Transmission dynamics of Klebsiella pneumoniae in a neonatal intensive care unit in Zambia before and after an infection control bundle

Background

Klebsiella pneumoniae is a leading cause of neonatal sepsis in low-and middle-income countries, with antimicrobial resistance (AMR) significantly contributing to associated mortality. Infection prevention and control (IPC) interventions effectively reduced healthcare-associated infections and significantly decreased neonatal mortality in the Sepsis Prevention in Neonates in Zambia (SPINZ) study. Here we use whole genome sequencing to explore the impact of an IPC intervention on K. pneumoniae strains and transmission dynamics responsible for sepsis in a Zambian neonatal unit.

Methods and Findings

Blood culture isolates were collected during the SPINZ study, including a 7-month baseline period and 12 months following implementation of a low-cost IPC bundle. Bacterial isolates were sequenced (using Illumina), assembled, and characterised in terms of lineage, AMR determinants, and polysaccharide antigens (using Kleborate and Kaptive). High-quality genome assemblies were obtained for 411 neonatal K. pneumoniae infections. The K. pneumoniae population was diverse, comprising 24 unique STs, but dominated by ST307 (69.3%, n=285). Nearly all isolates (99.0%) carried extended spectrum beta-lactamases, but few carried carbapenemases (2.7%). Probable transmission clusters were identified using single-linkage clustering with pairwise distance thresholds of ≤4 weeks and ≤10 single nucleotide variants (SNVs) between isolates. Most infections (95.6%) were associated with clusters, ranging in size from 2–202 patients and spanning durations of 2–232 days. Most K. pneumoniae (n=228, 70%) were isolated during the 7-month baseline period and formed six clusters, including one cluster of >200 neonates infected with ST307, which was interrupted by the IPC implementation. Novel clusters emerged during the post-intervention period, including additional STs and distinct ST307 lineages (unrelated to the pre-intervention cluster), but also ST2004 and ST101 clusters that were genetically indistinguishable from those detected pre-intervention.

Conclusions

In this neonatal unit, K. pneumoniae sepsis was mostly attributable to nosocomial transmission clusters, including a large and sustained outbreak of ST307 affecting >200 neonates over eight months. Transmission of all strains was periodically suppressed by an IPC bundle; however not all strains were eliminated, and some were able to re-emerge later to re-establish infection and transmission, alongside newly introduced strains that formed additional transmission clusters.

Some clusters were associated with rapid onset of disease (within 2 days of admission) and others with delayed onset, suggesting different sources of contamination (e.g. reagent vs environmental). These findings reinforce the need for sustained IPC efforts, and better understanding of environmental reservoirs of opportunistic pathogens in neonatal units to inform such efforts.