Comparison of the in vivo efficacy of ceftaroline fosamil, vancomycin and daptomycin in a murine model of methicillin-resistant Staphylococcus aureus bacteraemia

The need for alternative drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia has led to a focus on ceftaroline, for which clinical data remain scarce. Herein, the efficacy of ceftaroline fos-amil for the treatment of experimental MRSA bacteraemia was compared with that of approved therapies. Five MRSA strains were tested in an immunocompetent BALB/c bacteraemia model. Serum pharmacoki-netics of ceftaroline fosamil were determined using HPLC/MS Q-TOF. Two hours after infection with the MRSA strains, mice were administered 50 mg/kg of ceftaroline fosamil every 6 h, for 24 h. This regi-men yielded a T > MIC of 61.5% for an MIC of 1 mg/L and proved efficacious against all strains, including an hVISA strain with non-susceptibility to daptomycin, as indicated by the reduction (mean & PLUSMN; s.d.) in log10 CFU/mL in blood of 2.34 & PLUSMN; 0.33 and log10 CFU/g in kidney of 2.08 & PLUSMN; 0.22. Similarly, treatment with daptomycin yielded a log reduction of 2.30 & PLUSMN; 0.60 in blood and 2.14 & PLUSMN; 0.31 in kidney. The decrease in bacterial density was less accentuated after treatment with vancomycin, which yielded 1.84 & PLUSMN; 0.73 and 1.95 & PLUSMN; 0.32 log reductions in blood and kidney, respectively. The results of the study showed that the ef-ficacy of ceftaroline fosamil against MRSA bacteraemia in mice is not inferior to that of vancomycin and daptomycin, and indicated the potential use of ceftaroline fosamil against difficult-to-treat S. aureus bac-teraemia. Considering these promising data, clinical trials should be conducted to ascertain the efficacy of the drug for treating bloodstream infections in humans. & COPY; 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.