Resistance Studies with Daptomycin

Abstract

We studied the in vitro emergence of resistance to daptomycin using three methods: spontaneous resistance incidence, serial passage in the presence of increasing drug concentrations, and chemical mutagenesis. No spontaneously resistant mutants were obtained for any organism tested (−10 for Staphylococcus aureus , −9 for Staphylococcus epidermidis , −9 for Enterococcus faecalis , −9 for Enterococcus faecium , 12.5 μg/ml) had significant growth defects but did not display phenotypes typical of S. aureus small colony variants. The voltage component (Δψ) of the bacterial membrane potential was increased in three independent resistant isolates. In vivo data showed that some daptomycin-resistant mutants had lost significant virulence. For other mutants, the degree of in vitro resistance was greater than the change in in vivo susceptibility. These results suggest that infection with some daptomycin-resistant organisms may still be easily treatable.