Insertion Sequences And Plasmids Are Involved In Increased Carbapenem-Resistant Acinetobacter Baumannii Infections In Two South African Hospitals

Abstract

Background: Acinetobacter baumannii is a serious carbapenem-resistant nosocomial pathogen. Carbapenemase genes such as bla_OXA-23 and bla_NDM and insertion sequences (ISs) near these genes, which can be located on plasmids, primarily contribute to carbapenem resistance in A. baumannii. However, South African studies have not investigated the prevalence of A. baumannii infections and the effect of the carbapenemase genes, ISs, and plasmids on carbapenem resistance. Therefore, this study determined the prevalence of carbapenemase genes, ISs, and plasmids in carbapenem-resistant A. baumannii (CRAB) isolates from patients in two hospitals in the Free State Province, South Africa, and elucidated the effect of ISs and plasmids on carbapenem resistance.

Methods: A total of 1697 CRAB isolates were analysed from patients in the two hospitals from January 2018 to September 2020. Isolates (n = 162/1697) were screened for carbapenemase genes, ISs, and plasmids using the BD MAX Check-Points CPO Assay and a multiplex PCR. Results were compared to the antibiotic susceptibility profiles of the original isolates. Some isolates (n = 30) were Sanger sequenced for gene confirmation and to determine the location of the ISs to the carbapenemase genes and on plasmids.

Results: Most isolates from Universitas (90.5%) and Pelonomi (84.9%) were carbapenem-resistant. The bla_OXA-23 was the most prevalent gene; ISAba1 was present in 144 bla_OXA-23-positive isolates, and ISAba2 was detected in three of these isolates. The bla_NDM was the second most prevalent gene; 42 bla_NDM­-containing isolates had ISAba125. All but one ISAba125-positive isolate was carbapenem-resistant. Nine isolates with only the intrinsic bla_OXA-51-like co-harboured different combinations of the ISs. Most isolates co-harbouring ISAba1 and bla_OXA-23 or only with bla_OXA-51-like were carbapenem-resistant. ISAba2 or ISAba3 did not increase carbapenem resistance. ISAba1 was upstream of bla_OXA-23 in total- and plasmid DNA and upstream of bla_OXA-51-like in total DNA, where they may have assisted in inducing resistance. Forty-two of the plasmid-containing isolates were carbapenem-resistant.

Conclusion: The co-existence of ISs and carbapenemase genes upstream of bla_OXA-51-like, bla_OXA-23, or bla_NDM on plasmids may contribute to carbapenem resistance. Elucidating the effect of ISs on carbapenem resistance can lead to the development of a novel therapeutic agent for CRAB infections.