What is the rationale for using chloramphenicol (Chloramphenicol) in the treatment of typhoid fever?

From the Guidelines

Chloramphenicol is recommended as a last-resort option for the treatment of enteric fever, including typhoid fever, when no other antibiotics are available, due to its potential effectiveness despite concerns about serious adverse effects 1. The rationale for the use of chloramphenicol in the treatment of typhoid fever is based on its ability to inhibit bacterial protein synthesis, preventing Salmonella Typhi from replicating, and its excellent tissue penetration, including the gallbladder where typhoid bacteria may persist.

• The standard dosage for adults is 50-100 mg/kg/day divided into four doses (every 6 hours) for 14-21 days, with pediatric dosing at 50-75 mg/kg/day divided similarly.
• Chloramphenicol was once considered the gold standard treatment for typhoid fever, but it has been largely replaced by fluoroquinolones and third-generation cephalosporins due to concerns about serious adverse effects, particularly bone marrow suppression and aplastic anemia (occurring in approximately 1 in 30,000 patients) 1.
• Regular blood count monitoring is essential during treatment with chloramphenicol.
• Today, chloramphenicol is primarily used in resource-limited settings where newer antibiotics are unavailable or unaffordable, or in cases of multidrug-resistant typhoid when susceptibility testing confirms its effectiveness. Some guidelines, such as the World Health Organization (2012), recommend fluoroquinolones as the first-line treatment for typhoid fever, with third-generation cephalosporins or azithromycin as alternative options 1.
• However, in cases where these options are not available or effective, chloramphenicol may be considered as a last-resort option. It is essential to note that the use of chloramphenicol should be carefully considered, taking into account the potential risks and benefits, and that regular monitoring of blood counts is crucial to minimize the risk of adverse effects.
• The decision to use chloramphenicol should be made on a case-by-case basis, considering the individual patient's circumstances and the availability of other treatment options.

From the FDA Drug Label

In accord with the concepts in the Warning Box and this INDICATIONS AND USAGE section, chloramphenicol must be used only in those serious infections for which less potentially dangerous drugs are ineffective or contraindicated • Acute infections caused by Salmonella typhi* *In treatment of typhoid fever some authorities recommend that chloramphenicol be administered at therapeutic levels for 8 to 10 days after the patient has become afebrile to lessen the possibility of relapse.

The rationale for the use of chloramphenicol in the treatment of typhoid fever is that it is effective against Salmonella typhi and can be used when less potentially dangerous drugs are ineffective or contraindicated. Additionally, administering chloramphenicol at therapeutic levels for 8 to 10 days after the patient has become afebrile may help to lessen the possibility of relapse 2.

From the Research

Rationale for Chloramphenicol Use

The use of chloramphenicol in the treatment of typhoid fever is based on several studies that have compared its efficacy with other antibiotics. Some key points to consider include:

• Chloramphenicol has been shown to be effective in reducing the duration of fever in patients with typhoid fever, with a clinical cure rate of 90% in one study 3.
• The drug has been compared to ceftriaxone, with one study finding that chloramphenicol was more effective in achieving clinical cure, although ceftriaxone had a faster effect on blood cultures 3.
• Chloramphenicol has also been compared to other antibiotics, such as ampicillin and co-trimoxazole, with one study finding that it was more effective in reducing the duration of fever 4.
• However, the use of chloramphenicol is not without risks, as it can cause bone marrow suppression and has a history of plasmid-mediated resistance 5.

Comparison with Other Antibiotics

Some studies have compared the efficacy of chloramphenicol with other antibiotics, including:

• Ceftriaxone: Chloramphenicol was found to be more effective in achieving clinical cure, although ceftriaxone had a faster effect on blood cultures 3.
• Azithromycin: Azithromycin has been shown to be effective in the treatment of typhoid fever, with a clinical cure rate of 91% in one study 6.
• Fluoroquinolones: Fluoroquinolones, such as gatifloxacin, have been shown to be effective in the treatment of typhoid fever, particularly in areas where there is decreased ciprofloxacin susceptibility 5.

Considerations for Use

The use of chloramphenicol in the treatment of typhoid fever should be considered in the context of the following:

• Efficacy: Chloramphenicol has been shown to be effective in reducing the duration of fever and achieving clinical cure in patients with typhoid fever.
• Safety: Chloramphenicol can cause bone marrow suppression and has a history of plasmid-mediated resistance.
• Resistance: The use of chloramphenicol should be guided by susceptibility testing, as resistance can develop 5.