COMPARISON OF SINGLE VERSUS COMBINATION DRUG THERAPY IN EXTENSIVELY DRUG RESISTANT SALMONELLA TYPHI IN TERMS OF TIME TO DEFERVESCENCE

Typhoid fever caused by Salmonella enterica serovar Typhi remains a major public health challenge in low- and middle-income countries. The emergence of extensively drug-resistant (XDR) strains, resistant to first-line agents, fluoroquinolones, and third-generation cephalosporins, has severely limited treatment options. In Pakistan, outbreaks of XDR typhoid have been reported since 2016, with thousands of confirmed cases in Karachi and Hyderabad. Current guidelines recommend carbapenems and azithromycin as the remaining effective agents, but the optimal regimen remains uncertain.

This randomized controlled trial will compare single-drug therapy (meropenem) with combination therapy (meropenem plus azithromycin) in pediatric patients aged 2-16 years with culture-confirmed XDR typhoid fever admitted to the Children's Hospital, Lahore. Ninety-four patients will be enrolled and randomly assigned to either treatment group using concealed allocation. Meropenem will be administered intravenously at 30 mg/kg/dose every 8 hours(maximum 2g per dose)while azithromycin will be given orally at 20 mg/kg/day according to hospital protocol. The primary endpoint is time to defervescence, defined as sustained resolution of fever for more than 48 hours. Secondary endpoints include duration of hospital stay and complication rates.

• Inclusion Criteria

• Children aged 2-16 years
• Culture-confirmed XDR typhoid fever (resistant to first-line agents, fluoroquinolones, and third-generation cephalosporins)
• Admitted to Children's Hospital & Institute of Child Health, Lahore

Informed consent obtained from parent/guardian

Exclusion criteria

• Age <2 years or >16 years
• Known allergy or contraindication to meropenem or azithromycin
• Presence of severe comorbidities (e.g., congenital heart disease, chronic renal failure, immunodeficiency)
• Patients already receiving carbapenem or azithromycin therapy prior to enrollment