In vitro pharmacodynamics of fosfomycin against clinical isolates of Pseudomonas aeruginosa

摘要: Background The use of fosfomycin for treatment systemic infections due to MDR Pseudomonas aeruginosa is increasing. However, pharmacodynamic data are limited. Methods Sixty-four clinical isolates P. (MDR and non-MDR) from two Australian hospitals were collected; 59 patients with cystic fibrosis 5 critically ill patients. in vitro properties (disodium) investigated via MICs (all isolates) and, selected isolates, time-kill kinetics (static dynamic models; concentration range, 1-1024 mg/L), population analysis profiles (PAPs) post-antibiotic effect (PAE). Two inocula (∼10(6) ∼10(8) cfu/mL) included static studies examine the on bacterial killing. Results ranged 1 >512 mg/L, 61% considered susceptible (MIC ≤64 mg/L). MIC distributions non-MDR similar. Baseline PAPs indicated heteroresistance all tested. Time-kill showed moderate (maximum killing ∼3 log10 cfu/mL), time-dependent at low inoculum regrowth 24 h. Most concentrations resulted complete replacement fosfomycin-susceptible colonies by fosfomycin-resistant colonies. Bacterial was virtually eliminated high inoculum. PAE 0.3 5.5 Conclusions These suggest monotherapy may be problematic caused aeruginosa. Further investigation combination therapy warranted.