Does administration of azithromycin (a macrolide antibiotic) increase the risk for Clostridioides difficile (C. diff) infection?

From the Guidelines

Yes, azithromycin can increase the risk of Clostridioides difficile (C. diff) infection, though it generally carries a lower risk compared to other antibiotics. Azithromycin, like all antibiotics, can disrupt the normal gut microbiota, which allows C. diff to proliferate and produce toxins that cause diarrhea and colitis 1. The risk is particularly increased in elderly patients, those with prolonged hospital stays, patients with prior C. diff infections, immunocompromised individuals, and those taking proton pump inhibitors. While necessary antibiotic treatment should not be withheld due to C. diff concerns, clinicians should use azithromycin judiciously, prescribing it only when clearly indicated, using the shortest effective duration, and considering the patient's individual risk factors. Patients should be monitored for symptoms of C. diff infection such as watery diarrhea, abdominal pain, and fever, particularly during and shortly after antibiotic treatment.

Key Considerations

• The risk of C. diff infection is increased with the use of antibiotics, including azithromycin 1
• The risk is higher in certain patient populations, such as the elderly and those with prolonged hospital stays 1
• Clinicians should use azithromycin judiciously and monitor patients for symptoms of C. diff infection 1
• The use of proton pump inhibitors may also increase the risk of C. diff infection, although the evidence is not conclusive 1

Management of C. diff Infection

• Treatment of C. diff infection typically involves the use of antibiotics such as vancomycin or fidaxomicin 1
• Fecal microbiota transplantation (FMT) may be considered for patients with recurrent C. diff infection 1
• Patients with severe or refractory C. diff infection may require hospitalization and supportive care 1

Prevention of C. diff Infection

• Clinicians should use antibiotics judiciously and only when clearly indicated 1
• Patients should be monitored for symptoms of C. diff infection, particularly during and shortly after antibiotic treatment 1
• Infection control measures, such as hand hygiene and isolation precautions, can help prevent the spread of C. diff in healthcare settings 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.

Yes, administration of azithromycin increases the risk for Clostridioides difficile (C. diff) infection.

• The use of azithromycin, like nearly all antibacterial agents, can alter the normal flora of the colon, leading to overgrowth of C. difficile.
• This overgrowth can cause CDAD, which can range from mild diarrhea to fatal colitis 2.

From the Research

Administration of Azithromycin and C. diff Infection Risk

• The provided studies do not directly investigate the relationship between azithromycin administration and the risk of Clostridioides difficile (C. diff) infection 3, 4, 5, 6, 7.
• However, it is known that antibiotics are a significant risk factor for C. diff infection, with certain types of antibiotics conferring a higher risk than others 3.
• Azithromycin is a macrolide antibiotic, but the studies provided do not specifically examine its association with C. diff infection risk.
• One study notes that non-CDI antibiotic use, which could include azithromycin, increases the risk of C. diff infection recurrence after fecal microbiota transplant 5.
• Another study discusses the adverse effects of long-term azithromycin use, including increased risk of bacterial resistance, but does not mention C. diff infection specifically 6.
• The remaining studies focus on other aspects of azithromycin use, such as its relationship with cardiovascular outcomes in patients with COVID-19 7, and do not provide relevant information on C. diff infection risk.

Relevant Findings on Antibiotic Use and C. diff Infection

• Antibiotics are the most significant risk factor for C. diff infection, with certain types (e.g., cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam) conferring a higher risk than others 3.
• Limiting antibiotic use when possible can help decrease the risk of C. diff infection 3.
• The use of non-CDI antibiotics after successful fecal microbiota transplant increases the risk of C. diff infection recurrence 5.