Treatment of 21st-Century typhoid fever in children; open-label mono versus combination drug therapy: A multicenter randomized control study.

  • Fatima Ghayas Siddiqi Ziauddin University Hospital, Karachi-Pakistan.
  • Heena Rais Ziauddin University Hospital, Karachi-Pakistan.
  • Farhana Zafar Ziauddin University Hospital, Karachi-Pakistan.
  • Bina . Ziauddin Medical College, Karachi-Pakistan.
  • Tayyaba Anwar Ziauddin Medical College, Karachi-Pakistan.
  • Zain Ally Ziauddin Medical College, Karachi-Pakistan.
  • Aneel Kumar Ziauddin University Hospital, Karachi-Pakistan.
  • Areesha Saleem Dow University of Health Sciences, Karachi-Pakistan
Keywords: Complicated XDR (Extended Drug-Resistant) Typhoid Fever, Meropenum, Azithromycin, Efficacy.


Background: The treatment of 21st Century XDR typhoid fever is potentially life-threatening and endemic in Pakistan, presents a therapeutic challenge as currently there is no universal treatment strategy whether to use monotherapy with meropenum or a combination of meropenum and azithromycin. Our objective was to compare the efficacy of both therapies in complicated XDR typhoid fever in children, regarding defervescence, bacterial clearance time, resolution of complications, hospital stay, and relapse. 

Methodology: This open-label randomized comparative trial was conducted over 18 months at the Department of Pediatrics, Kemari, Clifton and North Campuses, Ziauddin University Hospital Karachi, Pakistan, in which children (aged 6 months to 18 years) with positive blood culture for XDR enteric fever, were recruited into 2 parallel treatment groups (meropenum) and (meropenum+azithromycin combined). Primary outcome viz clinical improvement (resolution of defervescence, complications, and hospital stay) and lab improvement (negative repeat blood culture, 5 days post-treatment), as well as secondary outcome i.e. treatment failure, adverse drug reactions, and relapse of typhoid within 2 weeks post-treatment were monitored.

Results: In the combination group, there was a quicker resolution of fever (5.40 ± 2.17 days vs 6.55 ± 2.77 days in the monotherapy group) as well as complications (3.42 ± 1.97 days vs 4.31 ± 2.71 days in the monotherapy group), resulting in shorter hospital stay (6.94 ± 2.63 days vs 8.08 ± 3.16 days in monotherapy group). 20% had treatment failure in the monotherapy group with a relative risk of 3.55 times more than that in the combination group.  

Conclusion: Combination therapy with meropenum and azithromycin is more efficacious in treating complicated XDR typhoid fever in children than meropenum alone.


Download data is not yet available.


1. Tanmoy AM, Westeel E, De Bruyne K, Goris J, Rajoharison A, Sajib MS, van Belkum A, Saha SK, Komurian-Pradel F, Endtz HP. Salmonella enterica serovar Typhi in Bangladesh: exploration of genomic diversity and antimicrobial resistance. MBio. 2018;9(6):e02112-e02118.
2. Chatham-Stephens K, Medalla F, Hughes M, Appiah GD, Aubert RD, Caidi H, Angelo KM, Walker AT, Hatley N, Masani S, Nash J. Emergence of extensively drug-resistant Salmonella Typhi infections among travelers to or from Pakistan—United States, 2016–2018. Morbidity and Mortality Week Rep. 2019;68(1):11.
3. Kaljee LM, Pach A, Garrett D, Bajracharya D, Karki K, Khan I. Social and economic burden associated with typhoid fever in Kathmandu and surrounding areas: a qualitative study. J Infec Dis. 2018;218(suppl_4):S243-S249.
4. Iftikhar A, Bari A, Jabeen U, Bano I. Spectrum of complications in childhood Enteric Fever as reported in a Tertiary Care Hospital. Pak J Med Sci. 2018;34(5):1115.
5. Britto CD, Wong VK, Dougan G, Pollard AJ. A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid. PLoS Neg Trop Dis. 2018;12(10):e0006779.
How to Cite
Siddiqi, F., Rais, H., Zafar, F., ., B., Anwar, T., Ally, Z., Kumar, A., & Saleem, A. (2021). Treatment of 21st-Century typhoid fever in children; open-label mono versus combination drug therapy: A multicenter randomized control study. International Journal of Endorsing Health Science Research (IJEHSR), 9(3), 384-394.