Genomic analysis of sequential outbreaks of Burkholderia cepacia and multi-drug resistant extended spectrum beta-lactamase producing Klebsiella species in a West African tertiary hospital neonatal unit. GAMBIAN NEONATAL OUTBREAK

Background Sick newborns admitted to neonatal units in low resource settings are at an increased risk for 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 may be indicative of an outbreak. We used whole-genome sequencing to define the transmission pathways and characterize two distinct outbreaks of neonatal bacteraemia in a West African neonatal unit Methods We studied two outbreaks of Burkholderia cepacia and multi-drug resistant extended spectrum β-lactamase (ESBL)-producing K. pneumoniae on a non-intensive care neonatal unit in The Gambia. We used whole-genome sequencing 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 Forty-nine episodes of neonatal B. cepacia bacteraemia and 45 episodes of bacteraemia due to ESBL-producing K. pneumoniae were reported in a 10-month period in 2016. Whole-genome sequencing revealed the suspected K. pneumoniae outbreak to be contemporaneous outbreaks of K. pneumoniae (ST39) and previously unreported K. quasipneumoniae subsp 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 that B. cepacia has been endemic in the neonatal ward over several years, with the Klebsiella species only more recently introduced into the hospital environment. Conclusions 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 low-resource setting newborn units. Our data provide evidence for the need to regularly monitor endemic transmission of bacteria within the hospital setting, the introduction of resistant strains from the community, and improve clinical practices to reduce or prevent the spread of infection and resistance.