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Infection Control & Hospital Epidemiology (2018), 39, 1412–1418 doi:10.1017/ice.2018.239


Original Article


Whole-genome sequencing for methicillin-resistant Staphylococcus aureus (MRSA) outbreak investigation in a neonatal intensive care unit


Theresa Madigan MD1, Scott A. Cunningham MS2, Robin Patel MD2,3, Kerryl E. Greenwood-Quaintance MS2, Jean E. Barth MPH, RN4, Priya Sampathkumar MD3,4, Nicolynn C. Cole2, Peggy C. Kohner2, Christopher E. Colby MD5, Garth F. Asay MD5, Jennifer L. Fang MD5, Christine A. Baker MSN, RN5,6, Angela L. Heinrich MSN, RN5,6, Kelly A. Fjerstad MBA/HCM, MSN, RN, NE-BC5,6,Maria J. Lujero RN5,6, Nicholas Chia PhD7,8,PatricioR.Jeraldo PhD7,8,


Heidi Nelson MD7,8 and W. Charles Huskins MD1,4 1Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, 2Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Minnesota, 3Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, 4Infection Prevention and Control, Mayo Clinic, Rochester, Minnesota, 5Division of Neonatal Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, 6Department of Nursing, Mayo Clinic, Rochester, Minnesota, 7Department of Surgery, Mayo Clinic, Rochester, Minnesota and 8Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota


Abstract


Objective: To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation. Design: Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017). Setting: Single-center level IV NICU. Patients: NICU infants and healthcare workers (HCWs). Methods: Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU. Results: We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions. Conclusion: We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.


(Received 22 June 2018; accepted 26 August 2018; electronically published October 4, 2018)


Methicillin-resistant Staphylococcus aureus (MRSA) infections in neonatal intensive care unit (NICU) infants are associated with significant morbidity, prolonged hospital stays, and increased healthcare costs.1,2 Colonization with MRSA is an important risk factor for development of infection, as colonized infants are 24- fold more likely to develop infection during their hospitalization


Author for correspondence: Robin Patel MD, Division of Clinical Microbiology,


Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. E-mail: patel.robin@mayo.edu PREVIOUS PRESENTATION: The results of this project were presented in part at the


ASM Microbe 2017 meeting on June 5, 2017, in New Orleans, Louisiana, and at the Pediatric Academic Societies meeting on May 6, 2018, in Toronto, Canada. Cite this article: Madigan T, et al. (2018). Whole-genome sequencing for methicillin-


resistant Staphylococcus aureus (MRSA) outbreak investigation in a neonatal intensive care unit. Infection Control&Hospital Epidemiology 2018, 39, 1412–1418. doi: 10.1017/ice.2018.239


© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved.


than those who are not colonized.3 In more than 90% of cases, infection occurs with the strain that previously colonized the infant,4 demonstrating the importance of MRSA surveillance and interventions to prevent its spread. Guidelines for the management of MRSA outbreaks in


NICUs recommend use of molecular analysis to assess related- ness of strains found in patients, healthcare workers (HCWs), and the environment.5 This information is important because it allows discrimination between sporadic cases and those linked to outbreaks, thereby helping identify potential reservoirs and routes of transmission. Historically, several molecular methods have been used for strain typing: pulsed-field gel electrophoresis (PFGE), surface protein A sequence typing (spa typing), and multilocus sequence typing (MLST).6 Recent studies have demonstrated that typing based on whole-genome sequencing


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