What is the role of azithromycin (AZI) in treating diarrhea?

From the Guidelines

Azithromycin syrup should be considered for the treatment of diarrhea only when there is confirmed or strongly suspected bacterial infection, particularly from pathogens like Shigella, Campylobacter, or certain strains of E. coli, as it has been shown to be effective in reducing symptom duration and is generally well-tolerated 1.

Key Considerations

• The decision to treat diarrhea with azithromycin should be based on the severity of illness and the presence of bacterial infection, as antibiotics are not effective against viral or self-limiting diarrhea.
• Azithromycin has been demonstrated to be effective in treating bacterial diarrhea, particularly in cases of dysentery or acute watery diarrhea with greater than mild fever, due to its broad-spectrum activity against common bacterial pathogens such as Shigella, Campylobacter, and enteroinvasive E. coli.
• The typical azithromycin dosage for children is 10 mg/kg on day 1 (maximum 500 mg), followed by 5 mg/kg daily for 2-4 more days depending on the severity and pathogen, while for adults, 500 mg on day 1 followed by 250 mg daily for 2-4 days is common.
• It is essential to complete the full prescribed course of azithromycin even if symptoms improve, to ensure the infection is fully cleared and to minimize the risk of antibiotic resistance.
• Azithromycin works by inhibiting bacterial protein synthesis, preventing bacterial growth and reproduction, and has been shown to be superior to levofloxacin in achieving clinical cure in certain settings with high rates of fluoroquinolone-resistant Campylobacter spp. 1.

Potential Side Effects and Interactions

• Azithromycin is generally well-tolerated, with minimal side effects, usually dose-related gastrointestinal complaints, and incident or worsening nausea or vomiting, which are more common than in the treatment of non-gastrointestinal infections.
• The use of azithromycin should be avoided in patients with a history of allergic reactions to macrolides, and caution should be exercised when using azithromycin in patients with liver or kidney disease.
• Azithromycin may interact with other medications, such as warfarin, and may increase the risk of QT interval prolongation, particularly when used in combination with other medications that prolong the QT interval.

Evidence Summary

• A study published in the Journal of Travel Medicine in 2017 found that azithromycin was effective in reducing symptom duration in travelers' diarrhea, and was superior to levofloxacin in achieving clinical cure in certain settings with high rates of fluoroquinolone-resistant Campylobacter spp. 1.
• Another study published in Clinical Infectious Diseases in 2017 found that azithromycin was effective in treating bacterial diarrhea, particularly in cases of dysentery or acute watery diarrhea with greater than mild fever, due to its broad-spectrum activity against common bacterial pathogens such as Shigella, Campylobacter, and enteroinvasive E. coli 1.

From the FDA Drug Label

Clostridium Difficile-associated diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Azithromycin and Diarrhea: Azithromycin can cause Clostridium difficile-associated diarrhea (CDAD), which may range from mild to fatal colitis.

• Key Points:
  • CDAD can occur after azithromycin use
  • Careful medical history is necessary to diagnose CDAD
  • If CDAD is suspected, azithromycin may need to be discontinued
  • Appropriate management, including fluid and electrolyte management and antibiotic treatment, should be instituted as clinically indicated 2

From the Research

Syrup Azithromycin in Diarrhea

• Azithromycin represents an alternative option to treat bacterial diarrhea when antibiotic therapy is indicated 3.
• A study found that all strains of Salmonella non-typhi, Shigella, and Yersinia, except one, had a MIC≤16mg/L of azithromycin, suggesting that azithromycin would be a useful antibiotic alternative to treat bacterial diarrhea 3.
• However, the World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea, and a randomized clinical trial found that the addition of azithromycin to standard case management of acute nonbloody watery diarrhea did not detect a survival benefit for children in low-resource settings 4.
• Another study found that symptomatic therapy is still the most important component of the treatment of infectious diarrhea, but empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhea, underlying immune deficiency, advanced age, or significant comorbidities 5.
• A reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) trial incorporating molecular diagnostics found that azithromycin treatment was associated with a reduced risk of diarrhea on day 3 and 90-day hospitalization or death among children with a likely or possible bacterial etiology 6.
• A machine learning study developed personalized treatment rules for azithromycin treatment in children with watery diarrhea and found that treatment was recommended on average for approximately one third of children, with a reduced risk of diarrhea on day 3 and 90-day re-hospitalization and death among those recommended for treatment 7.