Investigation of sequential outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase producing Klebsiella species in a West African tertiary hospital neonatal unit: a retrospective genomic analysis

Uduak Okomo*, Madikay Senghore, Saffiatou Darboe, Ebrima Bojang, Syed M.A. Zaman, Mohammad Jahangir Hossain, Davis Nwakanma, Kirsty Le Doare, Kathryn E. Holt, Nina Judith Hos, Joy E. Lawn, Stephen D. Bentley, Beate Kampmann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e119-e129
JournalThe Lancet Microbe
Volume1
Issue number3
DOIs
Publication statusPublished - Jul 2020
Externally publishedYes

Bibliographical note

Funding Information:
BK reports grants from maternal and neonatal health research, including vaccine studies, outside the submitted work. KLD reports grants from UK Research and Innovation and European and Developing Countries Clinical Trials Partnership, outside the submitted work. All other authors declare no competing interests.

Funding Information:
This work is supported by the Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine (LSHTM). Work at the MRC Unit is jointly funded by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. UO was supported by an MRC PhD Fellowship. BK is supported by funding from the MRC (MC_UP_A900/1122; MC_UP_A900/115; MR/K007602/1) and acknowledges the contribution of a Thrasher Senior Investigator award to this work. NJH was supported by a Research Fellowship by the German Research Foundation (HO 6280/1?1). We thank Muhammed Afolabi for providing technical support at the Edward Francis Small Teaching Hospital; Baderinwa Abatan, Helen Brotherton, and Abdou Gai for assistance with clinical data collection; Ousman Secka and Bolarinde Lawal for oversight of environmental sampling; Buntung Ceesay and Mamadou Jallow for microbiological support; and Jonas Lexow for providing technical support at the MRC Unit The Gambia at LSHTM.

Funding Information:
This work is supported by the Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene & Tropical Medicine (LSHTM). Work at the MRC Unit is jointly funded by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. UO was supported by an MRC PhD Fellowship. BK is supported by funding from the MRC (MC_UP_A900/1122; MC_UP_A900/115; MR/K007602/1) and acknowledges the contribution of a Thrasher Senior Investigator award to this work. NJH was supported by a Research Fellowship by the German Research Foundation (HO 6280/1–1). We thank Muhammed Afolabi for providing technical support at the Edward Francis Small Teaching Hospital; Baderinwa Abatan, Helen Brotherton, and Abdou Gai for assistance with clinical data collection; Ousman Secka and Bolarinde Lawal for oversight of environmental sampling; Buntung Ceesay and Mamadou Jallow for microbiological support; and Jonas Lexow for providing technical support at the MRC Unit The Gambia at LSHTM.

Publisher Copyright:
© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

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