The Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection Model

摘要: Treating high-density bacterial infections is a challenging clinical problem. We have paucity of new agents that can address this Pseudomonas aeruginosa particularly difficult pathogen to treat effectively because the plethora resistance mechanisms it carries. Fosfomycin an agent discovered circa 40 years ago. Recently, has been resurrected in United States and studied for intravenous therapy. hypothesized that, maximize its utility, would require combination chemotherapy when used circumstance high-bacterial-burden infections. chose examine meropenem plus fosfomycin. These were hollow-fiber infection model. utilized fully factorial study design, looking at 2 doses alone (1 g 8-hourly) two fosfomycin (6 8 8-hourly), as well all possible combinations no-treatment control. high-dimensional model 5 inhomogeneous differential equations with system outputs analyze data simultaneously. Combination therapy outperformed monotherapy regimens, driving >6 log10 CFU/ml killing. was able counterselect emergence (meropenem mutants being killed by combination, combination) regimens studied. The analysis demonstrated significantly synergistic cell killing suppression. Meropenem promising high-burden requires further study.