Assessing the Emergence of Resistance in vitro and Invivo: Linezolid Combined with Fosfomycin Against Fosfomycin-Sensitive and Resistant .

Purpose: We aimed to evaluate the synergistic effect of linezolid and fosfomycin on fosfomycin-sensitive and -resistant clinical isolates in vitro and in vivo and whether the emergence of fosfomycin resistance in is associated with changes in strain virulence, from the perspective of fitness cost.

Methods: The synergistic effect of linezolid and fosfomycin was studied via in vitro checkerboard and static time-kill assays, as well as based on the in vivo survival rate and hemolymph load of a infection model. Fosfomycin resistance was induced via a stepwise increase in concentration.

Factorial design and post-antibiotic sub-MIC effects of linezolid combined with fosfomycin against vancomycin-resistant enterococci.

Background: Antimicrobial drug resistance, including vancomycin-resistant enterococci (VRE), has long been an inescapable clinical problem. If vancomycin loose its therapeutic relevance, a regimen of linezolid combined with fosfomycin may provide an alternative option.

Methods: In this study, the antimicrobial effect of linezolid combined with fosfomycin on several different types of VRE was investigated using a checkerboard method and time-kill assays.

Pharmacodynamics of Linezolid Plus Fosfomycin Against Vancomycin-Resistant in a Hollow Fiber Infection Model.

The optimal therapy for severe infections caused by vancomycin-resistant (VREfm) remains unclear, but the combination of linezolid and fosfomycin may be a good choice. The 24-h static-concentration time-kill study (SCTK) was used to preliminarily explore the pharmacodynamics of linezolid combined with fosfomycin against three clinical isolates. Subsequently, a hollow-fibre infection model (HFIM) was used for the first time to further investigate the pharmacodynamic activity of the co-administration regimen against selected isolates over 72 h.

Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model.

Background: Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic.

Methods: In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro.

Dose Optimization of Combined Linezolid and Fosfomycin against by Using an Pharmacokinetic/Pharmacodynamic Model.

The rapid spread of antibiotic resistance among has prompted considerable interest in determining the dosage regimen of linezolid combined with fosfomycin. A checkerboard assay was employed to evaluate whether linezolid combined with fosfomycin had a synergistic effect on isolates from the hospital, including three drug-resistant strains (MIC of linezolid [MIC], ≥8 mg/L; MIC of fosfomycin [MIC], ≥256 mg/L). The static time-kill assay, dynamic pharmacokinetic (PK)/pharmacodynamic (PD) model, and semimechanistic PK/PD model were used to explore and predict effective combined dosage regimens.