An Unlikely Culprit: Novel Case of Vancomycin Oral Solution-Induced Agranulocytosis

Vancomycin is a glycopeptide antibiotic commonly used for the treatment of Clostridioides difficile colitis and other severe Gram-positive infections. While hematologic toxicities such as neutropenia and agranulocytosis are rare, they are typically associated with intravenous administration. We report the first known case of agranulocytosis secondary to oral vancomycin solution. A 44-year-old African American woman with a history of hypertension and prior alcohol use presented with severe diarrhea, palpitations, and hypokalemia after completing six days of oral vancomycin tablets. On admission, she was transitioned to vancomycin oral solution 125 mg four times daily. Her absolute neutrophil count (ANC) was 1.76 × 10⁹/L on admission and declined to 1.03 by hospital day 5. Extensive workup excluded nutritional deficiencies, viral infections, and concomitant medications as alternative causes. Colonoscopy demonstrated erythematous mucosa and chronic inflammation in the sigmoid colon, suggesting increased systemic absorption of oral vancomycin. The drug was discontinued and replaced with fidaxomicin, leading to normalization of ANC and resolution of diarrhea. This case underscores the importance of vigilance for hematologic complications even with oral vancomycin, particularly in patients with intestinal inflammation. Early recognition, discontinuation of vancomycin, and substitution with alternative therapy are key to recovery.