The Effect of Multi-drug Resistance on the Fitness and Pathogenicity of Carbapenem Resistant Organisms (CROs) in the Absence of Selective Pressure

Amulele, Anne Vuruku (2022). The Effect of Multi-drug Resistance on the Fitness and Pathogenicity of Carbapenem Resistant Organisms (CROs) in the Absence of Selective Pressure. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00014f99

Abstract

Antimicrobial resistance (AMR) is a global threat estimated to cause millions of deaths and trillions of dollars in economic loss if not dealt with urgently. Carbapenems are one of the last resort drugs used to treat patients with multi-drug resistant infections. In Kenya, carbapenems are minimally used in public hospitals due to cost and availability but are readily available in private healthcare facilities. At Kilifi County Hospital, carbapenems were introduced for patient care in 2020 but resistant bacteria have been isolated prior to this.

In this thesis, I describe the phenotypic and genomic characteristics of carbapenem resistant Acinetobacter spp, P. aeruginosa, E. coli and K. pneumoniae isolated from patients in Kenya, and the effect of resistance on the fitness and virulence of these bacteria. First, I determined that majority of the infections likely occurred in hospital and resistant bacteria are also carried in the gut of some of the admitted patients. Secondly, the strains were resistant not only to commonly known drugs but to newer drugs such as cefiderocol and eravacycline, which are currently not available in the country. Third, my findings showed that metallo-beta-lactamases are the main carbapenemases present in the resistant strains with blaNDM variants being the most common enzyme detected. Fourth, whole genome sequencing showed that the strains harboured various resistant genes and mutations and were of different sequence types suggesting multiple introductory events of the bacteria into hospital. Finally, I demonstrated that while overall carbapenem resistant bacteria were less fit compared to fully susceptible bacteria, this was not always the case for all strains.

In conclusion, diverse strains of carbapenem resistant bacteria causing clinical infections are present and could easily be disseminated countrywide given their carriage in the gut and increasing use of antibiotics such as cephalosporins. Therefore, several measures such as antimicrobial stewardship, infection prevention control, increased access to clean water and improved sanitation are also needed in this country to prevent an increased prevalence of these bacteria.

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