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

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

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."

Study Overview

• Status: Not yet recruiting
• Conditions: Typhoid Fever
• Intervention / Treatment: Drug: meropenem; Drug: Meropenem and azithromycin combination

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.

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Iqra Asghar Ali, mbbs; Phone Number: +923060942498; Email: driqraasghar@GMAIL.COM

Study Locations

• Pakistan
  • Punjab Province
    • Lahore, Punjab Province, Pakistan, 52000
      • University of Child Health Scienes Lahore
      • Contact: Iqra Asghar Ali, mbbs; Phone Number: +923060942498; Email: driqraasghar@GMAIL.COM
      • Principal Investigator: IQRA Asghar Ali, mbbs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meropenem Monotherapy Arm 1; Patients receive meropenem IV, 30mg/kg/dose every 8 hours(maximum 2g per dose)	Drug: meropenem; IV meropenem, 100 mg/kg/day TDS
Experimental: Arm 2 Title: Meropenem + Azithromycin Combination; Patients receive meropenem 30mg/kg/dose every 8 hours (maximum 2g per dose) IV plus oral azithromycin, 20 mg/kg/day.	Drug: Meropenem 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Description: Number of days from initiation of appropriate antimicrobial therapy until sustained resolution of fever (<100°F for >48 hours).	Time Frame: 10-14days after initiation of treatment

Collaborators and Investigators

• Sponsor: Iqra Asghar Ali

Publications and helpful links

General Publications

• Qamar FN, Hussain W, Qureshi S. Salmonellosis Including Enteric Fever. Pediatr Clin North Am. 2022 Feb;69(1):65-77. doi: 10.1016/j.pcl.2021.09.007.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; beta-Lactams; Lactams; Carbapenems; Thienamycins; Meropenem
• Other Study ID Numbers: (XDR-TYPHOID-RCT-2026 UCHS LH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No