Synergistic activity of fosfomycin, β-lactams and peptidoglycan recycling inhibition against Pseudomonas aeruginosa.

摘要: Objectives To evaluate the interconnection between peptidoglycan (PG) recycling, fosfomycin susceptibility and synergy β-lactams in Pseudomonas aeruginosa METHODS: Fosfomycin MICs were determined by broth microdilution Etest for a panel of 47 PAO1 mutants defective several components PG recycling and/or AmpC induction pathways. also presence 5 mM concentration NagZ inhibitor PUGNAc. Population analysis characterization resistant that emerged was performed selected strains. Finally, fosfomycin, imipenem + killing curves assessed. Results Mutants AmpG, or all three AmpD amidases showed marked increase (at least two 2-fold dilutions with respect to WT PAO1). Moreover, consistently reduced from 48 24 mg/L hypersusceptibility ampG, nagZ triple ampD clearly confirmed population analysis, although emergence mutants, through GlpT mutations, not avoided. Synergy evidenced strain, AmpC-hyperproducing strain (triple mutant) AmpG curves. regrowth combination. Conclusions inhibitors are envisaged as useful adjuvants treatment P. infections therefore further development these molecules is encouraged.