Synergistic effects of aminoglycosides and fosfomycin on Pseudomonas aeruginosa in vitro and biofilm infections in a rat model

Objectives: To study the in vitro and in vivo efficacy of aminoglycosides against Pseudomonas aeruginosa, either alone or in combination with fosfomycin. Methods: Using an in vitro study to assess inhibition of the growth of P. aeruginosa, MIC90 and MIC50 values of amikacin, gentamicin, netilmicin, tobramycin and isepamicin were determined, either alone or in combination with fosfomycin, and then the fractional inhibitory concentration index was calculated. In the biofilm-infected rat model, the efficacy and effects of treatment with isepamicin and fosfomycin on infection were studied. Results: The combinations of amikacin and fosfomycin or isepamicin and fosfomycin showed the most significant synergistic effects against P. aeruginosa as compared with other treatments. In the biofilm-infected rat model, as a single agent, neither isepamicin nor fosfomycin reduced C-reactive protein level and numbers of white blood cells, or reduced the colony counts of the bacteria from both tissue and silica gel tubes. However, the combination of these two agents resulted in a good therapeutic effect. Conclusions: Combination of aminoglycosides and fosfomycin not only showed a positive effect in vitro but also improved the therapeutic effect in a biofilm-infected rat model. This offers an effective treatment strategy against some therapy-resistant infections.