Acquisition and loss of carriage of antimicrobial resistant Enterobacterales among vulnerable children in Kenya: clinical and genomic determinants

Thesis

Antimicrobial resistance (AMR) is a critical global health challenge, with sub-Saharan Africa experiencing the highest burden of AMR-related mortality. In hospitals, extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) significantly threaten treatment efficacy, particularly in low-resource settings with limited infection control measures. These pathogens are often carried asymptomatically in the gut, with gastrointestinal colonisation serving as a reservoir for transmission and a precursor to invasive disease. However, data on AMR acquisition, risk factors, and dynamics in African children remain scarce.

This thesis examines AMR in hospital-acquired Gram-negative bloodstream infections (HA-GNBSI) in African children, antimicrobial use patterns, and the dynamics of ESBL-E and CRE carriage among Kenyan children across hospital and community settings. Methods include a literature review, antimicrobial prescribing analyses in nine hospitals across Africa and South Asia, and a longitudinal study of Kenyan children from hospital admission to six months post-discharge. The diversity and clonality of invasive versus carriage Escherichia coli strains are also analysed.

Key findings reveal that Klebsiella pneumoniae and Escherichia. coli dominates HA-GNBSI in African children and neonates, with pooled prevalence of HA-GNBSI being 63%. Antimicrobial use patterns show high reliance on WHO Watch antibiotics, while Reserve antibiotics are rarely used. In Kenyan hospitals, ESBL-E carriage increased from 36% at admission to 71% at discharge, dropping to 27% after six months. Commonest ESBL-E genes were CTX-M-15 and sequence type ST38 found in both hospital and community settings, while CRE remained restricted to urban hospitals, dominated by the NDM-5 genotype.

This study highlights the amplification of AMR during hospitalisation and the circulation of resistance genes between hospitals and communities. Findings underscore the need for enhanced antimicrobial stewardship, infection prevention strategies, and evidence-based guidelines which are integrated across hospital and community settings to mitigate AMR in low- and middle-income countries.

Authors: Kipngeno Tigoi, C

• Alternative title: Longitudinal acquisition and loss of carriage of antimicrobial resistance
• DOI: 10.5287/ora-1rwjd4wn0
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: hospitalisation; acquisition; vulnerable children; loss; CRE; ESBL-E; carriage; antimicrobial resistance
• Subjects: Pathogenic microorganisms