fosfomycin
Mechanisms of ResistanceCharacterization of FosL1, a Plasmid-Encoded Fosfomycin Resistance Protein Identified in Escherichia coliFosfomycin is gaining renewed interest for treating urinary tract infections. Monitoring fosfomycin resistance is therefore important in order to detect the emergence of novel resistance mechanisms. Here, we used the Rapid Fosfomycin NP test to screen a collection of extended-spectrum-β-lactamase-producing Escherichia coli isolates from Switzerland and found a...
Clinical TherapeuticsOral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against Enterobacterales: the Importance of Heteroresistance for Growth OutcomeOral fosfomycin trometamol is licensed as a single oral dose for the treatment of uncomplicated urinary tract infections, with activity against multidrug-resistant uropathogens. The impact of interindividual variability in urinary concentrations on antimicrobial efficacy, and any benefit of giving multiple doses, is uncertain.
PharmacologyEx Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult SubjectsThe ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all...
Mechanisms of ResistanceIdentification of FosA8, a Plasmid-Encoded Fosfomycin Resistance Determinant from Escherichia coli, and Its Origin in Leclercia adecarboxylataA plasmid-located fosfomycin resistance gene, fosA8, was identified from a CTX-M-15-producing Escherichia coli isolate recovered from urine. Identification of this gene was obtained by whole-genome sequencing. It encoded FosA8, which shares 79% and 78% amino acid identity with the most closely related FosA2 and FosA1 enzymes, respectively. The fosA8...
Experimental TherapeuticsUnexpected Activity of Oral Fosfomycin against Resistant Strains of Escherichia coli in Murine PyelonephritisFosfomycin tromethamine activity is well established for oral treatment of uncomplicated lower urinary tract infections, but little is known about its potential efficacy in pyelonephritis. Ascending pyelonephritis was induced in mice infected with 6 strains of Escherichia coli (fosfomycin MICs, 1 μg/ml to 256 μg/ml). The urine pH was 4.5 before infection and 5.5 to 6....
Clinical TherapeuticsPharmacodynamic Attainment of the Synergism of Meropenem and Fosfomycin Combination against Pseudomonas aeruginosa Producing Metallo-β-LactamaseFosfomycin combined with other antimicrobials has shown good efficacy against multidrug-resistant (MDR) bacteria in both in vitro and clinical studies; however, the activity of fosfomycin combined with other antimicrobials against metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa strains has not been tested. The objective of this study was to...
SusceptibilityEvaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill CurvesThe effects of combining fosfomycin with various antimicrobial agents were evaluated in vitro by broth microdilution checkerboard and time-kill kinetic studies. Checkerboard analyses were used to evaluate the following 30 Gram-negative isolates: 5 Pseudomonas aeruginosa, 5 Acinetobacter baumannii...
Experimental TherapeuticsSmall-Molecule Inhibitor of FosA Expands Fosfomycin Activity to Multidrug-Resistant Gram-Negative PathogensThe spread of multidrug or extensively drug-resistant Gram-negative bacteria is a serious public health issue. There are too few new antibiotics in development to combat the threat of multidrug-resistant infections, and consequently the rate of increasing antibiotic resistance is outpacing the drug development process.
Experimental TherapeuticsThe Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection ModelTreating high-density bacterial infections is a challenging clinical problem. We have a paucity of new agents that can address this problem.
- Mechanisms of ResistanceTet38 Efflux Pump Contributes to Fosfomycin Resistance in Staphylococcus aureus
Fosfomycin inhibits MurA following uptake by the GlpT transporter of glycerol-3-phosphate in Escherichia coli. In Staphylococcus aureus, plasmid overexpression of the Tet38 efflux pump and a glpT mutant resulted in increased MICs and decreased accumulation of fosfomycin, with MICs affected...