New perspectives for reassessing fosfomycin: applicability in current clinical practice

Area of Science:

• Pharmacology and Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Fosfomycin, a bactericidal antibiotic, inhibits bacterial cell wall synthesis with broad-spectrum activity.
• Regulatory agencies like EMA and FDA are reviewing fosfomycin data for updated usage guidelines and US market approval.
• Understanding fosfomycin's microbiological profile and clinical applications is crucial for combating resistant bacterial infections.

Purpose of the Study:

• To review current aspects of fosfomycin, including its mechanism of action, synergistic potential, and resistance mechanisms.
• To analyze discrepancies in susceptibility testing cutoffs and their impact on dosing recommendations.
• To evaluate fosfomycin's efficacy in treating various infections, particularly those caused by multidrug-resistant organisms.

Main Methods:

• Review of microbiological data on fosfomycin's mechanism of action and synergistic effects with other antibiotics.
• Analysis of reported bacterial resistance mechanisms to fosfomycin.
• Examination of clinical data regarding fosfomycin's efficacy, pharmacokinetics, pharmacodynamics, and dosing in different patient populations and infection types.

Main Results:

• Fosfomycin exhibits a single mechanism of action, offering synergistic potential with various antibiotic classes.
• Resistance mechanisms involve reduced transport, target modification, and direct inactivation; clinical impact varies.
• Discrepancies in susceptibility breakpoints (CLSI vs. EUCAST) and varying MICs necessitate specific dosing regimens for multidrug-resistant infections.

Conclusions:

• Fosfomycin demonstrates broad-spectrum activity and synergistic potential, making it valuable against multidrug-resistant Gram-negative and Gram-positive bacteria.
• Optimal dosing strategies are essential, considering pathogen type, patient profile, and infection model, with specific high-dose regimens recommended for resistant infections.
• Fosfomycin is a key treatment for cystitis, especially for ESBL-producing bacteria, and shows promise in treating complex infections like osteoarticular infections and those caused by extensively resistant Gram-negatives.