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Faculty of Health Sciences

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    Investigation of in vitro susceptibility of OXA48 carbapenemase-producing Enterobacterales to ceftazidime-avibactam over a 4-year period : a longitudinal retrospective study
    (2023-05) Ndumo, Nomagugu; Mbatha, Joyce Nonhlanhla
    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.
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    Invitro antibacterial activity of imidazole and triazole-based antimicrobials against Carbapenem Resistant Enterobacteriaceae
    (2019-09-05) Radebe, Siyabonga Protus; Ndlovu, Thandie Sylph
    Introduction The frequency of serious bacterial infections has increased due to the high prevalence of HIV infection, contributing to the increasing rates of multi-drug organisms which include carbapenem-resistant Enterobacteriaceae (CRE). This trend has become a serious challenge to the health care system of South Africa, resulting in the higher use of immunosuppressive and cytotoxic drugs to treat serious bacterial infections. Optimal treatment for infections caused by CRE is yet unknown. The benefits of imidazole and triazole antimicrobials have become very topical due their diverse spectrum of pharmacological properties, but its efficacy against bacterial infections has not been tested in the South African context. Aim The primary aim of this study was to determine the antibacterial effects of selected imidazole and triazole-based antimicrobials against Carbapenem-Resistant Enterobacteriaceae. Methodology Different concentrations of test drugs (ketoconazole, metronidazole and fluconazole) were used to prepare sensitivity disks and four pathogenic strains of Carbapenem Resistant Enterobacteriaceae (K. pneumonia, E. coli, S. marcescens and C. freundii) obtained from Lancet Laboratory in Durban were used to determine the antibacterial activity of the selected test drugs, using Disk Diffusion, Modified Agar Diffusion and Minimum Inhibition Concentration (MIC) method, described by Bauer et al. 1966. Results Antimicrobial Susceptibility Testing revealed that, test drugs selected for this study have no inhibition activity against CRE test organisms and biochemical tests also showed that imidazole and triazoles antimicrobials have no adverse effects on the CRE organisms. Conclusion Although the results obtained in this study indicated no activity of against CRE, laboratory studies are still necessary in modification of the imidazole and triazoles to synthesize derived drugs to confirm and optimize the antibacterial potency of these compounds.