Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study


Jinnethe Reyes, Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, Colombia.
Lauren Komarow, The Biostatistics Center, George Washington University, Rockville, MD, USA.
Liang Chen, Center for Discovery and Innovation and Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA.
Lizhao Ge, The Biostatistics Center, George Washington University, Rockville, MD, USA.
Blake M. Hanson, Center for Infectious Diseases and Microbial Genomics, UTHealth, McGovern School of Medicine at Houston, Houston, TX, USA.
Eric Cober, Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, USA.
Erica Herc, Division of Infectious Diseases, Henry Ford Hospital, Detroit, MI, USA.
Thamer Alenazi, College of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Keith S. Kaye, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA; Division of Allergy, Immunology, and Infectious Diseases, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Julia Garcia-Diaz, Division of Infectious Diseases, Ochsner Medical Center, New Orleans, LA, USA.
Lanjuan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China.
Souha S. Kanj, Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon.
Zhengyin Liu, Infectious Disease Section, Department of Internal Medicine, Peking Union Medical College Hospital, Beijing, China.
Jose M. Oñate, Servicio de Medicina Interna, Centro Medico Imbanaco, Cali, Colombia.
Robert A. Salata, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Kalisvar Marimuthu, Department of Infectious Diseases, Tan Tock Seng Hospital, National Centre for Infectious Diseases, Singapore.
Hainv Gao, Department of Infectious Diseases, Shulan Hangzhou Hospital, Hangzhou, China.
Zhiyong Zong, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China.
Sandra L. Valderrama-Beltrán, Infectious Diseases Research Group, School of Medicine, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia.
Yunsong Yu, Department of Infectious Diseases, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Paul Tambyah, National University of Singapore, Infectious Diseases Translational Research Program, Singapore.
Gregory Weston, Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Soraya Salcedo, Servicio de Infectología, Organizacion Clinica General del Norte, Barranquilla, Colombia.
Lillian M. Abbo, Division of Infectious Diseases, University of Miami Hospital, Miami, FL, USA.
Qing Xie, Department of Infectious Disease, Ruijin Hospital, Shanghai, China.
Karen Ordoñez, Department of Infectious Diseases, ESE Hospital Universitario, San Jorge de Pereira, Pereira, Colombia.
Minggui Wang, Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Martin E. Stryjewski, Department of Medicine and Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina.
Jose M. Munita, Millennium Initiative for Collaborative Research on Bacterial Resistance, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicine, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
David L. Paterson, Department of Infectious Diseases, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QL, Australia.
Scott Evans, The Biostatistics Center, George Washington University, Rockville, MD, USA.
Carol Hill, Duke Clinical Research Institute, Duke University, Durham, NC, USA.

Document Type

Journal Article

Publication Date



The Lancet. Microbe




BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.


Biostatistics and Bioinformatics