Cephalosporin antibiotics for the treatment of enteric fever (typhoid fever)
• There may be no difference in the performance of ceftriaxone (a type of cephalosporin) compared with azithromycin, fluoroquinolones, or chloramphenicol (other antimicrobial medicines) for adults and children with enteric fever (typhoid fever).
• Cefixime (another type of cephalosporin) can also be used for treatment of enteric fever in adults and children but may not be as effective as fluoroquinolones.
• Policymakers and clinicians need to consider local antibiotic resistance patterns when considering treatment options for enteric fever.
What is enteric fever?
Enteric fever is a common term for two similar illnesses known individually as typhoid fever and paratyphoid fever. These illnesses only occur in people and are caused by bacteria known as Salmonellatyphi and Salmonella paratyphi A, B or C. These illnesses are most common in low‐ and middle‐income countries where water and sanitation may be inadequate. Enteric fever typically causes fever and headache with diarrhoea, constipation, abdominal pain, nausea and vomiting, or loss of appetite. If left untreated, some people can develop serious complications and may die.
What are cephalosporins and how might they work?
The cephalosporins are a large family of antimicrobial medicines, which are commonly used to treat a variety of infectious diseases. Individual cephalosporins (such as cefixime and ceftriaxone) vary in the specific bacteria they can treat, how they are given ‐ by mouth (orally) or injected (intravenously) ‐ and when they were developed. Some cephalosporins can treat Salmonellatyphi and Salmonella paratyphi A, B, or C, the bacteria causing enteric (typhoid) fever.
In the past, enteric fever responded extremely well to other types of antimicrobial medicines, such as chloramphenicol. However, bacterial resistance to multiple antimicrobial medicines has become a major public health problem in many areas, especially Asia and Africa. Specific cephalosporins are now often used to treat enteric fever due to evolving drug resistance to other antimicrobials.
What did we want to find out?
We wanted to discover whether cephalosporins are better or worse in treating adults and children with enteric fever compared to other commonly given antimicrobials such as fluoroquinolones and azithromycin. To discover this, we wanted to know if treatment with cephalosporins would lead to persisting symptoms of disease (clinical failure), persisting Salmonellatyphi and Salmonella paratyphi A, B, or C bacteria in blood (microbiological failure), or return of symptoms or Salmonellatyphi and Salmonella paratyphi A, B, or C in the blood (relapse).
We also wanted to know how long cephalosporins take to reduce fever, if they reduce the length of time a patient needs to stay in hospital, whether patients' faeces (stool) would still carry the bacteria and thus remain infectious, and whether they cause any unwanted effects in patients.
What did we do?
We searched for studies that compared the treatment of a cephalosporin antimicrobial to another type of antimicrobial, or compared the treatment of a cephalosporin antimicrobial to another different cephalosporin antimicrobial, in adults or children who had enteric fever diagnosed through a laboratory test, such as blood culture.
What did we find?
We identified 27 studies involving 2231 adults and children from Africa, Asia, Europe, the Middle East, and the Caribbean that compared cephalosporin antimicrobial treatment in enteric fever with other antimicrobials.
Ceftriaxone was found to be an effective treatment for enteric fever, with few unwanted effects, and was similar to azithromycin, fluoroquinolones and chloramphenicol in its ability to treat enteric fever.
Cefixime can also be used to treat enteric fever but may not perform as well when compared to fluoroquinolone antimicrobials.
These findings only apply if the bacteria causing the enteric fever infection is vulnerable to the antimicrobial given to treat the infection; that is, the bacteria is not resistant to the antimicrobial.
What are the limitations of the evidence?
We have low confidence in our estimates, for these findings because of the low number of patients in the included studies. Also, in most included studies patients and doctors knew which antimicrobial the patient was receiving, which could have biased the results.
How up to date is this evidence?
These results are current up to 24 November 2021.
Kuehn R, Stoesser N, Eyre D, Darton TC, Basnyat B, Parry CM. Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins. Cochrane Database of Systematic Reviews 2022, Issue 11. Art. No.: CD010452. DOI: 10.1002/14651858.CD010452.pub2.
The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government's offical policies.