Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistantStaphylococcus aureus (MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108 to 5 × 108 CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n = 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n = 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106 CFU/g of bone) and the vancomycin group (median, 3.03 × 105 CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102 and 1.51 × 103 CFU/g of bone). Vancomycin was superior to the no-drug control (P = 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P < 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103 CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103 CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P = 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P < 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.