Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis

Abstract

Objective

Certain rifampicin-resistant Mycobacterium tuberculosis (MTB) strains are susceptible to rifabutin (RFB) and may be amenable to RFB treatment. We performed a meta-analysis of available cross-sectional studies to determine the rifampicin (RIF) resistance mutations associated with RFB susceptibility.

Methods

We identified studies through PubMed, Web of Science, Embase, and the Cochrane Library up to September 30, 2024. Studies that investigated RpoB mutations and reported phenotypic drug susceptibility to RIF and RFB met our criteria. The relationship between RIF-resistance mutations to RFB-susceptibility was evaluated using odds ratios (OR).

Results

Twenty-seven studies comprised 9222 clinical RIF-resistant MTB strains from 25 countries met the inclusion criteria. Of these strains, 14.93% (1377/9222) were susceptible to RFB. We found that 14 RIF-resistance mutations were associated with susceptibility to RFB. Among these, nine had high confidence (OR>10) in predicting RFB susceptibility: RpoB D435V, H445L, D435Y, D435F, S441L, L430P, H445G, S441Q, L430R. Among the strains carrying these mutations, 59.04% (702/1189) were susceptible to RFB. The ratio increased to 83.45% in studies following CLSI guidelines. The minimum inhibition concentrations (MICs) of these mutations revealed that they had low MIC to RFB and exhibited a lack of correlation between MICs for RIF and RFB. L452P, I491F, H445C, H445N, and D435G exhibited moderate confidence (5<OR≤10) in predicting susceptibility to RFB. S450L and S450W were associated with RFB-resistance (OR<1).

Conclusions

These results provide a theoretical basis for the molecular detection of RFB-susceptible tuberculosis and alternative treatment with RFB in patients with multidrug-resistant/rifampicin-resistant tuberculosis.