A 32-year-old woman with no significant past medical history presents with community-acquired pneumonia characterized by fever (38.5°C), productive cough, and hypoxia (SpO2 92% on room air). Chest X-ray demonstrates a left lower lobe consolidate. She is started on azithromycin 500 mg orally daily. On hospital day 3, she develops severe nausea, vomiting, and diffuse abdominal cramping. Vital signs are stable (BP 118/76 mmHg, HR 98 bpm, RR 18, T 37.2°C). Laboratory evaluation reveals AST 145 U/L (normal <40), ALT 168 U/L (normal <40), alkaline phosphatase 82 U/L (normal <120), total bilirubin 0.8 mg/dL (normal <1.2), and WBC 7,200/μL. Stool studies are negative for C. difficile toxins. Symptoms completely resolve within 48 hours of discontinuing azithromycin. Which of the following best explains the mechanism of this adverse drug reaction?

1. A)Idiosyncratic drug metabolism via CYP3A4 inhibition causing accumulation of a toxic metabolite
2. B)Acute cholestasis secondary to direct hepatocellular injury from macrolide ester hydrolysis
3. C)Pseudomembranous colitis from disruption of normal colonic flora
4. D)Drug-induced hepatotoxicity from macrolide metabolism via CYP3A4 with subsequent transaminitisGABARITO
5. E)Acute interstitial nephritis with secondary hyperammonemia and hepatic encephalopathy