The ERS-endorsed official ATS/CDC/IDSA clinical practice guidelines on treatment of drug-susceptible tuberculosis

Sotgiu, Giovanni; Nahid, Payam; Loddenkemper, R.; Abubakar, Ibrahim; Miravitlles, Marc; Migliori, Giovanni Battista

doi:10.1183/13993003.01356-2016

Cited by 34 publications

(48 citation statements)

References 57 publications

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“…Likewise, the potent activity of clofazimine evident in combination therapy indicates that this context may be more appropriate for evaluating dose-ranging effects of the drug. Importantly, as monotherapy with any drug is never used for the treatment of active TB (1,2,27), preclinical assessment of clofazimine's activity within a multidrug regimen may provide data more relevant and informative for clinical translation.…”

Section: Discussionmentioning

confidence: 99%

“…T he treatment of drug-susceptible tuberculosis (TB) requires the administration of multiple drugs for at least 6 months, and the programmatic management of TB requires daily supervision of treatment to ensure regular drug intake (1,2). In addition to the incredible burden that 6 months of directly observed therapy places on patients, the substantial public health resources and infrastructure required to ensure successful treatment are an enormous burden on TB control programs (3,4).…”

mentioning

confidence: 99%

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Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis

Ammerman

Swanson

Bautista

et al. 2018

Antimicrob Agents Chemother

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The antileprosy drug clofazimine was recently repurposed as part of a newly endorsed short-course regimen for multidrug-resistant tuberculosis. It also enables significant treatment shortening when added to the first-line regimen for drug-susceptible tuberculosis in a mouse model. However, clofazimine causes dose- and duration-dependent skin discoloration in patients, and the optimal clofazimine dosing strategy in the context of the first-line regimen is unknown. We utilized a well-established mouse model to systematically address the impacts of duration, dose, and companion drugs on the treatment-shortening activity of clofazimine in the first-line regimen. In all studies, the primary outcome was relapse-free cure (culture-negative lungs) 6 months after stopping treatment, and the secondary outcome was bactericidal activity, i.e., the decline in the lung bacterial burden during treatment. Our findings indicate that clofazimine activity is most potent when coadministered with first-line drugs continuously throughout treatment and that equivalent treatment-shortening results are obtained with half the dose commonly used in mice. However, our studies also suggest that clofazimine at low exposures may have negative impacts on treatment outcomes, an effect that was evident only after the first 3 months of treatment. These data provide a sound evidence base to inform clofazimine dosing strategies to optimize the antituberculosis effect while minimizing skin discoloration. The results also underscore the importance of conducting long-term studies to allow the full evaluation of drugs administered in combination over long durations.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis

Ammerman

Swanson

Bautista

et al. 2018

Antimicrob Agents Chemother

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“…The first-line regimen for treatment of drug-susceptible TB consists of daily administration of four drugs (rifampin, isoniazid, pyrazinamide, and ethambutol) for at least two months, followed by an additional four months of daily rifampin and isoniazid (3, 4). In addition to the burden on individual patients, administration of a six-month, multidrug regimen requires significant resources from a public health perspective, especially if treatment is directly observed as is recommended (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Treatment-shortening effect of a novel regimen combining high-dose rifapentine and clofazimine in pathologically distinct mouse models of tuberculosis

Saini

Ammerman

Chang

et al. 2019

Preprint

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High-dose rifapentine and clofazimine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.

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“…The reduction of the linezolid dose from 600 to 300 mg·day −1 or 600 mg three times weekly is generally sufficient to manage them [19,57,58]. The possibility to use TDM (treatment drug monitoring) to adjust the dose and minimise adverse events has been recently recommended [59,60].…”

Section: Xdr-tbmentioning

confidence: 99%

Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases

et al. 2017

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The ERS-endorsed official ATS/CDC/IDSA clinical practice guidelines on treatment of drug-susceptible tuberculosis

Abstract: @ERSpublications Updated clinical practice guidelines on TB treatment provide clinical and public health management recommendations http://ow.ly/FDcN302Jdmp

Cited by 34 publications

References 57 publications

Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis

Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis

Treatment-shortening effect of a novel regimen combining high-dose rifapentine and clofazimine in pathologically distinct mouse models of tuberculosis

Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases

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