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 nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis. The use of nitrofurantoin may exacerbate Clostridioides difficile (C. diff) infection, as it can alter the normal flora of the colon leading to overgrowth of C. difficile.
- Key points:
- CDAD can range from mild diarrhea to fatal colitis
- 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
- CDAD must be considered in all patients who present with diarrhea following antibiotic use 1
From the Research
Nitrofurantoin and C. diff Infection
- The relationship between Nitrofurantoin (Macrobid) and Clostridioides difficile (C. diff) infection is complex, with some studies suggesting a potential link between the use of Nitrofurantoin and an increased risk of C. diff infection 2, 3.
- A 2022 study found that Nitrofurantoin was associated with C. diff infection, particularly among older patients with risk factors for the infection, with an adjusted odds ratio of 3.05 (95% CI, 1.92 to 4.84) 2.
- Another study from 2021 found that ciprofloxacin had a higher risk of C. diff infection compared to Nitrofurantoin, with an adjusted relative risk of 1.89 (95% CI, 1.45 to 2.68) 3.
- However, it is essential to note that the risk of C. diff infection is not unique to Nitrofurantoin and can be associated with the use of various antibiotics, including clindamycin, cephalosporins, and fluoroquinolones 4, 5, 6.
Comparative Risks of Antibiotics
- The comparative risks of different antibiotics for C. diff infection have been studied, with some antibiotics found to have a higher risk than others 2, 3, 6.
- A 2022 study found that clindamycin, cefdinir, cefuroxime, and fluoroquinolones had a higher risk of C. diff infection compared to doxycycline, while Nitrofurantoin had a lower risk but still a significant association with C. diff infection 2.
- Another study from 2021 found that the risk of C. diff infection increased with the duration of antibiotic use, with longer courses of antibiotics associated with a higher risk of infection 3.
Clinical Implications
- The use of Nitrofurantoin and other antibiotics should be judicious and based on careful consideration of the potential risks and benefits, particularly in patients with risk factors for C. diff infection 4, 2, 5, 3, 6.
- Antimicrobial stewardship programs that promote the responsible use of antibiotics are essential for reducing the risk of C. diff infection and other healthcare-associated infections 2, 6.