Typhoid Fever
Conditions
Brief summary
This randomized controlled trial will compare the effectiveness of single-drug therapy (meropenem) versus combination therapy (meropenem plus azithromycin) in children aged 2-16 years diagnosed with extensively drug-resistant (XDR) typhoid fever at the Children's Hospital, Lahore. A total of 94 patients will be enrolled and randomly assigned to either treatment group. The primary outcome is time to defervescence, defined as sustained resolution of fever for more than 48 hours. Secondary outcomes include duration of hospital stay and complication rates. The study aims to provide evidence to guide optimal management of XDR typhoid in pediatric populations."
Detailed description
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.
Interventions
DRUGmeropenem
IV meropenem, 100 mg/kg/day TDS
DRUGMeropenem and azithromycin combination
combination drug therapy will consist of meropenem intravenously at a dose of 20-40 mg/kg/dose every 8 hours(maximum 2g per dose) plus azithromycin (orally) at 20 mg/kg/day
Sponsors
Iqra Asghar Ali
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria 1. Children aged 2-16 years 2. Culture-confirmed XDR typhoid fever (resistant to first-line agents, fluoroquinolones, and third-generation cephalosporins) 3. Admitted to Children's Hospital \& Institute of Child Health, Lahore Informed consent obtained from parent/guardian
Exclusion criteria
1. Age \<2 years or \>16 years 2. Known allergy or contraindication to meropenem or azithromycin 3. Presence of severe comorbidities (e.g., congenital heart disease, chronic renal failure, immunodeficiency) 4. Patients already receiving carbapenem or azithromycin therapy prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Name: Time to defervescence Description: Number of days from initiation of appropriate antimicrobial therapy until sustained resolution of fever (<100°F for >48 hours). Time Frame: From start of antibiotic therapy upto 10-14 days | Time Frame: 10-14days after initiation of treatment | Description: Number of days from initiation of appropriate antimicrobial therapy until sustained resolution of fever (\<100°F for \>48 hours). |
Countries
Pakistan
Contacts
CONTACTIqra Asghar Ali, mbbs
Outcome results
None listed