Resistance Selection Studies Comparing the Activity of Razupenem (PTZ601) to Vancomycin and Linezolid against Eight Methicillin-Resistant and Two Methicillin-Susceptible Staphylococcus aureus Strains

Multistep and single-step resistance selection studies were performed with razupenem, linezolid, and vancomycin against 10 methicillin (meticillin)-resistant and -susceptible Staphylococcus aureus strains. After 20 daily subcultures, razupenem yielded only clones with MICs of >4 microg/ml in one strain (8 microg/ml) whose parent's MIC was already 4 microg/ml. After 18 to 49 passages in 6/10 strains, razupenem MICs rose from 0.016 to 2 microg/ml (parents) to 0.125 to 8 microg/ml (with clones stable after 10 drug-free subcultures). Single-step mutant selection frequencies were similarly low for razupenem and comparators.