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

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 susce...

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Main Authors: Wenli Wang, Hongjuan Zhou, Long Cai, Tingting Yang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Global Antimicrobial Resistance
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213716524004569
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author Wenli Wang
Hongjuan Zhou
Long Cai
Tingting Yang
author_facet Wenli Wang
Hongjuan Zhou
Long Cai
Tingting Yang
author_sort Wenli Wang
collection DOAJ
description 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.
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spelling doaj-art-25e5d605f95f426aa16373e31a41de3e2025-02-08T05:00:27ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-01-01405361Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysisWenli Wang0Hongjuan Zhou1Long Cai2Tingting Yang3Clinical Laboratory Experiment Center, Hangzhou Red Cross Hospital, Hangzhou, ChinaClinical Laboratory Experiment Center, Hangzhou Red Cross Hospital, Hangzhou, ChinaClinical Laboratory Experiment Center, Hangzhou Red Cross Hospital, Hangzhou, ChinaCorresponding author. Mailing address: Tingting Yang, Clinical Laboratory Experiment Center, Hangzhou Red Cross Hospital No. 208 East Huancheng Road, Hangzhou, 310003, China.; Clinical Laboratory Experiment Center, Hangzhou Red Cross Hospital, Hangzhou, ChinaObjective: 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.http://www.sciencedirect.com/science/article/pii/S2213716524004569Mycobacterium tuberculosisRifampicin resistance mutationRifabutin-susceptibleDrug susceptibility testMinimum inhibition concentration
spellingShingle Wenli Wang
Hongjuan Zhou
Long Cai
Tingting Yang
Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
Journal of Global Antimicrobial Resistance
Mycobacterium tuberculosis
Rifampicin resistance mutation
Rifabutin-susceptible
Drug susceptibility test
Minimum inhibition concentration
title Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
title_full Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
title_fullStr Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
title_full_unstemmed Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
title_short Association between the rifampicin resistance mutations and rifabutin susceptibility in Mycobacterium tuberculosis: A meta-analysis
title_sort association between the rifampicin resistance mutations and rifabutin susceptibility in mycobacterium tuberculosis a meta analysis
topic Mycobacterium tuberculosis
Rifampicin resistance mutation
Rifabutin-susceptible
Drug susceptibility test
Minimum inhibition concentration
url http://www.sciencedirect.com/science/article/pii/S2213716524004569
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