Emerging variants of methicillin-resistant Staphylococcus aureus genotypes in Kuwait hospitals

RESEARCH ARTICLE Emerging variants of methicillin-resistant Staphylococcus aureus genotypes in Kuwait hospitals Samar S. Boswihi1, Edet E. Udo1*, Stefan Monecke2,3,4, Bindu Mathew1, Bobby Noronha1, Tina Verghese1, Sajida B. Tappa1 1 Department of Microbiology, Faculty of Medicine, Kuwait University. Jabriya, Kuwait, 2 Alere Technologies GmbH, Jena, Germany, 3 InfectoGnostics Research Campus, Jena, Germany, 4 Institute for Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 * Abstract Background OPEN ACCESS Citation: Boswihi SS, Udo EE, Monecke S, Mathew B, Noronha B, Verghese T, et al. (2018) Emerging variants of methicillin-resistant Staphylococcus aureus genotypes in Kuwait hospitals. PLoS ONE 13(4): e0195933. https://doi.org/10.1371/journal. pone.0195933 Editor: Herminia de Lencastre, Rockefeller University, UNITED STATES Received: January 4, 2018 Frequent changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) occurring worldwide demand regular surveillance to study their composition and distribution in healthcare facilities. We investigated the genotypic characteristics of MRSA obtained in Kuwait hospitals to better understand their clonal distribution. Materials and methods A total of 1,327 MRSA isolates obtained from clinical samples in 13 Kuwait hospitals from 1 January to 31 December 2016 were investigated using antibiogram, SCCmec typing, spa typing and DNA microarray. Accepted: April 3, 2018 Published: April 18, 2018 Results Copyright: © 2018 Boswihi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The isolates belonged to six SCCmec types with the majority belonging to type IV (658; 49.5%) and type V (355; 26.7%). Two hundred and sixty-one spa types were identified with spa types t688, t304, t860, t127, t044, t311, t002, t223, t267, t019, t3841, t005, t084, t852, and t657 constituting 51.0% (n = 677) of the isolates. Among the 1,327 MRSA isolates, 102 (7.68%) isolates were identified as novel variants of internationally recognized MRSA clones. These 102 isolates were investigated further and belonged to 14 clonal complexes (CCs) with CC361 (32; 32.3%), CC30 (15; 14.7%), CC22 (13; 12.7%) and CC1 (11, 10.7%) as the dominant CCs. Eighty-one (79.4%) of the novel isolates harbored SCCmec IV or V+fusC composite genetic elements. Four isolates (3.9%) harbored unusual combinations of ccr and mec complexes comprising of CC6-MRSA [IV+fusC+ccrC], CC97-MRSA [V/ VT+fusC+ccrAB2], CC121-MRSA [V/VT+fusC+ccrB4] and CC1-MRSA-pseudoSCCmec [class B mec+fusc+ccrAB1]. Forty-six (45.1%) of these isolates were positive for PVL and 89 (87.2%) were resistant to fusidic acid mediated by fusC. Data Availability Statement: All relevant data are within the paper. Funding: This work was funded by Research Sector, Kuwait University Grant no. YM02/12 to SSB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. PLOS ONE | https://doi.org/10.1371/journal.pone.0195933 April 18, 2018 1 / 13 Novel variants of MRSA genotypes in Kuwait Conclusions The study showed the emergence of novel variants of previously recognized MRSA genotypes with unusual genetic characteristics including high prevalence of PVL and fusidic acid resistance in Kuwait hospitals. This has added to the dynamic lists of known variations in MRSA genomes which can impose serious challenges for infection control and treatment of MRSA infections. Background Methicillin-resistant Staphylococcus aureus (MRSA) can spread rapidly in hospitals and other healthcare settings resulting in an increased workload for healthcare workers and economic burden [1]. Prior to the 1990s, MRSA was reported mostly in elderly patients admitted to healthcare facilities with previous history of hospitalization and antibiotic treatment. However, beginning in the early 1990s MRSA strains were reported in patients in the community with no previous history of admission to healthcare facilities in Western Australia and elsewhere [2, 3]. These strains were different from the multiply-resistant epidemic MRSA (EMRSA) that were prevalent at the time by being susceptible to most non -beta-lactam antibiotics and were subsequently designated non-multiresistant MRSA or community-originated / communityassociated MRSA (CA-MRSA) [3, 4]. One of the early CA-MRSA strains reported belonged to ST30, a clone known as the Southwest Pacific clone (SWP) [5]. Since then, several CA-MRSA belonging to diverse clones have been reported worldwide [6, 7]. The composition of MRSA clones is changing in different healthcare facilities in different countries. For example, the CA-MRSA clone, ST30-MRSA-IV replaced the multiresistant clone, ST239-MRSA-III, in Singapore and Malaysian hospitals [8]. Studies from the United Arab Emirates [9], Portugal [10], India [11] and Germany [12] have also reported the replacement of ST239-III-MRSA by CA-MRSA clones. Similarly, ST22-MRSA-IV and ST772-MRSA-V have replaced ST239-MRSA-III as the dominant clones in Indian hospitals [13]. Furthermore, a recent study which investigated changes in the epidemiology of MRSA strains from 1992 to 2010 in Kuwait hospitals revealed that most of the MRSA strains obtained in the 1990s belonged to the well-studied healthcare -associated MRSA genotype, ST239MRSA-III. However, since 2010 the prevalence of ST239-MRSA-III strains declined accompanied by an increase in the number and diversity of CA-MRSA clones including ST772, a clone widely reported in India and Bangladesh and in other countries [14]. In furtherance of the need to obtain current data on the epidemiology of MRSA strains in Kuwait hospitals, MRSA obtained from1 January to 31 December 2016 were investigated using a combination of molecular typing techniques. Results of molecular typing revealed the presence of a mixed population of MRSA composed of internationally recognized clones and variants of those clones that were not previously reported in Kuwait. The purpose of this study was to characterize the novel variants of these MRSA clones for antimicrobial resistance and carriage of virulence-related genes. Materials and methods Bacterial strains The MRSA isolates used in this study were collected as part of routine diagnostic microbiology investigations and later submitted to the MRSA Reference Laboratory for molecular typing. In total, 1,327 MRSA isolates collected from 13 different hospitals in Kuwait from 1 January to 31 PLOS ONE | https://doi.org/10.1371/journal.pone.0195933 April 18, 2018 2 / 13 Novel variants of MRSA genotypes in Kuwait December 2016 were investigated. I (...truncated)