Latest Treatment of Typhoid Fever: Gastroenterologist Explains.

Our content is not intended nor recommended as a substitute for medical advice by your doctor. Use for informational purposes only.

NOTE: THIS ARTICLE IS MAINLY INTENDED FOR HEALTHCARE PROFESSIONALS.

What you need to know:

  • Typhoid fever treatment is challenging nowadays due to emerging Multidrug-resistant (MDR) and Extensively drug-resistant (EDR) strains.
  • Use intravenous antibiotics for severe or complicated typhoid fever. In addition, oral medications are only allowed in mild or uncomplicated typhoid fever.
  • Ciprofloxacin and ceftriaxone are the two most commonly used regiments for typhoid fever.
  • Areas with EDR strains (such as Afghanistan and Iraq) may require azithromycin therapy with remains effective for such strains.
  • A two-day dexamethasone therapy can be given in severe or complicated typhoid fever.

Why is the treatment of typhoid fever challenging nowadays?

Typhoid fever is a result of infection with a bacteria called salmonella. Typhoid fever (also called enteric fever) typically causes fever and abdominal pain.

Salmonella bacteria are rapidly adapting to the commonly used antibiotics. The global spread of multi-drug-resistant and extremely drug-resistant typhoid fever is challenging nowadays.

Multidrug-resistant (MDR) salmonella:

They’re strains that are resistant to (reference):

  • Ampicillin antibiotics.
  • Trimethoprim-Sulfamethoxazole.
  • Chloramphenicol.

Multidrug-resistant typhoid is widespread everywhere worldwide nowadays.

MDR typhoid fever also caused outbreaks in several regions. Common endemic areas are south and southeast Asia, China, and Africa.

MDR typhoid fever reaches up to 80% of the cases in the endemic areas (reference).

Fluoroquinilone resistance.

After the first wave of (multidrug-resistant typhoid fever), the newer strains also became resistant to fluoroquinolones (ciprofloxacin).

In some parts of South Asia, more than 80% of Salmonella Typhi strains are resistant to fluoroquinolones (reference).

Extensively drug-resistant (EDR) salmonella.

Resistance to other agents such as ceftriaxone and other antibiotics is increasing nowadays.

In 2016, a large outbreak of typhoid fever was caused by an Extensively drug-resistant strain (to chloramphenicol, ampicillin, Trimethoprim-sulfamethoxazole, ciprofloxacin, and third-generation cephalosporin is reported (reference).

So, The organism causing typhoid fever is constantly evolving and developing new resistance patterns. Therefore, the latest treatments of typhoid fever are changing according to these new patterns.

The common medications for Typhoid fever Treatment.

The ultimate treatment depends on resistance testing (culture and sensitivity tests).

However, these tests take the time or might be unavailable in certain places.

Treatment of typhoid fever follows two strategies:

  1. Empiric therapy: treatment that doesn’t wait for resistance testing.
  2. Directed therapy: therapy according to culture and sensitivity testing.

Below, we will discuss the latest empiric treatment of typhoid fever. However, the below suggestion is used only while waiting for culture and sensitivity testing.

Also, Empiric therapy is used if the testing is unavailable. Otherwise, typhoid fever treatment depends on the results of resistance testing (directed therapy).

A. Severe or complicated disease:

An intravenous antibiotic is preferred in severe or complicated typhoid fever.

  • Infection in areas without EDR strains: Cefotraixone or cefotaxime antibiotics (third-generation cephalosporins).
  • Infection in areas with EDR (Afghanistan and Iraq): carbapenems (such as imipenem and meropenem).

The Doses and duration of the antibiotics are illustrated in the table below.

The criteria of severe or complicated diseases include:

  • Depressed consciousness (confusion or coma).
  • Prolonged fever.
  • Organ failure (such as liver failure or kidney failure).
  • Intestinal perforation.
  • Or any other complication that requires admission to the hospital.

B. Treatment of the uncomplicated disease.

The Empiric therapy of uncomplicated disease depends on the local resistance patterns to fluoroquinolones (ciprofloxacin).

Oral tablets are allowed in the treatment of uncomplicated typhoid fever

  • Ciprofloxacin: given in areas without known resistance to fluoroquinolones.
  • Azithromycin or ceftriaxone: in areas with know resistance to fluoroquinolones.
  • Azithromycin only (not ceftriaxone): in Pakistan and Iraq due to the high prevalence of EDR strains.

NOTE: You should adjust or change these regiments after the results of culture and sensitivity testing.

The below table was acquired from uptodate.com (reference).

 AdultsChildrenDuration
CiprofloxacinOral: 500 mg twice dailyOral: 30 mg/kg per day in two divided doses (maximum 1000 mg per day)*7 to 10 days
IV: 400 mg twice dailyIV: 20 mg/kg per day in two divided doses (maximum 800 mg per day)*
Ofloxacin400 mg orally or IV twice daily15 to 30 mg/kg per day orally in two divided doses (maximum 800 mg per day)*¶ based upon limited experience; optimal pediatric dose is not known7 to 10 days
Ceftriaxone2 g IV once or twice daily50 to 100 mg/kg IV in one or two divided doses (maximum 4 g per day)10 to 14 days
Cefotaxime1 to 2 g IV every six or eight hours150 to 200 mg/kg IV per day in three to four divided doses (maximum 8 g per day)10 to 14 days
Cefixime200 mg orally twice daily20 mg/kg orally in two divided doses (maximum 400 mg per day)10 to 14 days
Azithromycin1 g orally once, then 500 mg orally daily OR 1 g orally once daily10 to 20 mg/kg orally once per day (maximum 1000 mg per day)5 to 7 days
Meropenem1 to 2 g IV every eight hours20 to 40 mg/kg every eight hours (maximum 6000 mg per day)10 to 14 days

 

Latest treatments Extretremely drug-resistant (EDR) typhoid fever.

Patients in areas with Extensively drug-resistant strains often become resistant to ciprofloxacin and ceftriaxone treatment.

Ciprofloxacin and ceftriaxone are the two most commonly used treatments for typhoid fever. However, they’re no longer effective for the EDR strains.

Fortunately, The EDR appears to remain susceptible to large dose azithromycin.

Azithromycin dose for typhoid fever is 1 gm once daily for 5-7 days (reference).

How to diagnose and treat relapse of typhoid fever.

Relapse of typhoid fever is common even if you have a competent immune system. Typically, fever and other symptoms resolve within 3-5 days after the initiation of treatment.

The relapse of typhoid fever typically occurs 2-3 weeks after the resolution of symptoms.

Newer antibiotics have a lower rate of relapse (about 1-6 percent) (reference).

Suspect a relapse when the same symptoms (fever and abdominal pain) reappear after weeks of improvement.

The relapse is confirmed by culture and sensitivity testing.

The treatment of relapse often requires directed therapy (according to the culture and sensitivity testing). This helps prevention of future recurrence and the development of new resistant strains.

Typhoid fever treatments that are not currently useful.

The below treatments were previously used for the treatment of typhoid fever. However, they’re no longer recommended as first-line treatment because of the widespread resistance (reference).


Medications of limited efficacy for Typhoid fever treatment.
ChloramphenicolOral: 500 to 750 mg four times per day50 to 100 mg/kg per day orally or IV in four divided doses (maximum 3 g per day)14 to 21 days
IV: 50 to 100 mg/kg per day in four divided doses (maximum 3 g per day)
Amoxicillin1 g orally three times daily100 mg/kg per day orally in three divided doses (maximum 3 g per day)10 to 14 days
TMP-SMXOne double-strength tablet (160/800 mg) orally twice daily8 mg/kg TMP and 40 mg/kg SMX orally in two or four divided doses (maximum 320 mg TMP/1600 mg SMX per day)10 to 14 days

Important tips on the latest treatments of typhoid fever.

  • You can give Dexamethasone (3mg/kg then 1 mg/kg every 6 hours for a total of 48 hours) in complicated or severe typhoid fever.
  • A chronic carrier state of salmonella can develop. The carriers continue to shed the organism in their feces. Therefore, the treatment of carriers is essential to prevent the spread in the community.
  • The WHO recommends taking the typhoid vaccine in areas with endemic typhoid fever.
  • Make sure you give the proper doses and duration (illustrated above). This is important because the doses of antibiotics are often higher than the conventional dosing. For example (ceftriaxone 2 g per day and azithromycin 1 g per day).

MORE:

  • Signs of Recovery from Typhoid Fever: Gastroenterologist Explains.

  • Typhoid Effects on Lungs & Spread through cough.

  • Laboratory Diagnosis of Typhoid fever (for Healthcare practitioners).

Suggested Readings for healthcare professionals:

https://pubmed.ncbi.nlm.nih.gov/32491445/

https://www.uptodate.com/contents/treatment-and-prevention-of-enteric-typhoid-and-paratyphoid-fever/

https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/typhoid-and-paratyphoid-fever

  • Evidence-based
  • Written by a doctor.
MD, Associate Lecturer of Gastroenterology and hepatology. An IBS sufferer, gut health enthusiast and writer.
Dr. I. Farahat
Dr. I. FarahatAuthor
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