Antimicrobial agents for the treatment of enteric fever chronic carriage: A systematic review

Abstract

BackgroundChronic carriage of S. Typhi or S. Paratyphi is an important source of enteric fever transmission. Existing guidance and treatment options for this condition are limited. This systematic review aims to assess the evidence concerning the efficacy of different antimicrobials in treating enteric fever chronic carriage.MethodsWe searched major bibliographic databases using relevant keywords between 1946 and September 2021. We included all interventional studies that included patients with confirmed enteric fever chronic carriage and deployed an antimicrobial that remains in clinical practice today. Case reports and case series of under 10 patients were excluded. Two reviewers screened abstracts, selected articles for final inclusion and quality-assessed the included studies for risk of bias. Extracted data was analysed, with pooling of data and eradication rates for each antimicrobial calculated. As only one randomised controlled trial was identified no meta-analysis was performed.ResultsOf the 593 papers identified by the initial search, a total of eight studies met the inclusion criteria and were included in the systematic review. Evidence was identified for the use of fluoroquinolones and amoxicillin/ampicillin in the treatment for enteric fever chronic carriage. Fluoroquinolones were superior to amoxicillin/ampicillin with 92% of patients eradicated after one antimicrobial course compared to 68% (p = 0.02). The quality of included studies was poor, and all were carried out before 1990.ConclusionThis review identified fluoroquinolones and amoxicillin as treatment options for enteric fever chronic carriage, with fluoroquinolones the more effective option. However, this evidence pre-dates rises in antimicrobial resistance in enteric fever and therefore the significance of these findings to today’s practice is unclear. Further research is needed to investigate whether these antimicrobials remain appropriate treatment options or whether alternative interventions are more effective.Author summaryThere are more than 14 million cases of enteric fever every year globally. The rise of antimicrobial resistance against S. Typhi and S. Paratyphi, the pathogens causing enteric fever, has led to limited treatment options against this condition. Mechanisms to prevent infection are therefore becoming increasingly important. Public health measures and, more recently, the development and rollout of the typhoid conjugate vaccine, are going some way towards reducing transmission of this condition but identification and treatment of enteric fever chronic carriers has been neglected.S. Typhi and S. Paratyphi are restricted to human hosts and transmitted via the ingestion of contaminated food or water. Chronic carriers, those who asymptomatically excrete the pathogens in their stool following infection, play an important role in maintaining the reservoir of infection within humans. Identification and treatment of these carriers will be vital in further reducing transmission of enteric fever and ultimately eliminating this condition.Here we review the evidence for antimicrobials in treating enteric fever chronic carriage. We identify evidence for fluoroquinolones and amoxicillin as treatment strategies but highlight large gaps in the literature on this subject, including a lack of evidence in the antimicrobial-resistant era of enteric fever.