Andrew J Stewardson1, Kalisvar Marimuthu2, Sharmila Sengupta3, Arthur Allignol4, Maisra El-Bouseary5, Maria J Carvalho6, Brekhna Hassan6, Monica A Delgado-Ramirez7, Anita Arora8, Ruchika Bagga9, Alex K Owusu-Ofori10, Joseph O Ovosi11, Shamsudin Aliyu12, Hala Saad13, Souha S Kanj13, Basudha Khanal14, Balkrishna Bhattarai15, Samir K Saha16, Jamal Uddin17, Purabi Barman18, Latika Sharma19, Tarek El-Banna20, Rabaab Zahra21, Mansab Ali Saleemi21, Amarjeet Kaur22, Kenneth Iregbu23, Nkolika Sc Uwaezuoke23, Pierre Abi Hanna24, Rita Feghali25, Ana L Correa26, Maria I Munera27, Thi Anh Thu Le28, Thi Thanh Nga Tran29, Chimanjita Phukan30, Chiranjita Phukan31, Sandra L Valderrama-Beltrán32, Carlos Alvarez-Moreno33, Timothy R Walsh6, Stephan Harbarth34. 1. Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, WHO Collaborating Center, Geneva, Switzerland; Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia; Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA. Electronic address: andrew.stew@rdson.net. 2. Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, WHO Collaborating Center, Geneva, Switzerland; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; National Centre for Infectious Diseases, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3. Clinical Microbiology and Infection Control, Medanta, The Medicity Hospital, Delhi NCR, India. 4. Institute of Statistics, Ulm University, Ulm, Germany. 5. Pharmaceutical Microbiology, Tanta University, Tanta, Egypt; Institute of Infection and Immunity, School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UK. 6. Institute of Infection and Immunity, School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UK. 7. "Dr Manuel Gea Gonzalez" General Hospital, Mexico City, Mexico. 8. Fortis Healthcare Limited, Gurgaon, India. 9. Microbiology, Fortis Memorial Research Institute, Gurgaon, India. 10. Clinical Microbiology, Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 11. Internal Medicine, Clinical Pharmacology and Therapeutics, Kaduna State University, Barau Dikko Teaching Hospital, Kaduna, Nigeria. 12. Medical Microbiology, Ahmadu Bello University, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. 13. Internal Medicine, Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon. 14. Microbiology and Infectious Diseases, Bishweshwar Prasad Koirala Institute of Health Sciences, Dharan, Nepal. 15. Anaesthesiology and Critical Care, Bishweshwar Prasad Koirala Institute of Health Sciences, Dharan, Nepal. 16. Department of Microbiology, Dhaka Shishu Hospital, Dhaka, Bangladesh. 17. Department of Microbiology, Child Health Research Foundation, Dhaka, Bangladesh. 18. Clinical Microbiology and Hospital Infection Control, BLK Super Specialty Hospital, New Delhi, India. 19. Clinical Microbiology, BLK Super Specialty Hospital, New Delhi, India. 20. Pharmaceutical Microbiology, Tanta University, Tanta, Egypt. 21. Department of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan. 22. Clinical Microbiology, Medanta, The Medicity Hospital, Delhi NCR, India. 23. Department of Medical Microbiology and Parasitology, National Hospital, Abuja, Nigeria. 24. Department of Medicine, Rafik Hariri University Hospital, Beirut, Lebanon. 25. Department of Laboratory Medicine, Rafik Hariri University Hospital, Beirut, Lebanon. 26. Infectious diseases, Hospital Pablo Tobón Uribe, Medellín, Colombia. 27. Medical Microbiology, Hospital Pablo Tobón Uribe, Medellín, Colombia. 28. Infection Control, Cho Ray Hospital, Ho Chi Minh City, Vietnam. 29. Microbiology, Cho Ray Hospital, Ho Chi Minh City, Vietnam. 30. Department of Microbiology, Gauhati Medical College and Hospital, Guwahati, India. 31. Department of Medicine, Gauhati Medical College and Hospital, Guwahati, India. 32. Infectious Diseases, Internal Medicine, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia. 33. Infectious Diseases, Internal Medicine Department, Universidad Nacional de Colombia, Bogotá, Colombia. 34. Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, WHO Collaborating Center, Geneva, Switzerland.
Abstract
BACKGROUND: Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. METHODS: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. FINDINGS: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15-61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3-6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04-2·94), and decreased probability of discharge alive (0·61, 0·45-0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. INTERPRETATION: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. FUNDING: bioMérieux.
BACKGROUND: Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. METHODS: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. FINDINGS: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15-61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3-6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04-2·94), and decreased probability of discharge alive (0·61, 0·45-0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. INTERPRETATION:Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. FUNDING: bioMérieux.
Authors: Max W Adelman; Chris W Bower; Julian E Grass; Uzma A Ansari; Elizabeth A Soda; Isaac See; Joseph D Lutgring; Jesse T Jacob Journal: Open Forum Infect Dis Date: 2021-12-29 Impact factor: 3.835
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Authors: Gamal Wareth; Jörg Linde; Ngoc H Nguyen; Tuan N M Nguyen; Lisa D Sprague; Mathias W Pletz; Heinrich Neubauer Journal: Antibiotics (Basel) Date: 2021-05-11
Authors: A Olowo-Okere; Y K E Ibrahim; B O Olayinka; J O Ehinmidu; Y Mohammed; L Z Nabti; J-M Rolain; S M Diene Journal: New Microbes New Infect Date: 2020-08-01