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Fosfomycin-Overcoming Problematic In Vitro Susceptibility Testing and Tricky Result Interpretation: Comparison of
Jan Závora1,2, Gabriela Kroneislová1, Marie Kroneisl3,4
1Clinical Microbiology and ATB Centre, General University Hospital, 128 08 Prague, Czech Republic.
Antibiotics (Basel, Switzerland)
|November 27, 2024
Summary
Fosfomycin susceptibility testing using disc diffusion and Etest methods showed poor agreement with the reference method, indicating neither is suitable for routine use. Further interpretation criteria are needed for accurate clinical guidance.
Area of Science:
- Clinical microbiology and infectious diseases
- Antimicrobial susceptibility testing (AST)
- Pharmacology and drug resistance
Background:
- Fosfomycin (FOS) is an established antibiotic with renewed interest for treating difficult-to-treat Gram-negative infections.
- Reliable susceptibility testing methods and interpretation criteria are crucial for effective FOS clinical use.
- Current methods require validation against reference standards for routine application.
Purpose of the Study:
- To evaluate the performance of disc diffusion (DD) and Etest® methods for Fosfomycin susceptibility testing.
- To compare these methods against agar dilution (AD) as the reference standard.
- To assess the utility of these methods for Gram-negative bacteria with difficult-to-treat resistance (DTR) and Staphylococcus aureus isolates.
Main Methods:
- A total of 130 bacterial isolates were tested: 40 Enterobacterales (20 DTR, 20 non-DTR), 30 Pseudomonas aeruginosa (15 DTR, 15 non-DTR), and 60 Staphylococcus aureus (30 MSSA, 30 MRSA).
- Disc diffusion (DD) and gradient strip (Etest®) methods were employed.
- Results were interpreted using 2023 European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria and compared to agar dilution (AD).
Main Results:
- Higher FOS resistance rates were observed in DTR Gram-negatives (45% Enterobacterales, 20% P. aeruginosa) compared to non-DTR isolates.
- All Staphylococcus aureus isolates were susceptible to FOS.
- Neither DD nor Etest® showed acceptable agreement with AD for Gram-negative isolates; Etest® performed better for DTR P. aeruginosa (80% CA) than non-DTR (45.7% CA).
- Etest® demonstrated 100% categorical agreement for S. aureus but low essential agreement (47-53%) for MRSA and MSSA.
Conclusions:
- Neither disc diffusion nor Etest® is a suitable alternative to agar dilution for Fosfomycin susceptibility testing in the evaluated bacterial groups.
- The study highlights the need for refined interpretation criteria for Fosfomycin, particularly for Gram-negative pathogens.
- Further research is required to establish robust and reliable susceptibility testing methodologies for Fosfomycin.

