What is the current management of typhoid (Salmonella Typhi) fever?

From the Guidelines

The current management of typhoid fever should prioritize the use of third-generation cephalosporins like ceftriaxone (2g IV once daily for adults, 50-75 mg/kg for children, for 10-14 days) or azithromycin (1g on day one, then 500 mg daily for 5-7 days) as first-line treatment due to increasing fluoroquinolone resistance, as recommended by the most recent guidelines 1.

Key Considerations

• The choice of antibiotic should be guided by local resistance patterns and the severity of the disease.
• Fluoroquinolones, such as ciprofloxacin, are no longer the first-line treatment due to high resistance rates, with more than 70% of isolates of S. typhi and S. paratyphi imported into the UK being resistant to fluoroquinolones 1.
• Azithromycin is a suitable oral alternative for uncomplicated disease, with resistance being currently rare in the UK 1.
• Cefixime, another alternative oral first-line agent, has reported treatment failure rates of 4-37.6% 1.

Treatment Approach

• Empirical treatment should be started promptly in patients with a strong suspicion of enteric fever and unstable clinical condition, pending blood culture results 1.
• The duration of treatment should be adjusted based on clinical response, with longer courses needed for complicated infections or persistent fever.
• Supportive care, including adequate hydration, antipyretics for fever, and close monitoring for complications, is crucial in the management of typhoid fever.

Prevention of Complications

• Patients should be isolated until three consecutive stool cultures are negative to prevent the spread of the disease.
• Close monitoring for complications such as intestinal perforation, hemorrhage, and encephalopathy is essential, as these can occur in up to 15% of patients, especially if the duration of illness is more than 2 weeks 1.

From the FDA Drug Label

Typhoid Fever (Enteric Fever) caused by Salmonella typhi. The current management of typhoid fever includes the use of ciprofloxacin for the treatment of infections caused by Salmonella typhi.

• The FDA drug label for ciprofloxacin indicates that it is effective for the treatment of typhoid fever.
• However, it is essential to note that the efficacy of ciprofloxacin in eradicating the chronic typhoid carrier state has not been demonstrated 2.

From the Research

Current Management of Typhoid Fever

The current management of typhoid fever involves the use of antibiotics, with the choice of antibiotic depending on the severity of the disease, the patient's age, and the presence of any underlying medical conditions.

• The World Health Organization (WHO) recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials 3.
• A study published in 2021 found that combined treatment with azithromycin and cefixime may be a better option for the treatment of clinically suspected and culture-confirmed typhoid fever in South Asia 4.
• Another study published in 2018 found that combined therapy of third-generation cephalosporins and azithromycin for typhoid fever may surpass monotherapy in terms of fever clearance time and time to elimination of bacteremia 5.

Antibiotic Options

Several antibiotic options are available for the treatment of typhoid fever, including:

• Azithromycin: a macrolide antibiotic that is effective against typhoid fever and has been shown to be superior to other antibiotics in some studies 6.
• Ceftriaxone: a third-generation cephalosporin that is effective against typhoid fever and is often used as a backup choice 3, 6.
• Cefixime: a third-generation cephalosporin that is effective against typhoid fever, but may not perform as well as fluoroquinolones 3.
• Ciprofloxacin: a fluoroquinolone antibiotic that is effective against typhoid fever, but resistance to this antibiotic is increasing in some parts of the world 3, 6.

Treatment Duration and Outcomes

The duration of treatment for typhoid fever typically ranges from 5 to 14 days, depending on the severity of the disease and the patient's response to treatment.

• A study published in 2019 found that the mean duration of treatment with ceftriaxone was six days, and that an additional antibiotic was needed in some patients due to clinical non-response 7.
• Another study published in 2018 found that combined therapy with azithromycin and ceftriaxone resulted in a shorter fever clearance time and time to elimination of bacteremia compared to monotherapy 5.