Does Bactrim (Trimethoprim/Sulfamethoxazole) cause Clostridioides difficile (C. diff) infection?

From the Guidelines

Bactrim (sulfamethoxazole-trimethoprim) can potentially cause Clostridioides difficile (C. diff) infection, though it's not among the highest-risk antibiotics for this complication. Like all antibiotics, Bactrim disrupts the normal balance of bacteria in the gut by killing beneficial bacteria that normally keep C. diff in check. When this protective gut flora is reduced, C. diff bacteria can multiply and produce toxins that cause inflammation and damage to the colon, resulting in symptoms ranging from mild diarrhea to severe, life-threatening colitis. The risk of developing C. diff infection while taking Bactrim increases with longer treatment courses, higher doses, older age, recent hospitalization, and previous C. diff infections.

Key Points to Consider

• Antibiotics most strongly associated with C. diff include clindamycin, fluoroquinolones, and broad-spectrum cephalosporins, but any antibiotic, including Bactrim, carries some risk 1.
• If you develop persistent diarrhea, abdominal pain, or fever while taking Bactrim or within several weeks after finishing treatment, you should contact your healthcare provider promptly as these could be signs of C. diff infection.
• The estimated number of incident CDI cases in the United States was 453,000, with an incidence of 147.2 cases/100,000 persons, and the incidence was highest among those aged ≥65 years 1.
• Recent hospital discharge data indicate that the total number of hospital discharges with a diagnosis of CDI in the United States plateaued at historic highs between 2011 and 2013, and the estimated number of deaths within 30 days of the initial diagnosis of CDI in the United States was 29,300 1.

Management and Prevention

• A prompt and precise diagnosis is an important aspect of effective management of CDI, and early identification of CDI allows the establishment of an early treatment and can improve outcomes 1.
• Rapid isolation of infected patients is fundamental to limit C. difficile transmission, and patients with CDI should be maintained in contact (enteric) precautions until the resolution of diarrhea 1.
• Hand hygiene with soap and water and the use of contact precautions along with a good cleaning and disinfection of the environment and patient equipment should be used by all HCWs contacting any patient with known or suspected CDI 1.

From the FDA Drug Label

Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including sulfamethoxazole and trimethoprim, and may range in severity from mild diarrhea to fatal colitis. Yes, Bactrim (sulfamethoxazole and trimethoprim) can cause C. diff, as it alters the normal flora of the colon leading to overgrowth of C. difficile.

• 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 2.

From the Research

Bactrim and C. Difficile Infection

• Bactrim, an antibiotic, can disrupt the normal intestinal microbiota, which may lead to Clostridioides difficile (C. difficile) infection 3, 4, 5.
• The use of antibiotics, including Bactrim, is a significant risk factor for developing C. difficile infection, especially in elderly and immunocompromised patients 3, 5.
• However, the provided studies do not specifically mention Bactrim as a cause of C. difficile infection, instead focusing on the general risk of antibiotic use 3, 4, 5.

Treatment of C. Difficile Infection

• The cornerstones for the treatment of C. difficile infection are vancomycin and fidaxomicin, with metronidazole being used only in mild-to-moderate disease in younger patients with no or few risk factors for recurrence 3, 4, 6.
• Bezlotoxumab infusion, a monoclonal antibody against C. difficile toxin B, may be considered as an adjunctive therapeutic strategy in addition to standard care for patients with several risk factors for recurrence 3, 4, 7.
• Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring C. difficile infection 3, 4, 5.

Alternative Treatment Approaches

• Alternative treatment approaches, including bacteriophages, endolysins, and tailocins, are being developed to target C. difficile infection 7.
• Restoration of microbiota composition and function through FMT, standardized defined microbial mixtures, and probiotics is also being explored 7, 5.
• Neutralization of C. difficile toxins using antibodies or alternative binding proteins, such as bezlotoxumab, is another area of research 7.