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To identify the fosfomycin pharmacokinetic (PK)/pharmacodynamic (PD) index (fT_>MIC, fAUC/MIC or fC_max/MIC) most closely correlated with activity against Pseudomonas aeruginosa and determine the PK/PD target associated with various extents of bacterial killing and the prevention of emergence of resistance.

Dose fractionation was conducted over 24 h in a dynamic one-compartment in vitro PK/PD model utilizing P. aeruginosa ATCC 27853 and two MDR clinical isolates (CR 1005 and CW 7). In total, 35 different dosing regimens were examined across the three strains. Microbiological response was examined by log changes and population analysis profiles. A Hill-type E_max model was fitted to the killing effect data (expressed as the log₁₀ ratio of the area under the cfu/mL curve for treated regimens versus controls).