Journal Article > CommentaryFull Text
Am J Respir Crit Care Med. 2017 July 17; Volume 196 (Issue 11); DOI:10.1164/rccm.201705-0988LE
Varaine FFV, Guglielmetti L, Mitnick CD
Am J Respir Crit Care Med. 2017 July 17; Volume 196 (Issue 11); DOI:10.1164/rccm.201705-0988LE
Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Bastard M, Bonnet MMB, du Cros PAK, Khamraev AK, Hayrapetyan A, et al.
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2016 October 15; Volume 194 (Issue 8); 1028-1029.; DOI:10.1164/rccm.201605-1080LE
Varaine FFV, Guglielmetti L, Huerga H, Bonnet MMB, Kiria N, et al.
Am J Respir Crit Care Med. 2016 October 15; Volume 194 (Issue 8); 1028-1029.; DOI:10.1164/rccm.201605-1080LE
Journal Article > ResearchFull Text
Am J Respir Crit Care Med. 2007 December 7; Volume 175 (Issue 5); DOI:10.1164/rccm.200610-1439OC
Rangaka MX, Wilkinson KA, Seldon R, van Cutsem G, Meintjes GA, et al.
Am J Respir Crit Care Med. 2007 December 7; Volume 175 (Issue 5); DOI:10.1164/rccm.200610-1439OC
RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.
Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2018 July 3; Volume 198 (Issue 9); DOI:10.1164/rccm.201801-0019LE
Bastard M, Guglielmetti L, Huerga H, Hayrapetyan A, Khachatryan N, et al.
Am J Respir Crit Care Med. 2018 July 3; Volume 198 (Issue 9); DOI:10.1164/rccm.201801-0019LE
Journal Article > CommentaryAbstract
Am J Respir Crit Care Med. 2017 December 1; Volume 196 (Issue 11); DOI:10.1164/rccm.201705-0988LE
Varaine FFV, Guglielmetti L, Mitnick CD
Am J Respir Crit Care Med. 2017 December 1; Volume 196 (Issue 11); DOI:10.1164/rccm.201705-0988LE
Journal Article > ResearchFull Text
Effectiveness of bedaquiline use beyond six months in patients with multidrug-resistant tuberculosis
Am J Respir Crit Care Med. 2023 June 1; Volume 207 (Issue 11); 1525-1532.; DOI:10.1164/rccm.202211-2125OC
Trevisi L, Hernán MA, Mitnick CD, Khan UT, Seung KJ, et al.
Am J Respir Crit Care Med. 2023 June 1; Volume 207 (Issue 11); 1525-1532.; DOI:10.1164/rccm.202211-2125OC
RATIONALE
Current recommendations for the treatment of rifampin- and multidrug-resistant tuberculosis include bedaquiline used for six months or longer. Evidence is needed to inform the optimal duration of bedaquiline.
OBJECTIVES
We emulated a target trial to estimate the effect of three bedaquiline duration treatment strategies (6 months, 7-11 months, ≥ 12 months) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis.
METHODS
To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse-probability weighting.
MAIN RESULTS
The 1,468 eligible individuals received a median of four (IQR: 4-5) likely effective drugs. In 87.1% and 77.7%, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment (95% CI) was 0.85 (0.81, 0.88) for 6 months of BDQ, 0.77 (0.73, 0.81) for 7-11 months, and 0.86 (0.83, 0.88) for > 12 months. Compared with 6 months of bedaquiline, the ratio of treatment success (95% CI) was 0.91 (0.85, 0.96) for 7-11 months and 1.01 (0.96, 1.06) for > 12 months. Analyses that did not account for immortal time bias found a higher probability of successful treatment with > 12 months: ratio 1.09 (1.05, 1.14).
CONCLUSIONS
Bedaquiline use beyond six months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time can bias estimate of effects of treatment duration. Future analyses should explore the effect of duration of bedaquiline and other drugs in subgroups with advanced disease and/or receiving less potent regimens.
Current recommendations for the treatment of rifampin- and multidrug-resistant tuberculosis include bedaquiline used for six months or longer. Evidence is needed to inform the optimal duration of bedaquiline.
OBJECTIVES
We emulated a target trial to estimate the effect of three bedaquiline duration treatment strategies (6 months, 7-11 months, ≥ 12 months) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis.
METHODS
To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse-probability weighting.
MAIN RESULTS
The 1,468 eligible individuals received a median of four (IQR: 4-5) likely effective drugs. In 87.1% and 77.7%, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment (95% CI) was 0.85 (0.81, 0.88) for 6 months of BDQ, 0.77 (0.73, 0.81) for 7-11 months, and 0.86 (0.83, 0.88) for > 12 months. Compared with 6 months of bedaquiline, the ratio of treatment success (95% CI) was 0.91 (0.85, 0.96) for 7-11 months and 1.01 (0.96, 1.06) for > 12 months. Analyses that did not account for immortal time bias found a higher probability of successful treatment with > 12 months: ratio 1.09 (1.05, 1.14).
CONCLUSIONS
Bedaquiline use beyond six months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time can bias estimate of effects of treatment duration. Future analyses should explore the effect of duration of bedaquiline and other drugs in subgroups with advanced disease and/or receiving less potent regimens.
Journal Article > ReviewFull Text
Am J Respir Crit Care Med. 2016 November 17; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
Harausz EP, Garcia-Prats AJ, Seddon JA, Schaaf HS, Hesseling AC, et al.
Am J Respir Crit Care Med. 2016 November 17; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.
Journal Article > ResearchFull Text
Am J Respir Crit Care Med. 2020 July 24; Volume 203 (Issue 1); 111-119.; DOI:10.1164/rccm.202001-0135OC
Franke MF, Khan PY, Hewison CCH, Khan UT, Huerga H, et al.
Am J Respir Crit Care Med. 2020 July 24; Volume 203 (Issue 1); 111-119.; DOI:10.1164/rccm.202001-0135OC
BACKGROUND
Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion.
METHODS
We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.
FINDINGS
1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.
INTERPRETATION
Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid- and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion.
METHODS
We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.
FINDINGS
1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0·73 [95% CI: 0·62, 0·84]) than patients without HIV (0·84 [95% CI: 0·79, 0·90]; p=0·03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0·68 [95% CI: 0·57, 0·79]) relative to patients without either (0·89; 95% CI: 0·84, 0·95; p=0·0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.
INTERPRETATION
Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.
Journal Article > CommentaryFull Text
Am J Respir Crit Care Med. 2023 January 30; Online ahead of print; DOI:10.1164/rccm.202211-2174CP
Mekontso Dessap A, Richard JCM, Baker T, Godard A, Carteaux G
Am J Respir Crit Care Med. 2023 January 30; Online ahead of print; DOI:10.1164/rccm.202211-2174CP