MAJOR ARTICLE 1958 • CID 2020:70 (1 May) • Malik et al Clinical Infectious Diseases Received 26 March 2019; editorial decision 31 May 2019; accepted 11 June 2019; published online June 12, 2019. a M. C. B. and H. H. contributed equally to this work. Correspondence: A. A. Malik, Global Health Directorate—Indus Health Network, 5th Floor, Woodcraft Building, Plot 3 & 3A Sector 47, Korangi Creek Road, Karachi, Pakistan (amyn. malik@ghd.ihn.org.pk). Clinical Infectious Diseases ® 2020;70(9):1958–65 © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciz502 Tuberculosis Preventive Terapy for Individuals Exposed to Drug-resistant Tuberculosis: Feasibility and Safety of a Community-based Delivery of Fluoroquinolone- containing Preventive Regimen Amyn A. Malik, 1,2,3, Junaid Fuad, 1 Sara Siddiqui, 1 Farhana Amanullah, 1,2 Maria Jaswal, 1 Zainab Barry, 1 Farhat Jabeen, 1 Razia Fatima, 4 Courtney M. Yuen, 5,6 Naseem Salahuddin, 1,7 Aamir J. Khan, 1,2 Salmaan Keshavjee, 5,6,8 Mercedes C. Becerra, 5,6,8,a and Hamidah Hussain 2,a 1 Global Health Directorate, Indus Health Network, Karachi, Pakistan; 2 Interactive Research and Development Global, Singapore; 3 Emory University Rollins School of Public Health, Atlanta, Georgia; 4 National TB Control Program, Pakistan; 5 Department of Global Health and Social Medicine, Harvard Medical School, and 6 Division of Global Health Equity, Brigham and Women’s Hospital, Boston, Massachusetts; 7 Indus Hospital, Karachi, Pakistan; and 8 Partners In Health, Boston, Massachusetts Background. Observational studies have demonstrated the efectiveness of a fuoroquinolone-based regimen to treat individuals presumed to be infected with drug-resistant tuberculosis (DR-TB). We sought to assess the feasibility of this approach in an urban setting in South Asia. Methods. From February 2016 until March 2017, all household contacts of DR-TB patients enrolled at the Indus Hospital were screened for TB symptoms at home. Children aged 0–17 years, symptomatic adults, and those with an immunocompromising condi- tion (human immunodefciency virus, diabetes, or malnutrition) were evaluated for TB disease. Contacts diagnosed with TB disease were started on treatment. Contacts without TB disease aged <5 years, contacts aged between 5 and 17 years with either a positive tuberculin skin test or an immunocompromising condition, or contacts aged ≥18 years with an immunocompromising condition were ofered 6 months of treatment with a fuoroquinolone. Results. One hundred households with 800 contacts were enrolled: 353 (44.1%) individuals aged ≤17 years with a median age of 19 years (interquartile range, 10–32); 423 (52.9%) were males. In total, 737 (92.1%) individuals were screened, of which 8 were already on treatment for TB (1.1%); another 3 (0.4%) contacts were diagnosed with TB disease and started on treatment. Of 215 eligible for infection treatment, 172 (80.0%) contacts initiated and 121 (70.3%) completed treatment. No TB disease or signifcant adverse events were observed during 12 months of follow-up. Conclusions. Fluoroquinolone-based treatment for contacts with presumed DR-TB infection is feasible and well tolerated in a high TB burden setting. Keywords. drug-resistant tuberculosis infection; preventive therapy; fuoroquinolone; household contacts. In 2017, tuberculosis (TB) killed 1.3 million people worldwide, making it the biggest infectious killer of adults and the leading cause of death for people living with human immunodeficiency virus (HIV) [1]. Almost 558 000 cases of TB out of 10 million new cases were due to drug-resistant TB (DR-TB), making this disease one of the highest contributors to the burden of global antimicrobial resistance [1, 2]. Most DR-TB disease results from infection with drug-resistant strains of Mycobacterium tuber- culosis rather than drug resistance acquired during treatment [3–5]. Among household contacts of those sick with DR-TB, 47.2% (95% confidence interval, 30.0%–61.4%) are infected [6]. Of persons infected with TB, 10%–20% develop TB disease [7]. In children aged <5 years who are exposed at home to DR-TB, 6% to 24% become sick [8, 9]. The current global cure rate for people with disease caused by DR-TB is 55% [1]. Preventing the progression of TB infection to disease is a fundamental part of a comprehensive epidemic control strategy for TB elimination [10, 11] and the cornerstone of the Zero TB Initiative, a strategy aimed at TB elimination [12, 13]. As with drug-susceptible TB, this is achieved for those infected with strains of DR-TB by screening and treating close contacts of patients with DR-TB for disease and infection [14, 15]. Such an approach has been used to successfully stop ongoing trans- mission of DR-TB in the Federated States of Micronesia, the United States, the United Kingdom, and South Africa, with high efectiveness and low toxicity [8, 16–19]. While no clinical trials have evaluated regimens specifcally for presumed DR-TB