Open AccessAzithromycin 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
Author(s) -
Abhishek Giri,
Abhilasha Karkey,
Sabina Dongol,
Amit Arjyal,
Anjana Maharjan,
Balaji Veeraraghavan,
Buddhi Paudyal,
Christiane Dolecek,
Damodar Gajurel,
Phuong Dnt.,
Duy Pham Thanh,
Farah Naz Qamar,
Gagandeep Kang,
H Van Hien,
Jacob John,
Katrina Lawson,
Marcel Wolbers,
Ho Van Hien,
Mohammad Sharifuzzaman,
Nantasit Luangasanatip,
Nhukesh Maharjan,
Piero Olliaro,
Priscilla Rupali,
Ronas Shakya,
Sadia Shakoor,
Suraj Rijal,
Sonia Qureshi,
Stephen Baker,
Suchita Joshi,
Tahmeed Ahmed,
Thomas C. Darton,
Tran Nguyen Bao,
Yoel Lubell,
E Kesteyln,
Guy Thwaites,
Christopher M. Parry,
Buddha Basnyat
Publication year - 2021
Publication title -
wellcome open research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.298
H-Index - 21
ISSN - 2398-502X
DOI - 10.12688/wellcomeopenres.16801.2
Subject(s) - cefixime , azithromycin , medicine , typhoid fever , antibiotics , virology , cephalosporin , biology , microbiology and biotechnology
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)