Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy.

摘要: There has been a resurgence of interest in aerosolization antibiotics for treatment patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships these drugs have not fully characterized. The aim this study was to describe individual and combined antibacterial effects simulated epithelial lining fluid exposures aerosolized amikacin fosfomycin against resistant isolates Pseudomonas aeruginosa (MICs 16 mg/liter 64 mg/liter) Klebsiella pneumoniae 2 using dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations 300 and/or 1,200 as 12-hourly dosing regimens were used. Quantitative cultures performed changes total bacterial populations. targeted starting inoculum 108 CFU/ml both strains. We observed that neither nor monotherapy bactericidal P. while associated rapid amplification strains (about 109 within 24 48 h). For K. pneumoniae, but bactericidal. When combined, killing (6-log kill Furthermore, effectively suppressed growth In conclusion, effective at maximizing suppressing emergence resistance isolates.