A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus. (18th July 2018)

• Record Type: Journal Article
• Authors: Newton, Paul N; Keolouangkhot, Valy; Lee, Sue J; Choumlivong, Khamla; Sisouphone, Siho; Choumlivong, Khamloune; Vongsouvath, Manivanh; Mayxay, Mayfong; Chansamouth, Vilada; Davong, Viengmon; Phommasone, Koukeo; Sirisouk, Joy; Blacksell, Stuart D; Nawtaisong, Pruksa; Moore, Catrin E; Castonguay-Vanier, Josée; Dittrich, Sabine; Rattanavong, Sayaphet; Chang, Ko; Darasavath, Chirapha; Rattanavong, Oudayvone; Paris, Daniel H; Phetsouvanh, Rattanaphone
• Is Part Of: Clinical infectious diseases. Volume 68:Number 5(2019)
• Page Start: 738
• Page End: 747
• Publication Date: 2018-07-18
• Subjects: murine typhus -- Rickettsia typhi -- Laos -- doxycycline -- azithromycin; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy563
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: 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. Clinical Trial Registration: ISRCTN47812566. Abstract : A clinical trial of murine typhus, or infection with Rickettsia typhi, in Lao adults suggests that azithromycin is inferior to doxycycline for the oral therapy of uncomplicated murine typhus. Three and 7 days of doxycycline have similar efficacy.