The prevalence of Staphylococcus aureus 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 S. aureus. In the current study, 126 inducible methicillin-resistant S. aureus (MRSA) (n = 106) and methicillin-sensitive S. aureus (MSSA) (n = 20) isolates were characterized by in vitro susceptibility analysis, resistance and virulence encoding gene distribution, phenotypic and genotypic analysis of biofilm formation, prophage typing, S. aureus protein A locus (spa) typing, staphylocoagulase (SC) typing, staphylococcal cassette chromosome mec (SCCmec) 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 spa types, 7 coagulase types, 9 prophage types, 3 agr types (no agr IV), and 9 clonal complexes (CCs) were identified in this study. The prevalence of the inducible MLSB (iMLSB) S. aureus 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-SCCmec IV/t008 (n = 4), ST5-SCCmec IV/t002 (n = 4), ST239-SCCmec III/t631 (n = 2), and ST8-SCCmec IV/t064 (n = 2) clones, whereas low-level mupirocin-resistant strains belonged to ST15-SCCmec IV/t084 (n = 5), ST239-SCCmec III/t860 (n = 3), and ST22-SCCmec IV/t790 (n = 3) clones. All the fusidic acid-resistant iMLSB isolates were MRSA and belonged to ST15-SCCmec IV/t084 (n = 2), ST239-SCCmec III/t030 (n = 2), ST1-SCCmec V/t6811 (n = 1), ST80-SCCmec IV/t044 (n = 1), and ST59-SCCmec IV/t437 (n = 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 S. aureus isolates in Iran that identifies predominant clones and treatment options for iMLSB S. aureus-related infections.

Department of Critical Care and Anesthesiology Imam Hossein Hospital Shahid Beheshti University of Medical Sciences Tehran Iran

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Department of Hygiene School of Medicine Sapporo Medical University Sapporo Japan

Department of Internal Medicine Shahid Beheshti University of Medical Sciences Tehran Iran

Department of Microbiology School of Medicine Alborz University of Medical Sciences Karaj Iran

Department of Microbiology School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran

Department of Mycology Pasteur Institute of Iran Tehran Iran

Department of Virology Pasteur Institute of Iran Tehran Iran

School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran

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Abbasi-Montazeri E., Khosravi A. D., Feizabadi M. M., Goodarzi H., Khoramrooz S. S., Mirzaii M., et al. (2013). The prevalence of methicillin resistant PubMed DOI

Abimanyu N., Murugesan S., Krishnan P. (2012). Emergence of methicillin-resistant PubMed DOI PMC

Adhikari R., Shrestha S., Barakoti A., Amatya R. (2017). Inducible clindamycin and methicillin resistant PubMed DOI PMC

Afrough P., Pourmand M. R., Sarajian A. A., Saki M., Saremy S. (2013). Molecular investigation of

Aqel A., Alzoubi H., Al-Zereini W. (2017). Prevalence of inducible clindamycin resistance in methicillin-resistant PubMed DOI

Aqel A., Ibrahim A., Shehabi A. (2012). Rare occurrence of mupirocin resistance among clinical Staphylococcus isolates in Jordan. PubMed DOI

Arciola C. R., Campoccia D., Gamberini S., Cervellati M., Donati E., Montanaro L. J. B. (2002). Detection of slime production by means of an optimised Congo red agar plate test based on a colourimetric scale in PubMed DOI

Aydin A., Sudagidan M., Muratoglu K. (2011). Prevalence of staphylococcal enterotoxins, toxin genes and genetic-relatedness of foodborne PubMed DOI

Azimian A., Havaei S. A., Ghazvini K., Khosrojerdi M., Naderi M., Samiee S. M. (2014). Isolation of PVL/ACME-positive, community acquired, methicillin-resistant

Boswihi S. S., Udo E. E., Al-Sweih N. (2016). Shifts in the clonal distribution of methicillin-resistant PubMed DOI PMC

Bottega A., Rodrigues M. D. A., Carvalho F. A., Wagner T. F., Leal I. A. S., Santos S. O. D., et al. (2014). Evaluation of constitutive and inducible resistance to clindamycin in clinical samples of PubMed DOI

Boye K., Bartels M. D., Andersen I. S., Moeller J. A., Westh H. (2007). A new multiplex PCR for easy screening of methicillin-resistant PubMed DOI

Castanheira M., Watters A. A., Bell J. M., Turnidge J. D., Jones R. N. (2010a). Fusidic acid resistance rates and prevalence of resistance mechanisms among PubMed DOI PMC

Castanheira M., Watters A. A., Mendes R. E., Farrell D. J., Jones R. N. (2010b). Occurrence and molecular characterization of fusidic acid resistance mechanisms among PubMed DOI

Chamon R. C., Iorio N. L. P., da Silva Ribeiro S., Cavalcante F. S., dos Santos K. R. N. (2015). Molecular characterization of PubMed DOI

Chavez-Bueno S., Bozdogan B., Katz K., Bowlware K. L., Cushion N., Cavuoti D., et al. (2005). Inducible clindamycin resistance and molecular epidemiologic trends of pediatric community-acquired methicillin-resistant PubMed DOI PMC

Dadashi M., Nasiri M. J., Fallah F., Owlia P., Hajikhani B., Emaneini M., et al. (2018). Methicillin-resistant PubMed DOI

Deotale V., Mendiratta D., Raut U., Narang P. (2010). Inducible clindamycin resistance in PubMed DOI

Desroches M., Potier J., Laurent F., Bourrel A.-S., Doucet-Populaire F., Decousser J.-W., et al. (2013). Prevalence of mupirocin resistance among invasive coagulase-negative staphylococci and methicillin-resistant PubMed DOI

Diep B. A., Stone G. G., Basuino L., Graber C. J., Miller A., des Etages S. A., et al. (2008). The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant PubMed DOI

Enright M. C., Day N. P., Davies C. E., Peacock S. J., Spratt B. G. (2000). Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of PubMed PMC

Fossum A., Bukholm G. (2006). Increased incidence of methicillin-resistant PubMed DOI

Gad G. F. M., El-Feky M. A., El-Rehewy M. S., Hassan M. A., Abolella H., El-Baky R. M. A. (2009). Detection of icaA, icaD genes and biofilm production by PubMed DOI

Gilot P., Lina G., Cochard T., Poutrel B. (2002). Analysis of the genetic variability of genes encoding the RNA III-activating components Agr and TRAP in a population of PubMed DOI PMC

González-Domínguez M., Seral C., Potel C., Sáenz Y., Álvarez M., Torres C., et al. (2016). Genotypic and phenotypic characterization of methicillin-resistant PubMed DOI

Gordon R. J., Lowy F. D. (2008). Pathogenesis of methicillin-resistant PubMed DOI PMC

Goudarzi M., Bahramian M., Tabrizi M. S., Udo E. E., Figueiredo A. M. S., Fazeli M., et al. (2017). Genetic diversity of methicillin resistant PubMed DOI

Goudarzi M., Goudarzi H., Figueiredo A. M. S., Udo E. E., Fazeli M., Asadzadeh M., et al. (2016a). Molecular characterization of methicillin resistant PubMed DOI PMC

Goudarzi M., Seyedjavadi S. S., Azad M., Goudarzi H., Azimi H. (2016b). Distribution of spa types, integrons and associated gene cassettes in

Gould I. M., David M. Z., Esposito S., Garau J., Lina G., Mazzei T., et al. (2012). New insights into meticillin-resistant PubMed DOI

Grundmann H., Schouls L. M., Aanensen D. M., Pluister G. N., Tami A., Chlebowicz M., et al. (2014). The dynamic changes of dominant clones of PubMed DOI

Harmsen D., Claus H., Witte W., Rothgänger J., Claus H., Turnwald D., et al. (2003). Typing of methicillin-resistant PubMed DOI PMC

Hirose M., Kobayashi N., Ghosh S., Paul S. K., Shen T., Urushibara N., et al. (2010). Identification of Staphylocoagulase Genotypes I-X and Discrimination of Type IV and V Subtypes by Multiplex PCR Assay for Clinical Isolates of PubMed

Holmes A., Ganner M., McGuane S., Pitt T., Cookson B., Kearns A. (2005). PubMed DOI PMC

Ilczyszyn W. M., Sabat A. J., Akkerboom V., Szkarlat A., Klepacka J., Sowa-Sierant I., et al. (2016). Clonal structure and characterization of PubMed DOI PMC

Imanifooladi A., Sattari M., Peerayeh S. N., Hassan Z., Hossainidoust S. (2007). Detection the PubMed

Janwithayanuchit I., Ngam-Ululert S., Paungmoung P., Rangsipanuratn W. (2006). Epidemiologic study of methicillin-resistant DOI

Kahánková J., Pantůček R., Goerke C., Růžičková V., Holochová P., Doškař J. (2010). Multilocus PCR typing strategy for differentiation of PubMed DOI

Khashei R., Malekzadegan Y., Sedigh Ebrahim-Saraie H., Razavi Z. (2018). Phenotypic and genotypic characterization of macrolide, lincosamide and streptogramin B resistance among clinical isolates of staphylococci in southwest of Iran. PubMed DOI PMC

Lewis J. S., Jorgensen J. H. (2005). Inducible clindamycin resistance in staphylococci: should clinicians and microbiologists be concerned? PubMed DOI

Li J., Wang L., Ip M., Sun M., Sun J., Huang G., et al. (2013). Molecular and clinical characteristics of clonal complex 59 methicillin-resistant PubMed DOI PMC

Li S., Sun S., Yang C., Chen H., Yin Y., Li H., et al. (2018). The changing pattern of population structure of PubMed DOI PMC

Liang B., Mai J., Liu Y., Huang Y., Zhong H., Xie Y., et al. (2018). Prevalence and Characterization of PubMed DOI PMC

Luther M. K., Parente D. M., Caffrey A. R., Daffinee K. E., Lopes V. V., Martin E. T., et al. (2018). Clinical and genetic risk factors for biofilm-forming PubMed DOI PMC

Mathur T., Singhal S., Khan S., Upadhyay D., Fatma T., Rattan A. (2006). Detection of biofilm formation among the clinical isolates of staphylococci: an evaluation of three different screening methods. PubMed DOI

Memariani M., Pourmand M., Shirazi M., Dallal M., Abdossamadi Z., Mardani N. (2009). The importance of inducible clindamycin resistance in enterotoxin positive

Mirzaee M., Najar-Peerayeh S., Behmanesh M., Forouzandeh-Moghadam M., Ghasemian A.-M. (2014). Detection of intracellular adhesion (ica) gene and biofilm formation

Monday S. R., Bohach G. A. (1999). Use of multiplex PCR to detect classical and newly described pyrogenic toxin genes in staphylococcal isolates. PubMed PMC

Monecke S., Coombs G., Shore A. C., Coleman D. C., Akpaka P., Borg M., et al. (2011). A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant PubMed DOI PMC

Nemati M., Hermans K., Devriese L. A., Maes D., Haesebrouck F. (2009). Screening of genes encoding adhesion factors and biofilm formation in PubMed DOI

Nezhad R. R., Meybodi S. M., Rezaee R., Goudarzi M., Fazeli M. (2017). Molecular characterization and resistance profile of methicillin resistant DOI

Omar N. Y., Ali H. A. S., Harfoush R. A. H., El Khayat E. H. (2014). Molecular typing of methicillin resistant PubMed DOI PMC

Pantosti A., Sanchini A., Monaco M. (2007). Mechanisms of antibiotic resistance in PubMed DOI

Pantůček R., Doškař J., Růžičková V., Kašpárek P., Oráčová E., Kvardova V., et al. (2004). Identification of bacteriophage types and their carriage in PubMed DOI

Patel M., Waites K. B., Moser S. A., Cloud G. A., Hoesley C. J. (2006). Prevalence of inducible clindamycin resistance among community-and hospital-associated PubMed DOI PMC

Petinaki E., Spiliopoulou I., Kontos F., Maniati M., Bersos Z., Stakias N., et al. (2004). Clonal dissemination of mupirocin-resistant staphylococci in Greek hospitals. PubMed DOI

Rahimi F., Bouzari M., Katouli M., Pourshafie M. R. (2012). Prophage and antibiotic resistance profiles of methicillin-resistant PubMed DOI

Rolo J., Miragaia M., Turlej-Rogacka A., Empel J., Bouchami O., Faria N. A., et al. (2012). High genetic diversity among community-associated PubMed DOI PMC

Samie A., Shivambu N. (2011). Biofilm production and antibiotic susceptibility profiles of DOI

Shahsavan S., Emaneini M., Khoshgnab B. N., Khoramian B., Asadollahi P., Aligholi M., et al. (2012). A high prevalence of mupirocin and macrolide resistance determinant among PubMed DOI

Shore A. C., Tecklenborg S. C., Brennan G. I., Ehricht R., Monecke S., Coleman D. C. (2014). Panton-Valentine leukocidin-positive PubMed DOI PMC

Song Y., Du X., Li T., Zhu Y., Li M. (2013). Phenotypic and molecular characterization of PubMed DOI

Stepanović S., Vuković D., Hola V., Bonaventura G. D., Djukić S., Ćirković I., et al. (2007). Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci. PubMed DOI

Wang L., Liu Y., Yang Y., Huang G., Wang C., Deng L., et al. (2012). Multidrug-resistant clones of community-associated meticillin-resistant PubMed DOI

Wang L., Yu F., Yang L., Li Q., Zeng X. Z., Xu Y. (2010). Prevalence of virulence genes and biofilm formation among

Williamson D. A., Roberts S. A., Ritchie S. R., Coombs G. W., Fraser J. D., Heffernan H. (2013). Clinical and molecular epidemiology of methicillin-resistant PubMed DOI PMC

Workman M., Nigro O. D., Steward G. F. (2006). Identification of prophagein Hawaiian coastal water isolate of

Yousefi M., Pourmand M. R., Fallah F., Hashemi A., Mashhadi R., Nazari-Alam A. (2016). Characterization of PubMed PMC

Yu F., Liu Y., Lu C., Jinnan L., Qi X., Ding Y., et al. (2015). Dissemination of fusidic acid resistance among PubMed DOI PMC

Yun H.-J., Lee S. W., Yoon G. M., Kim S. Y., Choi S., Lee Y. S., et al. (2003). Prevalence and mechanisms of low-and high-level mupirocin resistance in staphylococci isolated from a Korean hospital. PubMed DOI