JAC Advance Access originally published online on March 19, 2009
Journal of Antimicrobial Chemotherapy 2009 63(5):977-981; doi:10.1093/jac/dkp069
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Original research |
Daptomycin pharmacodynamics against Staphylococcus aureus hemB mutants displaying the small colony variant phenotype
1 Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences Buffalo and The New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY 14260, USA 2 Institute of Medical Microbiology, University of Münster, Münster, Germany 3 Roswell Park Cancer Institute, Department of Medicine, Buffalo, NY 14263, USA
Received 5 September 2008; returned 12 December 2008; revised 6 February 2009; accepted 13 February 2009
* Corresponding author. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA. Tel: +1-716-645-2828, ext. 255; Fax: +1-716-645-2886; E-mail: btsuji{at}buffalo.edu
Objectives: Staphylococcus aureus small colony variants (SCVs) are slow-growing morphological variants associated with persistent infections. While vancomycin activity has been shown to be attenuated against SCVs of S. aureus, few data exist regarding daptomycin. The objective was to evaluate the pharmacodynamics of daptomycin against defined S. aureus mutants displaying the SCV phenotype.
Methods: Two S. aureus hemB mutants (Ia48 and III33) displaying the SCV phenotype and their parental strains (COL and Newman) were evaluated. Time–kill experiments were performed using a starting inoculum of 106 cfu/mL at 0, 0.25, 0.5, 1, 2, 4, 8, 16, 32 and 64 times the MIC. Samples were obtained at 0, 1, 2, 4, 6, 8 and 24 h, plated and incubated to determine colony counts. A Hill-type pharmacodynamic mathematical model was fitted to the data to characterize the effect.
Results: Bactericidal activity for daptomycin was achieved and occurred in a concentration-dependent manner against both hemB mutants and their parental strains. Against strains with normal phenotype, bactericidal activity was achieved rapidly, within 2 h at concentrations 
16 times the MIC, while against SCVs, bactericidal activity was achieved within 6 h at concentrations 16 times the MIC. Against both hemB mutants, daptomycin maintained bactericidal activity at 24 h, with similar profiles of killing activity when compared with their parental strains.
Conclusions: Daptomycin achieved bactericidal activity against S. aureus hemB mutants and parenteral isolates. Daptomycin represents a potential therapeutic option for infections caused by S. aureus strains displaying the SCV phenotype and additional studies are warranted.
Keywords: S. aureus , SCVs , cyclic lipopeptide antibiotics
Present address: Wyeth Pharma GmbH, Münster, Wienburgstrasse 207, 48159 Münster, Germany