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In vitro activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa causing urinary,intra-abdominal and lower respiratory tract infections in intensive care units in Portugal: The STEP multicenter study
Institution:1. Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain;2. Red Española de Investigación en Patología Infecciosa (REIPI), Madrid, Spain;3. Serviço de Microbiologia Centro Hospitalar Lisboa Norte, Lisboa, Portugal;4. Laboratório de Microbiologia, Serviço de Patologia Clínica, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal;5. Laboratório de Microbiologia Clínica Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal;6. Serviço de Microbiologia, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal;7. Serviço Patologia Clínica, Centro Hospitalar Universitário São João, Porto, Portugal;8. Serviço Patologia Clínica, Hospital Infante Dom Pedro, Aveiro, Portugal;9. Serviço de Patologia Clínica, Hospital Prof. Dr. Fernando da Fonseca, Amadora, Portugal;10. Serviço de Microbiologia, Hospital Garcia de Orta, Alnada, Portugal;11. Serviço de Patologia Clínica – Microbiologia – CHUA – Unidade de Portimão, Portimão, Portugal;12. Serviço de Microbiologia do Centro Hospitalar Universitário do Porto, Porto, Portugal;13. Serviço de Microbiologia, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal;14. MSD Portugal, Paço de Arcos, Portugal;1. Aix-Marseille Université, IRD, APHM, MEPHI, IHU Méditerranée Infection, Marseille, France;2. Aix-Marseille Université, IRD, SSA, APHM, VITROME, IHU Méditerranée Infection, Marseille, France;3. Département de cardiologie, Hôpital de la Timone, AP-HM, boulevard Jean-Moulin, 13005 Marseille, France;4. Laboratoire d''hématologie, Hôpital de la Timone, APHM, boulevard Jean Moulin, 13005 Marseille, France;1. Jawaharlal Nehru University, New Delhi 110067, India;2. National Centre for Disease Control, Delhi 110054, India;3. V.M. Govt. Medical College, Solapur, Maharashtra, India;4. SVN Govt. Medical College, Yavatmal, India;5. Defence Research and Development Establishment, Gwalior, India;6. Indian Institute of Science Education and Research (IISER), Berhampur, India;2. Department of Laboratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China;3. Department of Laboratory Medicine, Chongqing Dazu District People''s Hospital, Chongqing, China;4. Department of Clinical Laboratory, University of Chinese Academy of Sciences Chongqing Renji Hospital, Fifth People’s Hospital of Chongqing, Chongqing, China;5. Department of Laboratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China;1. Division of Infection, University College London Hospitals, London, UK;2. Department of Clinical Microbiology, University College London Hospitals, London, UK;3. Department of Infectious Diseases, Cardiff and Vale University Health Board, Cardiff, UK;4. Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK;5. Division of Infection & Immunity, University College London, London, UK;1. Clinical Microbiology Laboratory, Department of Pathology, NorthShore University HealthSystem, Evanston, Illinois;2. Department of Pathology, The University of Chicago Pritzker School of Medicine, Chicago, Illinois;3. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA;4. Sequencing Core, Research Resources Center, University of Illinois at Chicago, Chicago, Illinois;5. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA;6. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA;7. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA
Abstract:The STEP surveillance study was designed to increase knowledge about distribution of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa in Portugal, focusing on the intensive care unit (ICU). Antimicrobial susceptibility of common agents was also evaluated and compared with that of one of the latest therapeutic introductions, ceftolozane-tazobactam (C/T). Clinical isolates of Enterobacterales (n=426) and P. aeruginosa (n=396) from patients admitted in Portuguese ICUs were included. Activity of C/T and comparators was investigated using standard broth microdilution. Isolates were recovered from urinary tract (UTI, 36.9%), intra-abdominal (IAI, 24.2%) and lower respiratory tract (LRTI, 38.9%) infections. In P. aeruginosa, overall distribution of MDR/extremely-drug resistant (XDR)/pan-drug resistant (PDR) isolates accounted for 21.2%, 23.2% and 0.8%, respectively. C/T was the most potent agent tested against P. aeruginosa and MDR/XDR/PDR phenotypes. In Escherichia coli, extended-spectrum beta-lactamases (ESBL) and carbapenemase (CP) phenotypes accounted for 16.6% and 1.7%, respectively, whereas in Klebsiella spp., ESBL and CP-phenotypes represented 28.5% and 17.9%, respectively. Overall, susceptibility of C/T against Enterobacterales was 86.9%. C/T was the least affected agent in E. coli (99.4% susceptibility), whereas its activity was moderate in Klebsiella spp. (71.5%) and Enterobacter spp. (70.4%), due in part to a high rate of ESBL and CP-phenotypes. In Enterobacterales, blaKPC was the most prevalent CP gene (63.0%), followed by blaOXA-48 (33.3%) and blaVIM (3.7%). These microbiological results reinforce C/T as a therapeutic option in ICU patients with UTI, IAI or LRTI due to P. aeruginosa or Enterobacterales isolates, but not for CP producers.
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