Acute Liver Injury Following Outpatient Trimethoprim‐Sulfamethoxazole Use for Small Intestinal Bacterial Overgrowth: A Case Report

ABSTRACT Drug‐induced liver injury (DILI) is a leading cause of acute liver failure in the United States and remains difficult to predict and diagnose. Trimethoprim‐sulfamethoxazole (TMP‐SMX) is widely prescribed and generally well tolerated, yet rare cases of severe idiosyncratic hepatotoxicity have been reported. We describe a 30‐year‐old woman who developed fever, malaise, leukopenia, and profound hepatocellular injury days after initiating TMP‐SMX and neomycin for small intestinal bacterial overgrowth. TMP‐SMX was discontinued, and treatment with N‐acetylcysteine (NAC) and supportive care was initiated. Liver enzymes, coagulopathy, and renal dysfunction steadily improved, and the patient was discharged on hospital day 6 with complete resolution of laboratory abnormalities within one month. In addition to highlighting another documented case of liver injury caused by TMP‐SMX, this case emphasizes the unpredictable nature of drug‐induced hepatotoxicity, the potential use of NAC in DILI, and reinforces the importance of early recognition, comprehensive evaluation, and prompt withdrawal of the offending agent. Clinicians should maintain vigilance when new constitutional or hepatic symptoms arise during therapy and should report suspected cases to improve collective understanding and patient safety data.