Linezolid Kills Acid Phase and Non-replicative Persister Phase Mycobacterium tuberculosis in a Hollow Fiber Infection Model.

Linezolid Kills Acid Phase and Non-replicative Persister Phase Mycobacterium tuberculosis in a Hollow Fiber Infection Model. Antimicrob Agents Chemother. 2018 Jun 04;: Authors: Drusano GL, Myrick J, Maynard M, Nole J, Duncanson B, Brown D, Schmidt S, Neely M, Scanga CA, Peloquin C, Louie A Abstract The therapy of Mycobacterium tuberculosis (MTB) infection is long and arduous. It has been hypothesized that the therapy duration is driven primarily by populations of organisms in different metabolic states that replicate slowly or not at all (Acid-phase and NRP-phase organisms). Linezolid is an oxazolidinone antimicrobial with substantial activity against Log-phase MTB. Here, we examined organisms in Acid-phase growth and Non-Replicative Persister phenotype growth and determined the effect of differing clinically-relevant exposures to linezolid in a Hollow Fiber Infection Model (HFIM). The endpoints measured were bacterial kill over 29 days and whether organisms less-susceptible to linezolid could be recovered during this period. In addition, we evaluated the effect of administration schedule on linezolid activity, contrasting daily administration with twice the daily dose administered every other day. Linezolid demonstrated robust activity when administered daily against both Acid-phase and NRP-phase organisms. We demonstrated a clear dose response, with 900 mg of linezolid daily generating ≥ 3 Log(CFU/ml) killing of Acid-phase and NR...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research