Newton, PN;
Keolouangkhot, V;
Lee, SJ;
Choumlivong, K;
Sisouphone, S;
Choumlivong, K;
Vongsouvath, M;
Mayxay, M;
Chansamouth, V;
Davong, V;
et al.
Newton, PN; Keolouangkhot, V; Lee, SJ; Choumlivong, K; Sisouphone, S; Choumlivong, K; Vongsouvath, M; Mayxay, M; Chansamouth, V; Davong, V; Phommasone, K; Sirisouk, J; Blacksell, SD; Nawtaisong, P; Moore, CE; Castonguay-Vanier, J; Dittrich, S; Rattanavong, S; Chang, K; Darasavath, C; Rattanavong, O; Paris, DH; Phetsouvanh, R
(2019)
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus.
Clin Infect Dis, 68 (5).
pp. 738-747.
ISSN 1537-6591
https://doi.org/10.1093/cid/ciy563
SGUL Authors: Moore, Catrin Elisabeth
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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.
Item Type: | Article | ||||||||
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Additional Information: | © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | ||||||||
Keywords: | Rickettsia typhi, Laos, azithromycin, doxycycline, murine typhus, Adult, Anti-Bacterial Agents, Azithromycin, Doxycycline, Female, Humans, Laos, Male, Neglected Diseases, Prospective Studies, Typhus, Endemic Flea-Borne, Young Adult, Humans, Typhus, Endemic Flea-Borne, Azithromycin, Doxycycline, Anti-Bacterial Agents, Prospective Studies, Adult, Laos, Female, Male, Young Adult, Neglected Diseases, murine typhus, Rickettsia typhi, Laos, doxycycline, azithromycin, 06 Biological Sciences, 11 Medical and Health Sciences, Microbiology | ||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||
Journal or Publication Title: | Clin Infect Dis | ||||||||
ISSN: | 1537-6591 | ||||||||
Language: | eng | ||||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||||
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PubMed ID: | 30020447 | ||||||||
Web of Science ID: | WOS:000459671900009 | ||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/114464 | ||||||||
Publisher's version: | https://doi.org/10.1093/cid/ciy563 |
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