Analysis From 2013 to 2018

Abstract

The prevalence of <i>Staphylococcus aureus</i> as an aggressive pathogen resistant to multiple antibiotics causing nosocomial and community-acquired infections is increasing with limited therapeutic options. Macrolide-lincosamide streptogramin B (MLSB) family of antibiotics represents an important alternative therapy for staphylococcal infections. This study was conducted over a period of five years from August 2013 to July 2018 to investigate the prevalence and molecular epidemiology in Iran of inducible resistance in <i>S. aureus</i>. In the current study, 126 inducible methicillin-resistant <i>S. aureus</i> (MRSA) (<i>n</i> = 106) and methicillin-sensitive <i>S. aureus</i> (MSSA) (<i>n</i> = 20) isolates were characterized by <i>in vitro</i> susceptibility analysis, resistance and virulence encoding gene distribution, phenotypic and genotypic analysis of biofilm formation, prophage typing, <i>S. aureus</i> protein A locus (<i>spa</i>) typing, staphylocoagulase (SC) typing, staphylococcal cassette chromosome <i>mec</i> (SCC<i>mec</i>) typing, and multilocus sequence typing. Of the 126 isolates, 76 (60.3%) were classified as hospital onset, and 50 (39.7%) were classified as community onset (CO). Biofilm formation was observed in 97 strains (77%). A total of 14 sequence types (STs), 26 <i>spa</i> types, 7 coagulase types, 9 prophage types, 3 <i>agr</i> types (no <i>agr</i> IV), and 9 clonal complexes (CCs) were identified in this study. The prevalence of the inducible MLSB (iMLSB) <i>S. aureus</i> increased from 7.5% (25/335) to 21.7% (38/175) during the study period. The iMLSB MRSA isolates were distributed in nine CCs, whereas the MSSA isolates were less diverse, which mainly belonged to CC22 (7.95%) and CC30 (7.95%). High-level mupirocin-resistant strains belonged to ST85-SCC<i>mec</i> IV/t008 (<i>n</i> = 4), ST5-SCC<i>mec</i> IV/t002 (<i>n</i> = 4), ST239-SCC<i>mec</i> III/t631 (<i>n</i> = 2), and ST8-SCC<i>mec</i> IV/t064 (<i>n</i> = 2) clones, whereas low-level mupirocin-resistant strains belonged to ST15-SCC<i>mec</i> IV/t084 (<i>n</i> = 5), ST239-SCC<i>mec</i> III/t860 (<i>n</i> = 3), and ST22-SCC<i>me</i>c IV/t790 (<i>n</i> = 3) clones. All the fusidic acid-resistant iMLSB isolates were MRSA and belonged to ST15-SCC<i>mec</i> IV/t084 (<i>n</i> = 2), ST239-SCC<i>mec</i> III/t030 (<i>n</i> = 2), ST1-SCC<i>mec</i> V/t6811 (<i>n</i> = 1), ST80-SCC<i>mec</i> IV/t044 (<i>n</i> = 1), and ST59-SCC<i>mec</i> IV/t437 (<i>n</i> = 1). The CC22 that was predominant in 2013-2014 (36% of the isolates) had almost disappeared in 2017-2018, being replaced by the CC8, which represented 39.5% of the 2017-2018 isolates. This is the first description of temporal shifts of iMLSB <i>S. aureus</i> isolates in Iran that identifies predominant clones and treatment options for iMLSB <i>S. aureus</i>-related infections.