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Antimicrobial Agents and Chemotherapy, December 2006, p. 3977-3983, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00575-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Treatment and Prevention of Staphylococcus epidermidis Experimental Biomaterial-Associated Infection by Bactericidal Peptide 2{triangledown}

Paulus H. S. Kwakman,1,2 Anje A. te Velde,2 Christina M. J. E. Vandenbroucke-Grauls,1,4 Sander J. H. van Deventer,3 and Sebastian A. J. Zaat1*

Department of Medical Microbiology, CINIMA (Center for Infection and Immunity Amsterdam), Academic Medical Center, University of Amsterdam, Amsterdam,1 Center for Experimental and Molecular Medicine, CINIMA, Academic Medical Center, University of Amsterdam, Amsterdam,2 Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,3 Department of Medical Microbiology and Infectious Diseases, VU Medical Center, Amsterdam, The Netherlands4

Received 10 May 2006/ Returned for modification 17 July 2006/ Accepted 12 September 2006

Biomaterial-associated infections (BAI) are the major cause of failure of indwelling medical devices and are predominantly caused by staphylococci, especially Staphylococcus epidermidis. We investigated the in vitro microbicidal activity of the synthetic antimicrobial peptide bactericidal peptide 2 (BP2) and its efficacy in a murine model of S. epidermidis BAI. BP2 showed potent microbicidal activity at micromolar concentrations against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The staphylocidal activity of BP2 was not affected by physiological salt concentrations and was only slightly affected by the presence of human plasma. In the BAI model, injection of BP2 (5 mg/kg of body weight) 1 h after challenge with S. epidermidis resulted in an 80% reduction in the number of culture-positive implants and a 100-fold reduction in survival of S. epidermidis in peri-implant tissue at 24 h postchallenge. When BP2 was injected along implants 3 h prior to bacterial challenge, the median numbers of CFU cultured from biomaterial implants and peri-implant tissue were reduced by 85% and 90%, respectively. In conclusion, BP2 has potent, broad-spectrum in vitro microbicidal activity and showed potent in vivo activity in a murine model of S. epidermidis biomaterial-associated infection.

* Corresponding author. Mailing address: Department of Medical Microbiology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: 31 20 5664863. Fax: 31 20 6979271. E-mail: s.a.zaat{at}amc.uva.nl.

{triangledown} Published ahead of print on 25 September 2006.

Antimicrobial Agents and Chemotherapy, December 2006, p. 3977-3983, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00575-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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