• Greg J Fox, Nguyen Viet Nhung, Nguyen Cam Binh, Nguyen Binh Hoa, Frances L Garden, Andrea Benedetti, Pham Ngoc Yen, Nguyen Kim Cuong, Emily L MacLean, H Manisha Yapa, David W Dowdy, Nguyen Huu Lan, Elyse Guevara-Rattray, Pham Duc Cuong, Ori Solomon, Marcel A Behr, Ben J Marais, Steven M Graham, Dick Menzies, Thu AnhNguyenNFrom the Faculty of Medicine and Health (G.J.F., P.N.Y., E.L.M., H.M.Y., E.G.-R., P.D.C., B.J.M., N.T.A.), the Sydney Infectious Diseases Institute (B.J.M.), and Sydney Medical School (H.M.Y.), University of Sydney, and Royal Prince Alfred H, and Guy B Marks.
• From the Faculty of Medicine and Health (G.J.F., P.N.Y., E.L.M., H.M.Y., E.G.-R., P.D.C., B.J.M., N.T.A.), the Sydney Infectious Diseases Institute (B.J.M.), and Sydney Medical School (H.M.Y.), University of Sydney, and Royal Prince Alfred Hospital, Sydney Local Health District (G.J.F.), Camperdown, NSW, the Woolcock Institute of Medical Research, Macquarie Park, NSW (G.J.F., N.C.B., P.N.Y., P.D.C., N.T.A., G.B.M.), the School of Clinical Medicine, University of New South Wales, Liverpool (F.L.G.), and the Department of Paediatrics, University of Melbourne (S.M.G.), and the Division of Global Health, Burnet Institute (G.B.M.), Melbourne, VIC - all in Australia; the University of Medicine and Pharmacy, Vietnam National University (N.V.N.), and the National Lung Hospital, Ba Dinh District (N.B.H., N.K.C.), Hanoi, and Pham Ngoc Thach Hospital, Ho Chi Minh City (N.H.L.) - all in Vietnam; the Departments of Medicine (A.B., O.S., M.A.B., D.M.), Epidemiology, Biostatistics, and Occupational Health (A.B., M.A.B., D.M.), and Microbiology and Immunology (O.S., M.A.B.), McGill University, Montreal; and Johns Hopkins University, Baltimore (D.W.D.).
• N. Engl. J. Med. 2024 Dec 19; 391 (24): 230423142304-2314.

BackgroundPrevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating Mycobacterium tuberculosis infection among contacts of persons with drug-resistant tuberculosis are lacking.MethodsWe conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat M. tuberculosis infection. The trial population comprised household contacts of persons with bacteriologically confirmed rifampicin-resistant or multidrug-resistant (MDR) tuberculosis in Vietnam. Contacts of any age with a positive tuberculin skin test or immunologic impairment were eligible. The primary end point was bacteriologically confirmed tuberculosis within 30 months. Secondary end points included grade 3 or 4 adverse events, death from any cause, and acquired drug resistance.ResultsOf 3948 persons screened for eligibility, 61 (1.5%) had coprevalent tuberculosis (defined as active tuberculosis disease diagnosed before randomization) and 2041 underwent randomization. Of these 2041 participants, 1995 (97.7%) completed 30 months of follow-up, had a primary end-point event, or died. Confirmed tuberculosis occurred in 6 participants (0.6%) in the levofloxacin group and 11 (1.1%) in the placebo group (incidence rate ratio, 0.55; 95% confidence interval [CI], 0.19 to 1.62); this difference was not significant. There was little difference in grade 3 or 4 adverse events between the two groups (risk difference, 1.0 percentage point; 95% CI, -0.3 to 2.4). Adverse events of any grade were reported in 306 participants (31.9%) taking levofloxacin and 125 (13.0%) taking placebo (risk difference, 18.9 percentage points; 95% CI, 14.2 to 23.6). No acquired fluoroquinolone resistance was observed.ConclusionsAlthough the incidence of tuberculosis was lower in the levofloxacin group than in the placebo group at 30 months, the difference was not significant. (Funded by the National Health and Medical Research Council of Australia; VQUIN MDR Australia New Zealand Clinical Trials Registry number, ACTRN12616000215426.).Copyright © 2024 Massachusetts Medical Society.

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