Uduak Okomo1, Madikay Senghore2, Saffiatou Darboe3, Ebrima Bojang4, Syed M A Zaman5, Mohammad Jahangir Hossain6, Davis Nwakanma6, Kirsty Le Doare7, Kathryn E Holt8, Nina Judith Hos9, Joy E Lawn10, Stephen D Bentley11, Beate Kampmann12. 1. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia. Electronic address: uokomo@mrc.gm. 2. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia; Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA. 3. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia. 4. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK. 5. Liverpool School of Tropical Medicine, Liverpool, UK. 6. Disease Control and Elimination Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia. 7. Institute of Infection and Immunity, St George's University of London, Cranmer Terrace, London, UK. 8. The Vaccine Centre, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia. 9. The Vaccine Centre, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. 10. Maternal, Adolescent, Reproductive, & Child Health Centre, London School of Hygiene & Tropical Medicine, London, UK. 11. Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Department of Pathology, University of Cambridge, Cambridge, UK; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK. 12. Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia; The Vaccine Centre, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Abstract
BACKGROUND: Sick newborns admitted to neonatal units in low-resource settings are at an increased risk of developing hospital-acquired infections due to poor clinical care practices. Clusters of infection, due to the same species, with a consistent antibiotic resistance profile, and in the same ward over a short period of time might be indicative of an outbreak. We used whole-genome sequencing (WGS) to define the transmission pathways and characterise two distinct outbreaks of neonatal bacteraemia in a west African neonatal unit. METHODS: We studied two outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in a neonatal unit that provides non-intensive care on the neonatal ward in the Edward Francis Small Teaching Hospital, Banjul, The Gambia. We used WGS to validate and expand findings from the outbreak investigation. We retrospectively sequenced all clinical isolates associated with each outbreak, including isolates obtained from swabs of ward surfaces, environmental fluid cultures, intravenous fluids, and antibiotics administered to newborns. We also sequenced historical B cepacia isolates associated with neonatal sepsis in the same ward. RESULTS: Between March 1 and Dec 31, 2016, 321 blood cultures were done, of which 178 (55%) were positive with a clinically significant isolate. 49 episodes of neonatal B cepacia bacteraemia and 45 episodes of bacteraemia due to ESBL-producing K pneumoniae were reported. WGS revealed the suspected K pneumoniae outbreak to be contemporaneous outbreaks of K pneumoniae (ST39) and previously unreported Klebsiella quasipneumoniae subspecies similipneumoniae (ST1535). Genomic analysis showed near-identical strain clusters for each of the three outbreak pathogens, consistent with transmission within the neonatal ward from extrinsically contaminated in-use intravenous fluids and antibiotics. Time-dated phylogeny, including retrospective analysis of archived bacterial strains, suggest B cepacia has been endemic in the neonatal ward over several years, with the Klebsiella species a more recent introduction. INTERPRETATION: Our study highlights the emerging threat of previously unreported strains of multidrug-resistant Klebsiella species in this neonatal unit. Genome-based surveillance studies can improve identification of circulating pathogen strains, characterisation of antimicrobial resistance, and help understand probable infection acquisition routes during outbreaks in newborn units in low-resource settings. Our data provide evidence for the need to regularly monitor endemic transmission of bacteria within the hospital setting, identify the introduction of resistant strains from the community, and improve clinical practices to reduce or prevent the spread of infection and resistance. FUNDING: Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
BACKGROUND: Sick newborns admitted to neonatal units in low-resource settings are at an increased risk of developing hospital-acquired infections due to poor clinical care practices. Clusters of infection, due to the same species, with a consistent antibiotic resistance profile, and in the same ward over a short period of time might be indicative of an outbreak. We used whole-genome sequencing (WGS) to define the transmission pathways and characterise two distinct outbreaks of neonatal bacteraemia in a west African neonatal unit. METHODS: We studied two outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in a neonatal unit that provides non-intensive care on the neonatal ward in the Edward Francis Small Teaching Hospital, Banjul, The Gambia. We used WGS to validate and expand findings from the outbreak investigation. We retrospectively sequenced all clinical isolates associated with each outbreak, including isolates obtained from swabs of ward surfaces, environmental fluid cultures, intravenous fluids, and antibiotics administered to newborns. We also sequenced historical B cepacia isolates associated with neonatal sepsis in the same ward. RESULTS: Between March 1 and Dec 31, 2016, 321 blood cultures were done, of which 178 (55%) were positive with a clinically significant isolate. 49 episodes of neonatal B cepacia bacteraemia and 45 episodes of bacteraemia due to ESBL-producing K pneumoniae were reported. WGS revealed the suspected K pneumoniae outbreak to be contemporaneous outbreaks of K pneumoniae (ST39) and previously unreported Klebsiella quasipneumoniae subspecies similipneumoniae (ST1535). Genomic analysis showed near-identical strain clusters for each of the three outbreak pathogens, consistent with transmission within the neonatal ward from extrinsically contaminated in-use intravenous fluids and antibiotics. Time-dated phylogeny, including retrospective analysis of archived bacterial strains, suggest B cepacia has been endemic in the neonatal ward over several years, with the Klebsiella species a more recent introduction. INTERPRETATION: Our study highlights the emerging threat of previously unreported strains of multidrug-resistant Klebsiella species in this neonatal unit. Genome-based surveillance studies can improve identification of circulating pathogen strains, characterisation of antimicrobial resistance, and help understand probable infection acquisition routes during outbreaks in newborn units in low-resource settings. Our data provide evidence for the need to regularly monitor endemic transmission of bacteria within the hospital setting, identify the introduction of resistant strains from the community, and improve clinical practices to reduce or prevent the spread of infection and resistance. FUNDING: Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.
Authors: Bakary Sanyang; Thushan I de Silva; Abdoulie Kanteh; Abdoulie Bojang; Jarra Manneh; Wouter A A de Steenhuijsen Piters; Chikondi Peno; Debby Bogaert; Abdul Karim Sesay; Anna Roca Journal: EBioMedicine Date: 2022-08-19 Impact factor: 11.205