Staphylococcus aureus from ocular and otolaryngology infections are frequently resistant to clinically important antibiotics and are associated with lineages of community and hospital origins

RESEARCH ARTICLE Staphylococcus aureus from ocular and otolaryngology infections are frequently resistant to clinically important antibiotics and are associated with lineages of community and hospital origins a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Wurster JI, Bispo PJM, Van Tyne D, Cadorette JJ, Boody R, Gilmore MS (2018) Staphylococcus aureus from ocular and otolaryngology infections are frequently resistant to clinically important antibiotics and are associated with lineages of community and hospital origins. PLoS ONE 13(12): e0208518. https://doi.org/ 10.1371/journal.pone.0208518 Editor: Herminia de Lencastre, Rockefeller University, UNITED STATES Received: July 24, 2018 Accepted: November 19, 2018 Published: December 6, 2018 Copyright: © 2018 Wurster 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. Data Availability Statement: The minimal underlying data set is available in a Supporting Information file on this article. Funding: Portions of this project were supported by NIH grants EY024285, Molecular Basis for Ocular Surface Tropism in Conjunctivitis, and AI083214, which funds the Harvard-wide Program on Antibiotic Resistance. P.B. was supported by a grant from the Coordenação de Aperfeiçoamentio Jenna I. Wurster1☯¤a, Paulo J. M. Bispo ID1☯*, Daria Van Tyne1,2¤b, James J. Cadorette3, Rick Boody3, Michael S. Gilmore1,2* 1 Infectious Diseases Institute, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America, 2 Department of Microbiology and Immunobiology, Harvard Medical School, Boston Massachusetts, United States of America, 3 Henry Whittier Porter Bacteriology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America ☯ These authors contributed equally to this work. ¤a Current address: Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, United States of America ¤b Current address: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Philadelphia, PA, United States of America * (MSG); (PB) Abstract Staphylococcus aureus is an important human pathogen that causes serious antibioticresistant infections. Its population structure is marked by the appearance and dissemination of successful lineages across different settings. To begin understanding the population structure of S. aureus causing ocular and otolaryngology infections, we characterized 262 isolates by antimicrobial sensitivity testing and multilocus sequence typing (MLST). Methicillin-resistant S. aureus were subjected to SCCmec typing and Panton-Valentine leukocidin (PVL) screening. Although we detected a high level of genetic diversity among methicillinsensitive (MSSA) isolates, (63 sequence types—STs), the population was dominated by five lineages: ST30, ST5, ST8, ST15 and ST97. Resistance to penicillin, erythromycin and clindamycin was common among the major MSSA lineages, with fluctuations markedly impacted by genetic background. Isolates belonging to the predominant lineage, ST30, displayed high rates of resistance to penicillin (100%), erythromycin (71%), and clindamycin (63%). Overall, 21% of the isolates were methicillin-resistant (MRSA), with an apparent enrichment among otitis and orbital cellulitis isolates (>40%). MRSA isolates belonged to 14 STs grouped in 5 clonal complexes (CC), however, CC5 (56.1%) and CC8 (38.6%) dominated the population. Most CC5 strains were SCCmec type II, and resembled the hospitaladapted USA100 clone. CC8 strains were SCCmec type IV, and 86% were positive for the PVL toxin, common features of the community-acquired clone USA300. CC5 strains harboring a SCCmec type IV, typical for the USA800 clone, comprised 15.5% of the population. USA100 strains were highly resistant to clindamycin, erythromycin and levofloxacin (100%), PLOS ONE | https://doi.org/10.1371/journal.pone.0208518 December 6, 2018 1 / 15 Molecular epidemiology of S. aureus ocular and otolaryngology infections de Pessoal de Nı́vel Superior, Brazil (CAPES #9775-13-7), and D.V.T. was supported by NIH grant AI109855. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Competing interests: The authors have declared that no competing interests exist. while USA300 strains were frequently resistant to erythromycin (89%) but displayed lower rates of resistance to levofloxacin (39%) and clindamycin (17%). Our data demonstrate that the ocular and otolaryngology S. aureus populations are composed of strains that are commonly resistant to clinically relevant antibiotics, and are associated with the major epidemic clonal complexes of both community and hospital origins. Introduction Staphylococcus aureus is a prevalent community-acquired pathogen as well as a leading cause of nosocomial infection [1, 2]. The global success of S. aureus is, in part, due to its ability to efficiently colonize the respiratory system and other epithelial and mucosal surfaces in healthy individuals, which serve as staging grounds for dissemination and infection [3, 4]. Additionally, the ability of S. aureus to develop resistance to multiple antibiotic classes promotes the selection and expansion of epidemic antibiotic-resistant lineages that can thrive in both the community and hospital settings, posing a serious threat to public health [5]. Communityacquired methicillin-resistant S. aureus (CA-MRSA), which cause predominantly skin and soft tissue infections, have rapidly spread throughout the United States following the first reported cases in the late 1990s [6]. MRSA have also become leading causes of clinically relevant infections of the eye [7, 8] and ear [9], which develop primarily in patients within the community setting and can result in drastic vision loss and poor patient outcomes [10]. Numerous comprehensive surveillance studies have performed genetic characterization of S. aureus isolates in the USA, however these have been primarily focused on systemic or skin and soft tissue infections [11–14]. Antimicrobial resistance surveillance studies of ocular and otolaryngology isolates have been performed previously on a local [15–18] or nationwide scale [7, 19], but molecular typing to characterize population structure is not a common component of those studies. To fill this gap, we sought to investigate the molecular epidemiology of S. aureus isolated from eye, ear, and sinus infections treated at a tertiary care center in New England. We used antimicrobial resistance testing and sequence typing to determine the population structure of the S. aureus reservoir in this setting, and to determine whether the major genetic l (...truncated)