Clindamycin and Clostridioides difficile-Associated Diarrhea
The correct answer is C: Clindamycin has been strongly associated with development of Clostridioides difficile-associated diarrhea and colitis, which is explicitly stated in FDA labeling and multiple clinical guidelines. 1
Analysis of Each Statement
Statement C (CORRECT): C. difficile-Associated Diarrhea Risk
Clindamycin carries a well-established and significant risk for C. difficile infection (CDI), documented across FDA labeling, clinical guidelines, and decades of clinical evidence.
The FDA drug label contains a black box warning specifically stating that clindamycin therapy "has been associated with severe colitis which may end fatally" and that C. difficile-associated diarrhea (CDAD) has been reported with clindamycin use, ranging from mild diarrhea to fatal colitis 1
The IDSA guidelines identify clindamycin as one of the antibiotics most strongly associated with CDI development, alongside cephalosporins, β-lactam/β-lactamase inhibitors, and quinolones 2
Clindamycin is consistently listed among the highest-risk antibiotics for CDI across multiple guideline sources 3, 4
Historical data from the 1970s-1980s established clindamycin as the most common causative agent for antibiotic-associated colitis, with early landmark studies identifying C. difficile as the pathogen responsible for clindamycin-induced pseudomembranous colitis 5, 6
A hospital-wide restriction of clindamycin resulted in a sustained 65% reduction in C. difficile cases (from 11.5 to 3.33 cases/month), demonstrating the direct causal relationship 7
Statement A (INCORRECT): Hospital-Acquired MRSA Activity
Clindamycin does not possess good activity against hospital-acquired MRSA. While clindamycin may have activity against some community-acquired MRSA strains, hospital-acquired MRSA typically demonstrates high rates of clindamycin resistance, making it an unreliable choice for empiric therapy in this setting.
Statement B (INCORRECT): First-Line for Intra-Abdominal Infections
Clindamycin is not a first-choice agent for anaerobic coverage in active intra-abdominal infections. Current guidelines favor broader-spectrum agents with more reliable anaerobic coverage, such as metronidazole combined with other agents, or β-lactam/β-lactamase inhibitor combinations. The high resistance rates to clindamycin among anaerobes (59% weighted pooled resistance) further limit its utility 8
Statement D (INCORRECT): CYP3A4 Inhibition
Clindamycin is not a significant inhibitor of CYP3A4 enzymes. This statement confuses clindamycin with other antibiotics (such as macrolides like erythromycin and clarithromycin) that are known CYP3A4 inhibitors.
Clinical Implications of C. difficile Risk
Mechanism of CDI Development
- Clindamycin disrupts normal gut microbiota, creating conditions favorable for C. difficile proliferation and toxin production 3, 4
- Even topical clindamycin formulations carry CDI risk due to systemic absorption 3
- C. difficile produces toxins A and B that act as glucosyltransferases, disrupting colonocyte cytoskeleton and causing cell death 4
Risk Timeline and Monitoring
- CDI risk increases 7-10 fold during and in the first month after clindamycin exposure 4
- CDAD has been reported to occur over two months after clindamycin administration 1
- Patients should be monitored for diarrhea, fever, abdominal pain, and distension during and after clindamycin therapy 4
High-Risk Patient Populations
- Patients with history of antibiotic-associated colitis or inflammatory bowel disease require closer monitoring 3
- Concomitant use of other antibiotics or proton pump inhibitors further increases CDI risk 3