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

Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults children presenting to health care facilities low resource settings such as the South Asia. A 7-day course single oral antimicrobial ciprofloxacin, cefixime, or azithromycin commonly used for its treatment. Increasing resistance threatens effectiveness these treatment choices. We hypothesize that combined with (active mainly intracellularly) cefixime extracellularly) will be better option clinically suspected culture-confirmed typhoid Asia. Methods: This phase IV, international multi-center, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients uncomplicated randomized one two interventions: Arm A: 20mg/kg/day dose once daily (maximum 1gm/day) divided doses 400mg bd) 7 days, B: (max days AND cefixime-matched placebo days. recruit 1500 patients across sites Bangladesh, India, Nepal, Pakistan. assess whether outcomes are combination after week at one- three-months follow-up. Discussion: Combined may limit emergence if components active against resistant sub-populations not covered by other activity. If than treatment, this an important result Asia endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020)