Jakko van Ingen1, Thomas A Kohl2, Katharina Kranzer3, Barbara Hasse4, Peter M Keller5, Anna Katarzyna Szafrańska6, Doris Hillemann3, Meera Chand7, Peter Werner Schreiber4, Rami Sommerstein8, Christoph Berger9, Michele Genoni10, Christian Rüegg4, Nicolas Troillet11, Andreas F Widmer12, Sören L Becker13, Mathias Herrmann14, Tim Eckmanns15, Sebastian Haller15, Christiane Höller16, Sylvia B Debast17, Maurice J Wolfhagen17, Joost Hopman1, Jan Kluytmans18, Merel Langelaar19, Daan W Notermans20, Jaap Ten Oever21, Peter van den Barselaar22, Alexander B A Vonk23, Margreet C Vos24, Nada Ahmed25, Timothy Brown25, Derrick Crook26, Theresa Lamagni25, Nick Phin25, E Grace Smith27, Maria Zambon25, Annerose Serr28, Tim Götting29, Winfried Ebner29, Alexander Thürmer30, Christian Utpatel2, Cathrin Spröer6, Boyke Bunk6, Ulrich Nübel6, Guido V Bloemberg31, Erik C Böttger5, Stefan Niemann2, Dirk Wagner32, Hugo Sax33. 1. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands. 2. Molecular and Experimental Mycobacteriology, Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany; German Center for Infection Research (DZIF), partner site Borstel, Borstel, Germany. 3. National Mycobacteriology Reference Laboratory, Forschungszentrum Borstel, Borstel, Germany. 4. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. 5. Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; National Center for Mycobacteria, University of Zurich, Zurich, Switzerland. 6. Leibniz-Institute DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Braunschweig, Germany. 7. National Infection Service, Public Health England, London, UK; Guy's and St Thomas' NHS Foundation Trust, London, UK; NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK. 8. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland; Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland. 9. Infectious Diseases and Children's Research, University Children's Hospital Zurich, Zurich, Switzerland. 10. Clinic for Cardiac Surgery, Stadtspital Triemli, Zurich, Switzerland. 11. Service of Infectious Diseases, Central Institute, Valais Hospital, Sion, Switzerland. 12. Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Basel, Basel, Switzerland. 13. Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany; Swiss Tropical and Public Health Institute, Basel, Switzerland. 14. Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany. 15. Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany. 16. Bavarian Health and Food Safety Authority, Oberschleißheim, Germany. 17. Laboratory of Medical Microbiology and Infectious Diseases, Isala, Zwolle, Netherlands. 18. Laboratory for Microbiology and Infection Control, Amphia Hospital, Breda, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. 19. Health Care Inspectorate, Utrecht, Netherlands. 20. National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, Bilthoven, Netherlands. 21. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands. 22. Department of Extracorporeal Circulation, St Antonius Hospital, Nieuwegein, Netherlands. 23. Department of Cardio-Thoracic Surgery, VU University Medical Center, Amsterdam, Netherlands. 24. Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, Netherlands. 25. National Infection Service, Public Health England, London, UK. 26. National Infection Service, Public Health England, London, UK; NIHR Health Protection Research Unit in AMR & HCAI, University of Oxford, Oxford, UK. 27. National Infection Service, Public Health England, London, UK; National Mycobacterial Reference Service, National Infection Service, Public Health Laboratory Birmingham, Birmingham, UK. 28. Center for Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 29. Institute for Infection Prevention and Hospital Epidemiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 30. Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany. 31. Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland. 32. Division of Infectious Diseases, Department of Medicine II, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 33. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. Electronic address: hugo.sax@usz.ch.
Abstract
BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.
BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.
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