BETA-LACTAM-FOSFOMYCIN ANTAGONISM INVOLVING MODIFICATION OF PENICILLIN-BINDING PROTEIN 3 IN PSEUDOMONAS-AERUGINOSA

Antagonism between fosfomycin and antipseudomonal penicillins, cefotaxime, and ceftriaxone was observed in Pseudomonas aeruginosa RYC212. Fosfomycin, a non-β-lactam antibiotic that acts on bacterial cell wall synthesis, decreased the expression of penicillin-binding protein 3 and induced β-lactamase. The antagonistic effect was reduced in the presence of high concentrations of the β-lactamase inhibitor tazobactam or in fosfomycin-resistant mutants. We suggest that products resulting from fosfomycin cell wall damage could interact with a system that regulates penicillin-binding protein and β-lactamase production.