Which antibiotic class is broadly associated with C. difficile infection risk and should be used with caution?

• A. Penicillins
• B. Macrolides
• C. Aminoglycosides
• D. Broad-spectrum cephalosporins

Answer: (D)

The key idea is that antibiotics that broadly disrupt the gut microbiota increase the risk of C. difficile overgrowth and toxin production. Broad-spectrum cephalosporins wipe out a wide range of gut bacteria, including anaerobes that normally keep C. difficile in check. With these competitors knocked out, C. difficile can flourish and cause infection, so these drugs are notably linked to CDI and should be used with caution, especially in patients at higher risk or in high-CDI settings.

Penicillins can cause CDI but generally have a smaller impact on the gut flora compared with broad-spectrum cephalosporins. Macrolides and aminoglycosides tend to have less effect on gut bacterial diversity or have limited gut exposure, so their CDI risk is comparatively lower.