Investigation of in vitro susceptibility of OXA48 carbapenemase-producing Enterobacterales to ceftazidime-avibactam over a 4-year period : a longitudinal retrospective study

Abstract

ackground One of the many health issues plaguing our society is the emergence of infectious agents that are resistant to treatment. This has resulted in multiple deaths over the years. Among multi-drug resistant pathogens of note are carbapenemase-producing Enterobacterales (CPE). As one of the measures to treat these super-bugs, the ceftazidime-avibactam (CZA) drug was formulated, and approved by the Food and Drug Administration (FDA) in 2015. Though not yet registered in South Africa at that time, susceptibility testing for CZA commenced at Lancet Laboratories in 2020. The drug was registered in South Africa in 2021. In the never-ending struggle to prevent the development of resistance to new drugs, surveillance measures need to be put in place to facilitate early detection of the beginning of a resistance pattern. In this way, early action can be taken to prevent further development of resistance. Material and Methods In this study, susceptibility patterns of the OXA48 subtype of CPE were measured and compared over 24 months to detect any resistance trend. In addition, isolates stored prior to 2020 were tested for CZA susceptibility, and a comparison made to the post-CZA-testing group. The demographic distribution of the OXA48 infections was also analysed. The different species of OXA48 CPE were compared to determine which of the enterobacterales exhibits more resistance to CZA. The PCR method was used to determine the carbapenemase type. The K-B method was used to determine CZA susceptibility. Bacterial identification was obtained using the MALDI-MS method. Results All eight OXA48 isolates from 2018 and 2019 were susceptible to CZA, yielding 0% resistance. 6% of the OXA48 isolates from 2020 were resistant, while 9% from 2021 were resistant. 81% of all the OXA48 isolates from 2020/2021 were Klebsiella pneumoniae, while the same species constituted 86% of the CZA resistant population. 58% of the OXA48 isolates from 2020/2021 were isolated from the Durban area. There was 100% CZA susceptibility in the 2018/2019 period, compared to the 92.5% in the 2020/2021 period. Conclusion The beginning of a resistance trend was observed between the years 2020 and 2021. Klebsiella pneumoniae was the predominant species of OXA48 CPE isolated. Most OXA48 isolates cultured between January 2020 and December 2021 were from the Durban area. No statistical significance was discovered in the difference in CZA susceptibility between the 2018/2019 and the 2020/2021 periods.