ceftobiprole and Foreign-Bodies

Antibiotic therapy is essential in foreign body associated infections. The treatment regime should aim at high tissue concentrations, high bioavailability, high biofilm penetration and good tolerance. We investigated whether the new cephalosporin ceftobiprole is active against clinical isolates from musculoskeletal foreign body associated infections. One hundred ninety-six staphylococci isolates (coagulase negative staphylococci and Staphylococcus aureus) derived from foreign body associated infections were tested towards susceptibility to ceftobiprole, using a test strip assay and broth microdilution. The MIC for all strains S. aureus indicated susceptibility to ceftobiprole. The MIC of only two strains of coagulase negative staphylococci was above 2 mg/L. Our results show that ceftobiprole might be considered as an off-label treatment option in foreign body associated infections.

Topics: Anti-Bacterial Agents; Cephalosporins; Foreign Bodies; Humans; Microbial Sensitivity Tests; Prosthesis-Related Infections; Staphylococcal Infections; Staphylococcus

The therapeutic activity of ceftobiprole medocaril, the water-soluble prodrug of ceftobiprole, was compared to that of vancomycin in a rat tissue cage model of chronic methicillin-resistant Staphylococcus aureus (MRSA) foreign-body infection. The MICs and MBCs of ceftobiprole and vancomycin in Mueller-Hinton broth for strain MRGR3 were 1 and 4 and 1 and 2 microg/ml, respectively. In vitro elimination rates of strain MRGR3 of 4 and 8 microg/ml of ceftobiprole or vancomycin were equivalent. After 2 weeks of infection, mean +/- standard error of the mean viable counts of strain MRGR3 were 6.83 +/- 0.11 log CFU/ml of tissue cage fluid (n = 87). High-dose regimens of ceftobiprole medocaril (equivalent to 150 mg/kg of ceftobiprole) or 50 mg/kg vancomycin produced nearly identical average peak and trough levels of ceftobiprole and vancomycin in tissue cage fluid, which exceeded the MBC of either antibiotic towards strain MRGR3 for > or =75% of each dosing interval. After 7 days of therapy with ceftobiprole medocaril or vancomycin, average counts of MRGR3 decreased significantly (P < 0.02) by 0.68 +/- 0.28 (n = 29) and 0.88 +/- 0.22 (n = 28) log CFU/ml of tissue cage fluid, respectively, compared with cages of untreated animals, but were not significantly different from each other. No resistant mutants were detected on ceftobiprole-supplemented agar following therapy with this cephalosporin. The in vivo activity of ceftobiprole medocaril against chronic MRSA foreign-body infections was equivalent to that of vancomycin and did not lead to the emergence of resistant subpopulations.

Topics: Animals; Cephalosporins; Foreign Bodies; Methicillin Resistance; Microbial Sensitivity Tests; Mutation; Rats; Rats, Wistar; Staphylococcal Infections; Staphylococcus aureus; Vancomycin