Enhanced activity of rifalazil in combination with levofloxacin, linezolid, or mupirocin against Staphylococcus aureus in vitro.
Rifalazil is a potent second-generation ansamycin that kills bacterial cells by inhibiting the beta subunit of RNA polymerase. Rifalazil has several improved properties compared with rifampicin, but retains rifampicin's propensity to develop resistant mutants at high frequency. To explore strategies to overcome resistance development, we studied the effects of rifalazil in combination with several different antibiotics in an in vitro time-kill model, against both log phase and stationary phase Staphylococcus aureus cells. Experiments were carried out at high initial cell density so that the frequency and proliferation of resistant mutants could be monitored. We found that each combination was advantageous in terms of enhanced killing and the suppression of mutants, compared with each drug used alone. None of the three combinations was effective against stationary phase cells.
Osburne
Marcia S
MS
ActivBiotics Inc., 110 Hartwell Ave., Lexington, MA 02421, USA. mosburne@mit.edu
Murphy
Christopher K
CK
Rothstein
David M
DM
D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D064704:Levofloxacin; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000494:pharmacology*; D015242:Ofloxacin / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D012294:Rifamycins; C068980:KRM 1648; D064704:Levofloxacin; D015242:Ofloxacin; D016712:Mupirocin; D000069349:Linezolid