Vancomycin-resistant Enterococci (VRE) are ESKAPE pathogens and common causes of hospital- acquired infections. Daptomycin (DAP) is front-line therapy; however, defining susceptibility (S) by automated methods may lead to high rates of resistance. Newer agents are available, but roles against VRE are unclear. Our objective was to evaluate DAP S by various testing methods to determine if alternative agents are needed at our center.
Minimum inhibitory concentrations (MICs) were determined by broth- microdilution (BMD). For DAP, MICs were further determined by Etest and Microscan. Oritavancin (ORT) and telavancin (TEL) were supplemented with 0.002% polysorbate-80. VanA and VanB were detected by PCR.
37 E. faecium and 3 E. faecalis were tested. All were vancomycin-R (median MIC = 512 µg/mL) and 93% (37/40) harbored VanA. No isolates harbored VanB. Median (range) MICs for DAP by BMD, Microscan, and Etest were 2 µg/mL (0.25 - 16), 4 (0.5 - >4), and 4 (0.75 - >256), respectively. Associated DAP non-S (NS) rates were 5% (2/40), 26% (10/39), and 45% (18/40), respectively (P= 0.01 [BMD vs Microscan] and P= <0.001 BMD vs Etest]). BMD MICs did not vary among isolates S or NS by other methods. Median (range) MICs were 2 (1 - 8), 0.06 (0.03 - 16), and 0.5 (0.25 – 8) for linezolid (LZD), tigecycline (TGC), and quinupristin/dalfopristin (Q/D), respectively. The corresponding S rates were 93% (37/40), 90% (36/40), and 98% (39/40). Median ORT and TEL MICs were 0.5 (≤0.015 – 8) and 8 (0.12-16), respectively. ORT MICs correlated with vancomycin (r= 0.4949; P= 0.0012) and TEL (r=0.685; P=<0.001) MICs, but not MICs for other agents. ORT MICs were similar against isolates S or NS to other VRE-active agents. 20% (8/40), 40% (16/40), and 68% (27/40) of isolates demonstrated ORT MICs below putative breakpoints of ≤0.12, 0.25, and 0.5, respectively.
Clinicians should be aware that DAP NS rates vary by testing method. Based on DAP BMD data, and retained activity to LZD, TGC, and Q/D, the role for alternative agents is limited. Moreover, ORT MICs correlate with vancomycin and TEL MICs suggesting that cross resistance may occur in at least some VRE isolates. This study underscores the importance of understanding local epidemiology and testing methods to incorporate new agents into clinical practice.
R. V. Marini,
E. G. Press, None
B. A. Potoski, None
C. J. Clancy, None
R. K. Shields, Merck: Grant Investigator , Research support
Astellas: Grant Investigator , Research support