Characterization of colistin-resistant Acinetobacter baumannii and Klebsiella pneumoniae isolates from a tertiary-level hospital in Johannesburg, South Africa

Abstract

Colistin is a last-line antibiotic for multidrug-resistant (MDR) gram-negative infections and has become less effective due to the emergence of colistin resistance. In South Africa, colistin resistance in Acinetobacter baumannii and Klebsiella pneumoniae have been reported, but the data is limited. This study characterised colistin-resistant A. baumannii and K. pneumoniae isolates from a tertiary-level hospital in Johannesburg from January 2022 to June 2024 through epidemiological and molecular analysis. From 2900 A. baumannii and K. pneumoniae isolates, 830 underwent colistin broth microdilution (BMD) testing, with 22% (186/830) confirmed as colistin-resistant and 62% (116/186) were extensively drug-resistant (XDR). Klebsiella pneumoniae accounted for 63% (117/186) of all infections. Most colistin-resistant infections were from the adult intensive care units (ICUs) (45%, 84/186). Whole-genome sequencing of 60 isolates revealed no mobile colistin resistance (mcr) genes but identified chromosomal mutations linked to colistin resistance, including pmrA M12I in A. baumannii sequence type (ST)231 and pmrB R256G in five K. pneumoniae ST2497, with one also carrying phoQ G385S and an unidentified K. pneumoniae ST harbouring pmrB R256G mutation. Novel chromosomal mutations were also discovered, with four A. baumannii isolates harbouring a novel non-synonymous pmrC I131V mutation. This study provides new molecular and epidemiological insights into colistin resistance in a South African healthcare setting. The findings highlight the predominance of chromosomal- mediated colistin resistance mechanisms and the identification of novel variants. These insights advance our understanding of resistance evolution and emphasise the need for strengthened genomic surveillance.