ABSTRACT
BACKGROUND: Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. METHODS/DESIGN: This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. DISCUSSION: Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Fever/drug therapy , Trimethoprim, Sulfamethoxazole Drug Combination/administration & dosage , Typhoid Fever/drug therapy , Typhus, Epidemic Louse-Borne/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , Child , Child, Preschool , Clinical Protocols , Double-Blind Method , Drug Resistance, Bacterial , Female , Fever/diagnosis , Fever/microbiology , Humans , Male , Middle Aged , Nepal , Research Design , Time Factors , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Typhoid Fever/diagnosis , Typhoid Fever/microbiology , Typhus, Epidemic Louse-Borne/diagnosis , Typhus, Epidemic Louse-Borne/microbiology , Young AdultABSTRACT
We report a case of a tubo-ovarian abscess infected with Salmonella enterica serotype typhi A 19-year-old Nepalese woman presented to a hospital in Kathmandu with lower abdominal pain, constipation, fever and a non-healing, suppurative surgical wound from an emergency caesarian section performed 2 months previously at 37 weeks of pregnancy. She also had an exploratory laparotomy for an appendix perforation with peritonitis at 25 weeks of gestation. Her wound infection did not respond to cloxacillin and she had an exploratory laparotomy, and a tubo-ovarian abscess was found from which S. typhi was isolated. She had a bilateral salpingo-oophorectomy and responded to 14 days of chloramphenicol. A tubo-ovarian abscess is a rare complication of enteric fever.
