Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins

Abstract

Background Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low‐ and middle‐income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first‐line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug‐resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first‐line antimicrobials, such as chloramphenicol, has re‐appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. Objectives To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. Selection criteria We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. Main results We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39...

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“…et al (2021) reported that the combination of Azithromycin with other antibiotics led to a quicker resolution of symptoms and a shorter hospital stay (22). Their findings suggested that Azithromycin could play a vital role in enhancing the effectiveness of the treatment for enteric fever (23,24). However, it is essential to observe that the variations in findings could be attributed to differences in study populations, antibiotic resistance patterns, and the strains of pathogens involved.…”

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“…Data derived from a study in Nigeria indicate that oral ciprofloxacin for Salmonella bacteremia seems to be a common practice [28]. Patients receiving ciprofloxacin may have lower rates of microbiological failure and relapse compared to cefixime [29]. However, in a randomized trial from Pakistan, cefixime was as effective as ceftriaxone for bacteremic typhoid fever; more than 8-day treatment may not provide any additional benefit [30,31].…”

Typhoidal Salmonellosis (TS) (Enteric fever)

“…Internal bleeding, bronchitis, pneumonia, and other respiratory issues, inflammation of the heart, inflammation of the bones (osteomyelitis), kidney failure, a swollen or burst gallbladder, intestinal perforation (a hole in the intestine), swelling around the brain (meningitis), neurological (brain) symptoms, and miscarriage are all complications of typhoid fever if it is not treated immediately. [88].…”