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A prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus

Newton, Paul N. and Keolouangkhot, Valy and Lee, Sue J. and Choumlivong, Khamla and Sisouphone, Siho and Choumlivong, Khamloune and Vongsouvath, Manivanh and Mayxay, Mayfong and Chansamouth, Vilada and Davong, Viengmon and Phommasone, Koukeo and Sirisouk, Joy and Blacksell, Stuart D. and Nawtaisong, Pruksa and Moore, Catrin E. and Castonguay-Vanier, Josée and Dittrich, Sabine and Rattanavong, Sayaphet and Chang, Ko and Darasavath, Chirapha and Rattanavong, Oudayvone and Paris, Daniel H. and Phetsouvanh, Rattanaphone. (2019) A prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus. Clinical Infectious Diseases, 68 (5). pp. 738-747.

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Official URL: https://edoc.unibas.ch/69662/

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Abstract

Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.; 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.; 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.; 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.; ISRCTN47812566.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medicine (MED)
UniBasel Contributors:Paris, Daniel Henry
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:1058-4838
e-ISSN:1537-6591
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:06 Mar 2019 08:17
Deposited On:06 Mar 2019 08:17

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