R R Kempker1, L Mikiashvili2, Y Zhao3, D Benkeser3, K Barbakadze2, N Bablishvili2, Z Avaliani2, C A Peloquin4, H M Blumberg1,5, M Kipiani2. 1. Department of Medicine, Division of Infectious Disease, Emory University School of Medicine, Atlanta, Georgia, USA. 2. National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia. 3. Department of Biostatistics and Bioinformatics, Emory Rollins School of Public Health, Atlanta, Georgia, USA. 4. Department of Pharmacy, University of Florida, Gainesville, Florida, USA. 5. Departments of Epidemiology and Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
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.
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.
Authors: Nafees Ahmad; Shama D Ahuja; Onno W Akkerman; Jan-Willem C Alffenaar; Laura F Anderson; Parvaneh Baghaei; Didi Bang; Pennan M Barry; Mayara L Bastos; Digamber Behera; Andrea Benedetti; Gregory P Bisson; Martin J Boeree; Maryline Bonnet; Sarah K Brode; James C M Brust; Ying Cai; Eric Caumes; J Peter Cegielski; Rosella Centis; Pei-Chun Chan; Edward D Chan; Kwok-Chiu Chang; Macarthur Charles; Andra Cirule; Margareth Pretti Dalcolmo; Lia D'Ambrosio; Gerard de Vries; Keertan Dheda; Aliasgar Esmail; Jennifer Flood; Gregory J Fox; Mathilde Fréchet-Jachym; Geisa Fregona; Regina Gayoso; Medea Gegia; Maria Tarcela Gler; Sue Gu; Lorenzo Guglielmetti; Timothy H Holtz; Jennifer Hughes; Petros Isaakidis; Leah Jarlsberg; Russell R Kempker; Salmaan Keshavjee; Faiz Ahmad Khan; Maia Kipiani; Serena P Koenig; Won-Jung Koh; Afranio Kritski; Liga Kuksa; Charlotte L Kvasnovsky; Nakwon Kwak; Zhiyi Lan; Christoph Lange; Rafael Laniado-Laborín; Myungsun Lee; Vaira Leimane; Chi-Chiu Leung; Eric Chung-Ching Leung; Pei Zhi Li; Phil Lowenthal; Ethel L Maciel; Suzanne M Marks; Sundari Mase; Lawrence Mbuagbaw; Giovanni B Migliori; Vladimir Milanov; Ann C Miller; Carole D Mitnick; Chawangwa Modongo; Erika Mohr; Ignacio Monedero; Payam Nahid; Norbert Ndjeka; Max R O'Donnell; Nesri Padayatchi; Domingo Palmero; Jean William Pape; Laura J Podewils; Ian Reynolds; Vija Riekstina; Jérôme Robert; Maria Rodriguez; Barbara Seaworth; Kwonjune J Seung; Kathryn Schnippel; Tae Sun Shim; Rupak Singla; Sarah E Smith; Giovanni Sotgiu; Ganzaya Sukhbaatar; Payam Tabarsi; Simon Tiberi; Anete Trajman; Lisa Trieu; Zarir F Udwadia; Tjip S van der Werf; Nicolas Veziris; Piret Viiklepp; Stalz Charles Vilbrun; Kathleen Walsh; Janice Westenhouse; Wing-Wai Yew; Jae-Joon Yim; Nicola M Zetola; Matteo Zignol; Dick Menzies Journal: Lancet Date: 2018-09-08 Impact factor: 79.321
Authors: Thi Van Anh Nguyen; Richard M Anthony; Anne-Laure Bañuls; Thi Van Anh Nguyen; Dinh Hoa Vu; Jan-Willem C Alffenaar Journal: Clin Infect Dis Date: 2018-05-02 Impact factor: 9.079
Authors: V Cox; G Brigden; R H Crespo; E Lessem; S Lynch; M L Rich; B Waning; J Furin Journal: Int J Tuberc Lung Dis Date: 2018-04-01 Impact factor: 2.373
Authors: L Guglielmetti; C Hewison; Z Avaliani; J Hughes; N Kiria; N Lomtadze; N Ndjeka; S Setkina; A Shabangu; W Sikhondze; A Skrahina; N Veziris; J Furin Journal: Int J Tuberc Lung Dis Date: 2017-02-01 Impact factor: 2.373
Authors: Maria Tarcela Gler; Vija Skripconoka; Epifanio Sanchez-Garavito; Heping Xiao; Jose L Cabrera-Rivero; Dante E Vargas-Vasquez; Mengqiu Gao; Mohamed Awad; Seung-Kyu Park; Tae Sun Shim; Gee Young Suh; Manfred Danilovits; Hideo Ogata; Anu Kurve; Joon Chang; Katsuhiro Suzuki; Thelma Tupasi; Won-Jung Koh; Barbara Seaworth; Lawrence J Geiter; Charles D Wells Journal: N Engl J Med Date: 2012-06-07 Impact factor: 91.245
Authors: Salim Allana; Elena Shashkina; Barun Mathema; Nino Bablishvili; Nestani Tukvadze; N Sarita Shah; Russell R Kempker; Henry M Blumberg; Pravi Moodley; Koleka Mlisana; James C M Brust; Neel R Gandhi Journal: Emerg Infect Dis Date: 2017-03 Impact factor: 6.883
Authors: Daniel S Graciaa; Maia Kipiani; Matthew J Magee; Lali Mikiashvili; Ketevan Barbakadze; Nino Bablishvili; Sara C Auld; Wael A Alghamdi; Mohammad H Alshaer; Charles A Peloquin; Zaza Avaliani; Henry M Blumberg; Russell R Kempker Journal: Antimicrob Agents Chemother Date: 2022-08-02 Impact factor: 5.938
Authors: Emily E Evans; Teona Avaliani; Mariam Gujabidze; Tinatin Bakuradze; Maia Kipiani; Shorena Sabanadze; Alison G C Smith; Zaza Avaliani; Jeffrey M Collins; Russell R Kempker Journal: PLoS One Date: 2022-06-24 Impact factor: 3.752
Authors: Russell R Kempker; Alison G C Smith; Teona Avaliani; Mariam Gujabidze; Tinatin Bakuradze; Shorena Sabanadze; Zaza Avaliani; Jeffrey M Collins; Henry M Blumberg; Mohammad H Alshaer; Charles A Peloquin; Maia Kipiani Journal: Clin Infect Dis Date: 2022-09-10 Impact factor: 20.999
Authors: Wael A Alghamdi; Mohammad H Al-Shaer; Guohua An; Abdullah Alsultan; Maia Kipiani; Ketevan Barbakadze; Lali Mikiashvili; David Ashkin; David E Griffith; J Peter Cegielski; Russell R Kempker; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2020-09-21 Impact factor: 5.191
Authors: Wael A Alghamdi; Mohammad H Al-Shaer; Maia Kipiani; Ketevan Barbakadze; Lali Mikiashvili; Russell R Kempker; Charles A Peloquin Journal: J Antimicrob Chemother Date: 2021-03-12 Impact factor: 5.790
Authors: James C M Brust; Neel R Gandhi; Sean Wasserman; Gary Maartens; Shaheed V Omar; Nazir A Ismail; Angela Campbell; Lindsay Joseph; Alexandria Hahn; Salim Allana; Alfonso C Hernandez-Romieu; Chenshu Zhang; Koleka Mlisana; Charle A Viljoen; Benjamin Zalta; Ismaeel Ebrahim; Meghan Franczek; Iqbal Master; Limpho Ramangoaela; Julian Te Riele; Graeme Meintjes Journal: Clin Infect Dis Date: 2021-12-06 Impact factor: 9.079
Authors: Giorgi Kuchukhidze; Davit Baliashvili; Natalia Adamashvili; Ana Kasradze; Russell R Kempker; Matthew J Magee Journal: Open Forum Infect Dis Date: 2021-03-15 Impact factor: 3.835