• George M Varghese, Divya Dayanand, Karthik Gunasekaran, Debasree Kundu, Mukta Wyawahare, Navneet Sharma, Dhruva Chaudhry, Sanjay K Mahajan, Kavitha Saravu, Blessed W Aruldhas, Binu S Mathew, Roshini G Nair, Nalini Newbigging, Aswathy Mathew, Kundavaram P P Abhilash, Manisha Biswal, Ann H Prasad, Anand Zachariah, Ramya Iyadurai, Samuel G Hansdak, Sowmya Sathyendra, Thambu D Sudarsanam, John A J Prakash, Abi Manesh, Alladi Mohan, Joel Tarning, Stuart D Blacksell, Pimnara Peerawaranun, Naomi Waithira, Mavuto Mukaka, Phaik Yeong Cheah, John V Peter, Ooriapadickal C Abraham, DayNicholas P JNPJFrom the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microb, and INTREST Trial Investigators.
• From the Departments of Infectious Diseases (G.M.V., D.D., D.K., R.G.N., A.H.P., A. Manesh), Medicine (K.G., N.N., A.Z., R.I., S.G.H., S.S., T.D.S., O.C.A.), Pharmacology (B.W.A., B.S.M., A. Mathew), Emergency Medicine (K.P.P.A.), Microbiology (J.A.J.P.), and Critical Care (J.V.P.), Christian Medical College, Vellore, the Department of Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Pondicherry (M.W.), the Departments of Internal Medicine (N.S.) and Microbiology (M.B.), Post Graduate Institute of Medical Education and Research, Chandigarh, the Department of Pulmonary Care and Critical Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak (D.C.), the Department of Medicine, Indira Gandhi Medical College, Shimla (S.K.M.), the Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal (K.S.), and the Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati (A. Mohan) - all in India; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (J.T., S.D.B., P.P., N.W., M.M., P.Y.C., N.P.J.D.); and the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom (J.T., S.D.B., N.W., M.M., P.Y.C., N.P.J.D.).
• N. Engl. J. Med. 2023 Mar 2; 388 (9): 792803792-803.

BackgroundThe appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.MethodsIn this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5.ResultsAmong 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups.ConclusionsCombination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).Copyright © 2023 Massachusetts Medical Society.

22 keywords...

hide…