Clofazimine susceptibility testing of Mycobacterium avium complex and Mycobacterium abscessus: a meta-analysis study

The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not sufficiently effective against nontuberculous mycobacteria (NTM) and there is a need for new drugs. This study aimed to estimate the overall in vitro activity of clofazimine (CFZ) against MAC and MABS clinical isolates.

We systematically searched four databases up to 1 March 2020 to identify relevant studies. Studies were included if they used the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). We assessed the pooled in vitro CFZ resistance rate in MAC and MABS clinical isolates using a random- effects model. Sources of heterogeneity were evaluated using Cochran's Q and the I² statistic. Potential for publication bias was explored using Begg's and Egger's tests. All analyses were conducted using Stata 14.0.

A total of 20 publications (11 reports for MAC and 15 for MABS) were included. The pooled rates of in vitro resistance to CFZ in clinical isolates of MAC and MABS were 9.0% [95% confidence interval (CI) 3.0-17.0%] and 16.0% (95% CI 4.0-34.0%), respectively. There was no evidence of publication bias.

This study reports the frequency of CFZ resistance in clinical isolates of MAC and MABS. According to the results, establishing accurate DST methods for detecting CFZ resistance, performing DST for all NTM isolates to provide effective treatment, and continuous monitoring of drug resistance are suggested for the prevention and control of CFZ-resistant NTM.