A 32-year-old woman with community-acquired pneumonia caused by Streptococcus pneumoniae is started on azithromycin. On day 3 of therapy, she develops severe nausea, vomiting, and abdominal cramping. Stool culture grows Clostridioides difficile toxin-positive. What is the most appropriate next step in management?

Explanation

## Management of Antibiotic-Associated C. difficile Infection (CDI) ### Immediate Action **Key Point:** The offending antibiotic must be discontinued immediately when CDI is diagnosed, unless the underlying infection is life-threatening and no alternative exists. ### Why Azithromycin Must Stop Macrolides, including azithromycin, are well-established risk factors for CDI because they disrupt normal colonic flora and allow *Clostridioides difficile* overgrowth. Continuing the agent perpetuates the pathogenic environment. ### Treatment of CDI | Severity | First-line Agent | Dosing | |----------|------------------|--------| | Mild-moderate | Vancomycin (oral) OR Fidaxomicin | 125 mg PO QID × 10 days | | Severe | Fidaxomicin preferred | 200 mg PO BID × 10 days | | Fulminant | Vancomycin + IV metronidazole | High-dose regimens | **High-Yield:** Metronidazole is NO LONGER recommended as monotherapy for CDI (2021 IDSA/SHEA guidelines); oral vancomycin or fidaxomicin are preferred because they achieve higher colonic concentrations. ### Alternative for Pneumonia Once CDI is confirmed, switch the pneumonia coverage to a non-macrolide agent (e.g., beta-lactam, fluoroquinolone, or respiratory fluoroquinolone if susceptibilities permit). **Clinical Pearl:** Antimotility agents (loperamide) are contraindicated in CDI as they increase risk of toxic megacolon and worsen outcomes. [cite:Harrison 21e Ch 157]