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Title: A prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus
Authors: Paul N. Newton
Valy Keolouangkhot
Sue J. Lee
Khamla Choumlivong
Siho Sisouphone
Khamloune Choumlivong
Manivanh Vongsouvath
Mayfong Mayxay
Vilada Chansamouth
Viengmon Davong
Koukeo Phommasone
Joy Sirisouk
Stuart D. Blacksell
Pruksa Nawtaisong
Catrin E. Moore
Josée Castonguay-Vanier
Sabine Dittrich
Sayaphet Rattanavong
Ko Chang
Chirapha Darasavath
Oudayvone Rattanavong
Daniel H. Paris
Rattanaphone Phetsouvanh
University of Oxford
Universitat Basel
Swiss Tropical and Public Health Institute (Swiss TPH)
Mahidol University
Setthathirat Hospital
Mahosot Hospital
University of Health Sciences
Keywords: Medicine
Issue Date: 15-Feb-2019
Citation: Clinical Infectious Diseases. Vol.68, No.5 (2019), 738-747
Abstract: © The Author(s) 2018. Background Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy. Methods A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse. Results Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)-confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P <.001). Among R. typhi PCR-positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P =.005) and D7 (1.5- and 1.6-fold higher; P =.02). No patients returned with PCR-confirmed R. typhi relapse. Conclusion In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.
ISSN: 15376591
Appears in Collections:Scopus 2019

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