In vitro time-kill activities of rifalazil, alone and in combination with vancomycin, against logarithmic and stationary cultures of Staphylococcus aureus.
Rifalazil is a novel rifamycin that, like other members of this class, inhibits bacterial transcription by targeting the beta subunit of prokaryotic DNA-dependent RNA polymerase. To address the high-frequency resistance seen with rifamycins, we assessed the ability of rifalazil, alone and in combination with vancomycin, to both kill cells and to suppress the appearance of resistant mutants in log and stationary phase Staphylococcus aureus cultures, using high cell densities in an in vitro kill curve model. We found that (1) rifalazil alone killed log-phase cultures more rapidly than rifampicin, but both drugs quickly selected for resistant mutants, (2) co-treatment of log phase cultures with rifalazil and vancomycin increased bacterial killing by about 3-Log10 over either drug used alone and delayed the appearance of rifamycin-resistant mutants, (3) rifalazil and vancomycin in combination killed stationary phase cultures
Osburne
Marcia S
MS
ActivBiotics Inc., 128 Spring St., Lexington, MA 02421, USA. mosburne@mit.edu
Rothstein
David M
DM
Farquhar
Ronnie
R
Murphy
Christopher K
CK
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004351:Drug Resistance; D008826:Microbial Sensitivity Tests; D012294:Rifamycins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D012294:Rifamycins; C068980:KRM 1648; D014640:Vancomycin