Bhutta 1994.

Study characteristics
Methods	Trial design: randomized Time period/duration of trial: June 1991‐May 1992 Duration of follow‐up: 12 weeks after cessation of therapy
Participants	Setting: hospital paediatric services Location: Karachi, Pakistan Age: children 6 months‐13 years of age. Mean age (+/‐ SD) was 8.4 (+/‐ 3.1) in ceftriaxone group, 6.6 (+/‐ 3.5) in cefixime group Gender: male = 31, female = 19 Health status of participants: not recorded Inclusion criteria: suspected MDR‐typhoid, with clinical features suggestive of typhoid and no response to treatment with oral chloramphenicol, amoxicillin or co‐trimoxazole for at least 7 days and/or history of close contact with an MDR‐culture‐positive case Exclusion criteria: vomiting, abdominal distension, ileus, or preceding ceftriaxone or cefixime therapy in the preceding week
Interventions	Ceftriaxone: IV, 60 mg/kg/day once daily for 14 days Cefixime: oral, 5 mg/kg/day twice daily for 14 days
Outcomes	Treatment failure: persistent pyrexia (≥ 38.5 °C for ≥ 24 h) and toxicity after 10 days of therapy Time to fever clearance (defervescence): temperature of ≤ 37.5 °C after 48 h of therapy Relapse: recurrence of clinical features of illness and a positive blood culture within 8 weeks of cessation of therapy Microbiological failure: not strictly defined, but mentioned as an outcome Typhoid morbidity score: defined as 0‐2 on the basis of fever, sensorium, hepatomegaly, presence of diarrhoea and vomiting, abdominal pain, abdominal examination Times to loss of irritability, abdominal pain, regression of splenomegaly Adverse events: monitored during the course of therapy ‐ clinical and laboratory values (not specified)
Organism type and antimicrobial susceptibility	S typhi only. 50/59 children had MDR‐typhoid following susceptibility testing.
Notes	80 children with suspected MDR admitted; typhoid confirmed on blood/bone marrow cultures in 59 cases, 9 of which were fully susceptible. Only MDR cases completed protocol and included in outcome analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details on randomization process given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No details given
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants followed up as per protocol
Selective reporting (reporting bias)	Low risk	Data reported for all stipulated outcome measures
Other bias	Low risk	No other obvious reasons for bias identified