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Intracellular activity of antibiotics against Staphylococcus aureus internalised human skin keratinocytes: comparison with THP-1 macrophages

Abstract number: O143

Lemaire S., Van Bambeke F., Pirnay J.P., Verween G., De Corte P., De Vos D., Tulkens P.M.

Objectives: Relapsing and chronic S. aureus infections has been ascribed to intracellular persistence. While the activity of antibiotics against S. aureus in macrophages has already been extensively studied, little is known in keratinocytes. We examine here the activity of antibiotics commonly used for the treatment of SSSI infections (oxacillin, vancomycin, linezolid, rifampicin) and of more recently approved ones (quinupristin-dalfopristin, daptomycin, moxifloxacin) in a model of human keratinocytes in comparison to human macrophages.

Methods: We used a fully susceptible S. aureus strain (ATCC 25923). MICs were determined by broth microdilution. Infection of human skin keratinocytes and THP-1 macrophages was performed following published methods (Br. J. Dermatol. 2002; 146:943–51; AAC 2006;50:841–51). Activity was measured after 24 h of exposure to a wide range of drug extracellular concentrations and data [change in log CFU vs. log of extracell. conc.] analysed using a pharmacological dose-response model (Hill equation).

Results: The table shows MICs values. Sigmoidal dose-responses were seen for al drugs (R2 > 0.9) and allowed to calculate static concentrations (SC) and Emax values.

Conclusions: Pharmacological parameters were similar in both cell types for all drugs (except rifampicin, which showed higher Emax and lower static concentration in keratinocytes). The data extend to keratinocytes the poor activity of oxacillin, vancomycin and linezolid seen against intracellular S. aureus in macrophages. They also suggest to further assess the potential advantages offered in this context by daptomycin, moxifloxacin, quinupristin/dalfopristin, and rifampicin.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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