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Journal Article
|Research

Effectiveness of a bedaquiline, linezolid, clofazimine “core” for multidrug-resistant tuberculosis

Zeng C, Hernán MA, Trevisi L, Sauer S, Mitnick CD, Hewison C, Bastard M, Khan P, Seung KJ, Rich ML, Law S, Kikvidze M, Kirakosyan O, Miankou A, Thit P, Mamsa S, Janmohamed A, Melikyan N, Ahmed S, Vargas D, Binegdie AB, Temirova K, Oyewusi L, Philippe K, Vilbrun SC, Khan U, Huerga H, Franke MF
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Abstract

RATIONALE


Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients.


OBJECTIVES


We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline.


METHODS


We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment.


MEASUREMENTS AND MAIN RESULTS


Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41).


CONCLUSIONS


High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.

Subject Area

tuberculosisantimicrobial resistance

Collections

The endTB project

Languages

English
DOI
10.1101/2024.01.18.24301453
Published Date
20 Jan 2024
PubMed ID
38293100
Journal
medRxiv
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Effectiveness of a bedaquiline, linezolid, clofazimine “core” for multidrug-resistant tuberculosis | Journal Article / Research | MSF Science Portal