1, 2 The rapid emergence and spread of multidrug-resistant pathogens including Pseudomonas aeruginosa has resulted in revived interest in the parenteral use of fosfomycin to treat infections other than UTIs.
Oral fosfomycin has been approved by the Food and Drug Administration for the treatment of uncomplicated urinary tract infections (UTIs) in adult women that is caused by Escherichia coli. Before it can be used as a framework for the design of antimicrobial therapy, the existence of the window must be demonstrated not only in vitro but also in vivo.įosfomycin is a natural antibacterial agent that has been known for >40 years. MSW theory may not apply to all antimicrobial-pathogen combinations. The emergence of antibiotic resistance is shaped by several factors. coli showed a decreased growth rate compared with the susceptible parental strains, whereas no fitness cost in P. Interestingly, the in vitro-isolated resistant mutants of E. coli was not observed in vivo, regardless of fosfomycin dosage.
In contrast, the emergence of resistant mutants of E. aeruginosa at fosfomycin concentrations fluctuated between the lower and upper boundaries of the MSW. In our animal model, the loss in susceptibility of P. With the in vitro time-kill studies, there were bacterial re-growth and emergence of resistance thereafter for both strains at antibiotic concentrations of × 4, × 8 and × 16 MIC. aeruginosa ATCC 27853, were exposed to fosfomycin at concentrations below MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC in Luria-Bertani broth and in a tissue-cage infection model, respectively. Two standard strains of Gram-negative bacteria, those are E. The purpose of this study was to validate the mutant selection window (MSW) hypothesis in vitro and in vivo with Escherichia coli and Pseudomonas aeruginosa exposed to fosfomycin.
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