Abstract
We evaluated the combined effects of fosfomycin (FOM) with β-lactam antibiotics, including cefepime (CFPM), cefotaxime (CTX), cefminox (CMNX), cefotiam (CTM), cefazolin (CEZ), imipenem (IPM) and benzylpenicillin (PCG), against clinically-isolated penicillin-resistantStreptococcus pneumoniae (PRSP) based on fractional inhibitory concentration (FIC) indices. The combination of FOM and the β-lactam antibiotics showed synergy and partial synergy against 70% to 90% of the 56 PRSP strains tested. Moreover, FOM combined with CTM, CMNX and PCG showed synergy against 35.7%, 58.9%, and 30.4% of strains, respectively. MIC80s of the β-lactam antibiotics in combination with FOM, using the lowest concentrations clinically achievable in cerebrospinal fluid, were several times lower than those of each β-lactam antibiotic alone. The bactericidal activities of FOM and the β-lactam antibiotics against PRSP were greater when the 2 agents were added simultaneously than when added sequentially. The PBP profiles of PRSP exposed to a low concentration of FOM combined with CFPM, CTX, IPM or PCG were evaluated. In combination with FOM and any one of these β-lactam antibiotics, the binding of [14C]-PCG on all PBPs of a given PRSP strain was reduced in comparison with that in the presence of FOM or a β-lactam antibiotic alone.
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Totsuka, K., Uchiyama, T., Shimizu, K. et al. In vitro combined effects of fosfomycin and β-lactam antibiotics against penicillin-resistantStreptococcus pneumoniae . J Infect Chemother 3, 49–54 (1997). https://doi.org/10.1007/BF02489184
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DOI: https://doi.org/10.1007/BF02489184