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Antimicrobial Agents and Chemotherapy, July 2009, p. 2719-2724, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.00047-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Efficacy of Daptomycin in Implant-Associated Infection Due to Methicillin-Resistant Staphylococcus aureus: Importance of Combination with Rifampin{triangledown}

Anne-Kathrin John,1 Daniela Baldoni,1 Manuel Haschke,2 Katharina Rentsch,3 Patrick Schaerli,4 Werner Zimmerli,5 and Andrej Trampuz1,6*

Infectious Diseases, Department of Biomedicine, University Hospital Basel, Basel, Switzerland,1 Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland,2 Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland,3 Infectious Diseases, Transplantation and Immunology, Novartis Pharma Schweiz AG, Bern, Switzerland,4 Basel University Medical Clinic, Kantonsspital, Liestal, Switzerland,5 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland6

Received 13 January 2009/ Returned for modification 26 March 2009/ Accepted 8 April 2009

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 µg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 µg/ml, daptomycin reduced the counts by >3 log10 CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 µg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log10 CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log10 CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

* Corresponding author. Present address: Infectious Diseases Service, Department of Internal Medicine, University Hospital and University of Lausanne (CHUV), Rue du Bugnon 46, Lausanne CH-1011, Switzerland. Phone: 41 21 314 3992. Fax: 41 21 314 28 76. E-mail: andrej.trampuz{at}chuv.ch

{triangledown} Published ahead of print on 13 April 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2719-2724, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.00047-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Steenbergen, J. N., Mohr, J. F., Thorne, G. M. (2009). Effects of daptomycin in combination with other antimicrobial agents: a review of in vitro and animal model studies. J Antimicrob Chemother 64: 1130-1138 [Abstract] [Full Text]  


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