Antimicrobial therapy of acute diarrhoea: a clinical review

ABSTRACT

Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.

KEYWORDS:

• Antimicrobial therapy
• GI tract
• diarrhoea
• gastroenteritis
• Clostridium difficile
• colonisation
• infection
• resistance

Acknowledgements

Native language support was provided by Rodney Yeates, M.A.

Financial & competing interests disclosure

The author received financial support for consulting, lecture fees, and travel costs from Astellas, InfectoPharm, MSD, Novartis, and Pfizer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Infectious diarrhea is one of the most common diseases in the world; according to the World Health Organization (WHO), it is one of the five most important causes of death, especially in children under 5 years of age.

• Symptomatic therapy is still the most important component of the treatment of infectious diarrhea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools (arbitrarily >6/day), symptoms persisting for >1 week, fever, bloody diarrhea, underlying immune deficiency, advanced age or significant comorbidities.

• Increasing resistance, in particular against fluoroquinolones, must be taken into consideration and profound knowledge of local resistance patterns is required, especially in patients with TD. In a recent study, empirical antibiotic therapy for TD proved to be independent risk factors, with up to 80% of symptomatic travellers contracting ESBL-producing Enterobacteriaceae.

• Antimicrobial therapy of patients with STEC infection is not recommended. In this case, the risk of unfavorable effects, particularly HUS, clearly outweighs the effects of rapid pathogen reduction, which may anyway only be achieved if the drug is used at a very early stage. However, therapy with azithromycin appears to have a favorable effect on the long-term EHEC/STEC carrier status.

• Infections from non-typhoidal Salmonella normally exhibit a self-limiting course and do not require antibiotic therapy, as this can prolong pathogen elimination. Specific antimicrobial therapy is indicated for severe invasive courses, sepsis, and patients in the first year of life, very aged patients, patients with inborn or acquired immune defects and patients with known anomalies or prosthetic replacement to heart valves or vessels, even when the disease is purely gastroenteritic.

• Diarrhea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDIs. Furthermore, evidence for the benefits of FMT as a treatment option for multiple recurrences of CDI is increasing, and establishment of oral, capsulized, frozen fecal microbiota transfer has already successfully passed pilot studies.

• Therapy with motility inhibitors is not recommended for STEC infections, CDI, and severe colitis.

• A major clinical challenge in assessing patients with acute diarrhea is the decision of when to test for causative pathogens, which then should lead to targeted antimicrobial therapy. In severely ill patients with significant dehydration, fever, bloody diarrhea, underlying immune deficiency, recent use of antibiotics, advanced age, significant comorbidities or hospitalization, primary evaluation of stool specimen for bacterial agents (Salmonella, Campylobacter, and Shigella species), STEC, and CDI should be performed.