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In vitro assessment of the synergistic effects of cefotaxime, colistin, and fosfomycin combinations against foodborne resistant Escherichia coli and Salmonella isolates

The Journal of Antibiotics volume 78, pages 265–273 (2025)Cite this article

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Abstract

The emergence of multidrug-resistant pathogens, particularly β-lactam, colistin, and fosfomycin-resistant Escherichia coli and Salmonella, is a significant public health concern. This study evaluated the in vitro synergistic effects of antimicrobial combinations against these resistant isolates. Ten isolates that originated from retail chicken meat, including five E. coli and five Salmonella isolates, were tested against cefotaxime (CTA), fosfomycin (FOS), and colistin (COL), both individually and in combinations. Antimicrobial susceptibility was assessed using the broth microdilution method, and synergistic interactions were evaluated using checkerboard and time-killing assays. All isolates were multidrug-resistant (MDR) and were resistant to CTA, COL, and FOS. The checkerboard assay showed varying levels of synergy: two out of five E. coli isolates exhibited synergy with FOS-COL, while one E. coli isolates out of four isolates showed synergy with CTA-COL. No E. coli isolates showed synergy with FOS-CTA. For Salmonella, two out of five isolates exhibited synergy with both FOS-CTA and FOS-COL, while three out of four isolates showed synergy with CTA-COL. The time-killing assay confirmed these results, with the FOS-COL combinations showing synergy against both E. coli and Salmonella strains. Notably, the FOS-COL combination demonstrated bactericidal effects against E. coli, and all three combinations were bactericidal against Salmonella. The study highlights the potential of antimicrobial combinations, particularly FOS-COL, in combating MDR E. coli and Salmonella. These findings support the use of combination therapy as a promising strategy to in effectively treating multi-drug-resistant foodborne infections, ensuring better medical outcomes and enhanced food safety, warranting further investigation into their mechanisms and clinical applications.

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Funding

This research was supported by the United Arab Emirates University (UAEU) Start-up (proposal number 3219) and Sure Plus (proposal number 2837) grants for H.O.K. M.-Y.I.M is a post-doc fellow funded by ASPIRE, the technology program management pillar of Abu Dhabi’s Advanced Technology Research Council (ATRC), via the ASPIRE Research Institute for Food Security in the Drylands (ARIFSID) project (Subtheme 4.1—One Health and Antimicrobial Resistance).

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Authors and Affiliations

  1. Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain P.O. Box 1555, Al Ain, UAE

    Hazim O. Khalifa, Temesgen Mohammed, Mohamed-Yousif Ibrahim Mohamed & Ihab Habib

  2. Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, 3351, Egypt

    Hazim O. Khalifa

  3. ASPIRE Research Institute for Food Security in the Drylands (ARIFSID), United Arab Emirates University, Al Ain P.O. Box 15551, Al Ain, UAE

    Mohamed-Yousif Ibrahim Mohamed & Ihab Habib

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, 82524, Egypt

    Hamada Hashem

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  1. Hazim O. Khalifa
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Correspondence to Hazim O. Khalifa.

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Khalifa, H.O., Mohammed, T., Mohamed, MY.I. et al. In vitro assessment of the synergistic effects of cefotaxime, colistin, and fosfomycin combinations against foodborne resistant Escherichia coli and Salmonella isolates. J Antibiot 78, 265–273 (2025). https://doi.org/10.1038/s41429-025-00808-9

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