Abstract
In 2019, the Clinical and Laboratory Standards Institute revised the daptomycin breakpoints for Enterococcus spp. twice in rapid succession. Analyses leading to these revisions included review of testing issues, murine and human in vivo pharmacodynamics, safety of off-label doses, and treatment outcomes. The data review brought up a dilemma that is encountered with increasing frequency: a breakpoint supported by pharmacokinetic/pharmacodynamic modeling that bisected the wild-type Enterococcus faecium MIC distribution. In such instances, not only does the probability of pharmacokinetic/pharmacodynamic targets need to be taken into account but also the probability that the laboratory can generate an accurate MIC that is reproducible within one interpretive category.