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Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

ABSTRACT: Background: Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR-TB); however, there are limited data guiding their use and no comparison studies.

Methods: We conducted a prospective, observational study among patients with MDR-TB in Georgia who were receiving a bedaquiline- or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation and super learning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen.

Results: Among 156 patients with MDR-TB, 100 were enrolled and 95 were receiving a bedaquiline-based (n = 64) or delamanid-based (n = 31) regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine, and a fluoroquinolone. The median numbers of effective drugs received among patients on bedaquiline-based (4; interquartile range [IQR], 4-4) and delamanid-based (4; IQR, 3.5-5) regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs 10%, respectively; P < .01). Adjusted rates of sputum culture conversion at 2 months (67% vs 47%, respectively; P = .10) and 6 months (95% vs 74%, respectively; P < .01), as well as more favorable clinical outcomes (96% vs 72%, respectively; P < .01), were higher among patients receiving bedaquiline versus delamanid.

Conclusions: Among patients with MDR-TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion, more favorable outcomes, and a lower rate of acquired drug resistance versus delamanid-based regimens.

SUBMITTER: Kempker RR

PROVIDER: S-EPMC7713674 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

Kempker R R RR Mikiashvili L L Zhao Y Y Benkeser D D Barbakadze K K Bablishvili N N Avaliani Z Z Peloquin C A CA Blumberg H M HM Kipiani M M

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20201201 9

<h4>Background</h4>Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR-TB); however, there are limited data guiding their use and no comparison studies.<h4>Methods</h4>We conducted a prospective, observational study among patients with MDR-TB in Georgia who were receiving a bedaquiline- or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary out ...[more]

PMID: 31712809

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Project description:BackgroundThe bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.MethodsWe enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated.ResultsA total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups.ConclusionsA total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.).

Dataset Information

Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

Publications

Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens.

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