Typhoid Fever Medication

Updated: Mar 25, 2022
  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...


Class Summary

Since 2016, Salmonella typhi, and to a lesser extent Salmonella paratyphi, have progressively developed resistance to the previously effective antibiotics. Multi-drug-resistant (MDR) typhoid is resistant to ampicillin, trimethoprim sulfamethoxazole, and chloramphenicol. XDR – typhoid has become resistant to chloramphenicol ampicillin, floroquinolones, and third generation cephalosporins. Only azithromycin, members of the carbapenem class, and tigecycline remain effective against XDR isolates.

Since recognition of XDR typhoid fever has been documented in the United States among those who did not travel internationally, appropriate treatment for this disease should consist of azithromycin with or without addition of a carbapenem depending on the severity of the clinical presentation. [49, 50, 51]

Development of MDR and XDR strains has occurred primarily in Pakistan. Most likely, poor sanitation and overuse of antibiotics for the treatment of other infections have been the major reasons for the rapid rise of resistance in Pakistan and other similar countries.The marked increase in density of the urban population in Karachi and other cities clearly facilitates spread of these variants.

The medical complications of COVID-19 have already stressed the medical resources of Pakistan. Many do not want to risk perceived, possible exposure to this virus at various healthcare sites. The marked increase in population density in large cities such as Karachi has facilitated the spread of this pathogen.

Mass immunization campaigns to control typhoid have been thwarted because of religious and cultural prejudices. 


Azithromycin (Zithromax)

Treats mild to moderate microbial infections. Administered PO at 10 mg/kg/d (not exceeding 500 mg), appears to be effective to treat uncomplicated typhoid fever in children 4-17 y. Confirmation of these results could provide an alternative for treatment of typhoid fever in children in developing countries, where medical resources are scarce.



Class Summary

Dexamethasone may decrease the likelihood of mortality in severe typhoid fever cases complicated by delirium, obtundation, stupor, coma, or shock if bacterial meningitis has been definitively ruled out by cerebrospinal fluid studies. To date, the most systematic trial of this has been a randomized controlled study in patients aged 3-56 years with severe typhoid fever who were receiving chloramphenicol therapy. This study compared outcomes in 18 patients given placebo with outcomes in 20 patients given dexamethasone 3 mg/kg IV over 30 minutes followed by dexamethasone 1 mg/kg every 6 hours for 8 doses. The fatality rate in the dexamethasone arm was 10% versus 55.6% in the placebo arm (P =.003). [52]

Nonetheless, this point is still debated. A 2003 WHO statement endorsed the use of steroids as described above, but reviews by eminent authors in the New England Journal of Medicine (2002) [4] and the British Medical Journal (2006) [53] do not refer to steroids at all. A 1991 trial compared patients treated with 12 doses of dexamethasone 400 mg or 100 mg to a retrospective cohort in whom steroids were not administered. This trial found no difference in outcomes among the groups. [54]

The data are sparse, but the authors of this article agree with the WHO that dexamethasone should be used in cases of severe typhoid fever.

Dexamethasone (Decadron)

Prompt administration of high-dose dexamethasone reduces mortality in patients with severe typhoid fever without increasing incidence of complications, carrier states, or relapse among survivors.