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Antimicrobial Agents and Chemotherapy, September 2005, p. 3789-3793, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3789-3793.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intensive Therapy with Ceftobiprole Medocaril of Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus

Pierre Vaudaux,* Asllan Gjinovci, Manuela Bento, Dongmei Li, Jacques Schrenzel, and Daniel P. Lew

Service of Infectious Diseases, University Hospitals of Geneva, CH-1211 Geneva 14, Switzerland

Received 16 February 2005/ Returned for modification 2 April 2005/ Accepted 18 June 2005

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 µg/ml, respectively. In vitro elimination rates of strain MRGR3 of 4 and 8 µg/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 ≥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.

* Corresponding author. Mailing address: Service of Infectious Diseases, University Hospitals of Geneva, 24 rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. Phone: 41-22 372 9826. Fax: 41-22 372 9830. E-mail: Pierre.Vaudaux{at}hcuge.ch.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3789-3793, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3789-3793.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vaudaux, P., Fleury, B., Gjinovci, A., Huggler, E., Tangomo-Bento, M., Lew, D. P. (2009). Comparison of Tigecycline and Vancomycin for Treatment of Experimental Foreign-Body Infection Due to Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 3150-3152 [Abstract] [Full Text]  
  • Yin, L.-Y., Calhoun, J. H., Thomas, J. K., Shapiro, S., Schmitt-Hoffmann, A. (2008). Efficacies of Ceftobiprole Medocaril and Comparators in a Rabbit Model of Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 1618-1622 [Abstract] [Full Text]  
  • Arias, C. A., Singh, K. V., Panesso, D., Murray, B. E. (2007). Evaluation of ceftobiprole medocaril against Enterococcus faecalis in a mouse peritonitis model. J Antimicrob Chemother 60: 594-598 [Abstract] [Full Text]  


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