In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against Staphylococci and Enterococci, including vancomycin- intermediate and -resistant strains

Abstract

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristin-dalfopristin against a variety (n = 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing > or =3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.

FIG. 1

Time-kill experiments performed at four times the MIC against MRSA R499 (A), VISA 992 (B), VRE R588 (E. faecalis) (C), and MRSE R227 (D). Results are means ± standard deviations. GC, growth control; D, daptomycin; V, vancomycin; L, linezolid; Q-D, quinupristin-dalfopristin. MICs of D, V, L, and Q-D, respectively, were as follows: for R499, 0.125, 0.5, 2.0, and 0.25; for 992, 0.5, 8.0, 2.0, and 0.25; for R588, 1.0, 128.0, 4.0, and 2.0; and for R277, 0.25, 1.0, 4.0, and 0.06.

FIG. 2

(A) Time-kill experiments performed with daptomycin in broth and in broth plus pooled human serum (PHS) at four times the MIC against VRE 588. A superscript “A” indicates the MIC determined in SMHB-PCA (MIC, 1.0 μg/ml). A superscript “B” indicates the MIC determined in SMHB-PCA plus PHS (MIC, 2.0 μg/ml). (B) Time-kill experiments performed with daptomycin in broth and in broth plus PHS at four times the MIC against VISA 992. A superscript “A” indicates the MIC determined in SMHB-PCA (MIC, 0.5 μg/ml). A superscript “B” indicates the MIC determined in SMHB-PCA plus PHS (MIC, 1.0 μg/ml).