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J Antimicrob Chemother. 2013 Mar;68(3):644-7. doi: 10.1093/jac/dks453. Epub 2012 Nov 14.

Evaluation of the combination of daptomycin and nafcillin against vancomycin-intermediate Staphylococcus aureus.

Author information

1
Northeastern University, Bouvé College of Health Sciences, School of Pharmacy, 360 Huntington Ave, R218 TF, Boston, MA 02115, USA. s.leonard@neu.edu

Abstract

OBJECTIVES:

Continued selective pressure from glycopeptide use has led to non-susceptible strains of Staphylococcus aureus, including vancomycin-intermediate S. aureus (VISA). Though relatively uncommon, VISA presents a particularly difficult clinical challenge when it arises. Pertinent to this investigation is the correlation between vancomycin intermediacy and daptomycin non-susceptibility. The aim of this study was to evaluate the potential for synergy between daptomycin and nafcillin against VISA.

METHODS:

Twenty VISA strains were evaluated for daptomycin and nafcillin MICs by broth microdilution in duplicate. Potential for synergy was assessed by time-kill at 0.5× MIC in triplicate. Four strains displaying synergy in time-kill analysis were analysed in an in vitro pharmacokinetic (PK)/pharmacodynamic (PD) model in duplicate over 72 h.

RESULTS:

In time-kill experiments, 55% of strains (11/20) displayed synergy with the combination. In the PK/PD model, no differences between daptomycin-alone and combination regimens were observed for the strain with the lowest daptomycin MIC (0.5 mg/L). For the strain with a daptomycin MIC of 1 mg/L, 6 mg/kg daptomycin+nafcillin was superior to 6 mg/kg daptomycin alone (P=0.002) and 10 mg/kg daptomycin+nafcillin was superior to all other regimens (P ≤ 0.004). When the daptomycin MIC increased to 2 mg/L, 10 mg/kg daptomycin+nafcillin was superior to 6 mg/kg daptomycin+nafcillin, which was superior to both 6 and 10 mg/kg daptomycin alone (P ≤ 0.019).

CONCLUSIONS:

Daptomycin and nafcillin in combination significantly improved antibacterial activity against VISA. This effect was more pronounced as the daptomycin susceptibility of the strain declined.

PMID:
23152482
DOI:
10.1093/jac/dks453
[Indexed for MEDLINE]

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