Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.
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Authors
Karkey, Abhilasha
Dongol, Sabina
Arjyal, Amit
Veeraraghavan, Balaji
Dolecek, Christiane
Gajurel, Damodar
Phuong, Dung Nguyen Thi
Thanh, Duy Pham
Qamar, Farah
John, Jacob
Wolbers, Marcel
Sharifuzzaman, M
Maharjan, Nhukesh
Olliaro, Piero
Rupali, Priscilla
Shakoor, Sadia
Rijal, Samita
Qureshi, Sonia
Joshi, Subi
Ahmed, Tahmeed
Bao, Tran Nguyen
Publication Date
2021Journal Title
Wellcome Open Res
ISSN
2398-502X
Publisher
F1000 Research Ltd
Volume
6
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Giri, A., Karkey, A., Dongol, S., Arjyal, A., Maharjan, A., Veeraraghavan, B., Paudyal, B., et al. (2021). Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.. Wellcome Open Res, 6 https://doi.org/10.12688/wellcomeopenres.16801.2
Abstract
Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia. A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime, or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of clinically suspected and culture-confirmed typhoid fever in South Asia. Methods: This is a phase IV, international multi-center, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomized to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal, and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020).
Keywords
azithromycin, Rct, South Asia, Cefixime, Enteric Fever
Sponsorship
Medical Research Council (MR/T005033/1)
Identifiers
PMC8772527, 35097222
External DOI: https://doi.org/10.12688/wellcomeopenres.16801.2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334710
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