Correcting for Antimicrobial Testing Methodology Reveals Temporary Decline in Daptomycin MIC Following Intervention

Susceptibility of vancomycin-resistant Enterococcus (VRE) to daptomycin has significant treatment implications. Following an observed hospital-wide increase in daptomycin minimal inhibitory concentration (MIC) for VRE faecium blood stream infections (BSI) between 2011 and 2014 in a tertiary care hospital, the hospital guidelines were modified to prefer linezolid over daptomycin for VRE faecium BSI. Infection prevention efforts targeted at VRE were continued throughout this time. A decrease in daptomycin MICs was observed in 2015, which also coincided with a change in MIC testing method from Etest to the Trek system. Daptomycin MIC data were abstracted retrospectively for all VRE faecium BSI initial isolates (n = 293) between 2011 and 2016 from a 1,000-bed tertiary care hospital. Daptomycin MICs for all stored initial Enterococcus BSI isolates between September 2013 and September 2016 (n = 309) were retested using the Etest method. The corrected trend of daptomycin MICs was generated by applying a correction factor to each MIC, calculated as the mean fold change from the original to the retest value according to original test method. Essential agreement (± one 2-fold dilution) between our repeated Etest and the original MIC was 98.2 and 98.0% for Etest and Trek, respectively. Categorical agreement was lower at 90.2% and 93.9%, reflecting the large number of isolates within one dilution of the breakpoint. The fold difference in initial MIC to retested MIC differed significantly by initial test type (χ2 = 76.38, df = 9, P < 0.005). Samples initially test by Etest were on average 0.25 fold lower than their initial result, while samples initially tested on Trek were on average 0.48 fold higher upon retesting. Correction for testing method reduced the magnitude of the peak and trough in the MIC trend, however a decrease in MIC in 2015 was still observed, followed by an unexplained increase in 2016. VRE faecium MICs to daptomycin decreased when daptomycin use was reduced, but subsequently rose despite lower daptomycin use and continued infection prevention measures. Incorporating the effect of changes to antimicrobial susceptibility testing is critical to monitoring hospital trends and interpreting effects of interventions. T. Patel, Merck: Grant Investigator, Research grant.