Abstract
Mycobacterium abscessus complex consist of three rapidly growing subspecies: M. abscessus, M. massiliense, and M. bolletii. They are clinically important human pathogens responsible for opportunistic pulmonary and skin and soft tissue infections. Treatment of M. abscessus infections is difficult due to in vitro resistance to most antimicrobial agents. Tedizolid (TZD) is a next-generation oxazolidinone antimicrobial with a wide spectrum of activity even against multidrug resistant Gram-positive bacteria. In this study, the in vitro activity of TZD against the M. abscessus complex (n = 130) was investigated. Susceptibility testing by broth microdilution showed lower TZD minimum inhibitory concentrations (MICs) when compared to linezolid. The MIC50 and MIC90 was 1 mg/L and 4 mg/L, respectively across all M. abscessus complex members, reflecting no difference in subspecies response to TZD. Pre-exposure of M. abscessus complex to subinhibitory concentrations of TZD did not trigger any inducible drug resistance. Single-drug time kill assays and bactericidal activity assays demonstrated bacteriostatic activity of TZD in all three M. abscessus subspecies, even at high drug concentrations of 4 to 8x MIC. Combination testing of TZD with clarithromycin, doxycycline and amikacin using the checkerboard approach showed no antagonistic interactions. TZD may be an effective therapeutic antimicrobial agent for the treatment of M. abscessus infections.
Highlights
Mycobacterium abscessus complex consists of three rapidly-growing mycobacteria (RGM) subspecies: M. abscessus subspecies abscessus, M. abscessus subspecies massiliense and M. abscessus subspecies bolletii (Lee et al, 2015)
We explored the potential use of TZD for anti-mycobacterial therapy by characterizing the in vitro activity of TZD against 130 clinical isolates of M. abscessus complex members
To examine if a similar inducible phenomenon existed for TZD, M. abscessus complex isolates were pre-exposed to sub-inhibitory concentrations of TZD prior to minimum inhibitory concentrations (MICs) determination as previously described (Aziz et al, 2017)
Summary
Mycobacterium abscessus complex consists of three rapidly-growing mycobacteria (RGM) subspecies: M. abscessus subspecies abscessus, M. abscessus subspecies massiliense and M. abscessus subspecies bolletii (Lee et al, 2015). They have emerged as clinically important multi-drug resistant (MDR) human pathogens responsible for a wide spectrum of skin and soft tissue infections (SSTIs), opportunistic infections in immunocompromised patients and pulmonary infections in patients with chronic pulmonary disease or cystic fibrosis (Nessar et al, 2012). M. abscessus pulmonary infections are infamously difficult to treat, with low cure rates ranging from 30 to 50% This is attributed to natural resistance to most antimicrobial agents (Van Ingen et al, 2012). We explored the potential use of TZD for anti-mycobacterial therapy by characterizing the in vitro activity of TZD against 130 clinical isolates of M. abscessus complex members
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