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Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin

John, Anne-Kathrin and Baldoni, Daniela and Haschke, Manuel and Rentsch, Katharina and Schaerli, Patrick and Zimmerli, Werner and Trampuz, Andrej. (2009) Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin. Antimicrobial agents and chemotherapy : AAC, Vol. 53. pp. 2719-2724.

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Official URL: http://edoc.unibas.ch/dok/A6006347

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Abstract

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 microg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 microg/ml, daptomycin reduced the counts by <3 log(10) CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 microg/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 log(10) CFU/ml, whereas in combination with rifampin, a reduction in the counts of <6 log(10) 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Allgemeine innere Medizin Liestal (Zimmerli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Allgemeine innere Medizin Liestal (Zimmerli)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Infektiologie > Infektiologie (Battegay M)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Infektiologie > Infektiologie (Battegay M)
UniBasel Contributors:Zimmerli, Werner and Trampuz, Andrej
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:11

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