Analysing the determinants of Extended-Spectrum β-Lactamase-producing Escherichia coli and Klebsiella pneumoniae colonisation in the Malawian community setting

Sammarro, Melodie and Jewell, Christopher and Rowlingson, Barry and Feasey, Nicholas (2023) Analysing the determinants of Extended-Spectrum β-Lactamase-producing Escherichia coli and Klebsiella pneumoniae colonisation in the Malawian community setting. PhD thesis, Lancaster University.

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Abstract

Antimicrobial resistance is a health issue of global concern, involving the human, food and environmental sectors. A prime example of this threat is the rapid evolution of Extended-Spectrum β-Lactamase (ESBL)-producing E. coli and K. pneumoniae[1, 2]. These bacterial species are resistant to most β-lactam antibiotics, and in sub-Saharan Africa, where last resort antimicrobials are not always available, they may render ESBL infections untreatable[3]. Interrupting transmission leading to human gut mucosal colonisation appears like an attractive strategy to prevent infections[3]. However, little is known about risk factors for human gut mucosal colonisation with ESBL-producing Enterobacteriaceae (ESBL-E) in community settings in sub-Saharan Africa. Here, we suggest the importance of within-household transmission in driving ESBL colonisation in the community by determining various risk factors for ESBL-producing E. coli and K. pneumoniae. We also highlight faecal-oral and environmental routes as potential routes of transmission, through the identification of gender and various water, sanitation and hygiene (WASH) components as risk factors. These are determined using spatial and longitudinal approaches on the data collected using the modified spatial design described in this thesis. The findings indicate that transmission is complex in this setting, with individual, household and WASH components appearing as important factors. We suggest that main transmission pathways might differ depending on the bacterial species, therefore interventions might need to vary. We also recommend that interventions aimed at preventing transmission might have the best impact when targeted at the household-level and focused on modifying the WASH behavioural practice and/or improving the WASH infrastructure. Additionally, we show that antibiotic use is important when looking at colonisation with ESBL-producing K. pneumoniae and therefore infection prevention and control measures and antibiotic use and stewardship training could help in preventing transmission. Finally, we report a prevalence of ESBL-producing E. coli of 37% in the community setting, which is comparable to some of the highest prevalences reported in the world[4].