Antibiotic heteroresistance in Mycobacterium tuberculosis isolates: a systematic review and meta-analysis.

Background: Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance (HR)-the presence of resistant and susceptible isolates among MTB strains- has been reported from around the world. This phenomenon can lead to full resistance development and treatment failure.

Methods: We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until October 21, 2020). The study outcomes revealed the weighted pooled prevalence of antibiotic HR in MTB isolates with subgroup analysis by year, quality of study, and heteroresistance detection method.

Results: A total of 38 studies which had investigated MTB isolates were included in the meta-analysis. Geographically, the highest number of studies were reported from Asia (n  =  24), followed by Africa (n  =  5). Nineteen studies reported HR to isoniazid, with a weighted pooled prevalence of 5% (95% CI 0-12) among 11,761 MTB isolates. Also, there is no important trend for the subgroup analysis by the study period (2001-2014 vs 2015-2017 vs 2018-2020). HR to rifampin was reported in 17 studies, with a weighted pooled prevalence of 7% (95% CI 2-14) among 3782 MTB isolates. HR to fluoroquinolone and ethambutol were reported in 12 and 4 studies, respectively, with weighted pooled prevalence of 10% and 1% among 2153 and 1509 MTB isolates, correspondingly.

Conclusion: Based on our analysis, HR in MTB isolates with different frequency rate is present worldwide. Thus, the selection of appropriate and reliable methods for HR detection is crucial for TB eradication.