Original Research

Fosfomycin susceptibility testing and resistance mechanisms in Enterobacterales in South Africa

Jessica S. Hurwitz, Mae Newton-Foot, Kristien Nel van Zyl, Pieter Nel
African Journal of Laboratory Medicine | Vol 13, No 1 | a2252 | DOI: https://doi.org/10.4102/ajlm.v13i1.2252 | © 2024 Jessica Sarah Hurwitz, Mae Newton-Foot, Kristien Nel van Zyl, Pieter Nel | This work is licensed under CC Attribution 4.0
Submitted: 05 July 2023 | Published: 19 March 2024

About the author(s)

Jessica S. Hurwitz, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Mae Newton-Foot, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and Department of Medical Microbiology, Tygerberg Hospital, National Health Laboratory Service, Cape Town, South Africa
Kristien Nel van Zyl, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Pieter Nel, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and Department of Medical Microbiology, Tygerberg Hospital, National Health Laboratory Service, Cape Town, South Africa

Abstract

Background: Fosfomycin treatment of urinary tract infections is increasingly attractive due to escalating antibiotic resistance rates among urinary pathogens. Standard antibiotic susceptibility testing methods perform poorly for fosfomycin as there is poor correlation between susceptibility results and clinical outcomes in urinary pathogens other than Escherichia coli.

Objective: We evaluated the performance of fosfomycin susceptibility testing in E. coli and Klebsiella pneumoniae to determine whether fosfomycin susceptibility is associated with molecular resistance mechanisms.

Methods: Forty-six each of E. coli and K. pneumoniae clinical isolates were obtained from a tertiary hospital in South Africa, from 01 June 2017 to 31 January 2018. Agar dilution, disk diffusion, and gradient diffusion were performed and interpreted using the Clinical Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines. Molecular resistance mechanisms were identified by whole genome sequence analysis.

Results: Disk diffusion and gradient diffusion were accurate alternatives for fosfomycin susceptibility testing in E. coli (98% categorical agreement), but not in K. pneumoniae (47% categorical agreement). All E. coli isolates contained at least one resistance mechanism, but only one isolate with a fosA gene was resistant. In K. pneumoniae, 63% (29/46) and 70% (32/46) of isolates were susceptible to fosfomycin, using Clinical Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively, despite all isolates containing a fosA gene and a uhpT mutation.

Conclusion: A better understanding of fosfomycin susceptibility and improved antibiotic susceptibility testing tools could improve diagnostic capability and clinical guidelines for fosfomycin treatment of urinary tract infections.

What this study adds: This study highlights the importance of adhering to interpretive guidelines when performing antimicrobial susceptibility testing and the need for simplified, accurate and standardised susceptibility testing methodology and interpretation for fosfomycin in Enterobacterales organisms.


Keywords

fosfomycin; phenotypic susceptibility testing; molecular resistance mechanisms; Escherichia coli; Klebsiella pneumoniae; Enterobacterales

Sustainable Development Goal

Goal 3: Good health and well-being

Metrics

Total abstract views: 1445
Total article views: 720


Crossref Citations

No related citations found.