Fosfomycin is an antibiotic often used to treat urinary tract infections (UTIs) with only rare transient hepatotoxicity. We present a case of fosfomycin-induced liver injury and describe the histopathologic findings on biopsy. A 64 year-old female patient with no prior liver disease or risk factors was started on fosfomycin as prophylaxis for recurrent UTIs. Within a week of her first dose she presented with fatigue, jaundice, and mixed liver enzyme elevation. Clinical workup for acute liver injury was unremarkable, and biopsy showed panacinar and portal necroinflammation with predominantly lymphocytic infiltrate and cholestasis. This was thought to be likely related to fosfomycin exposure. While liver enzymes trended down, bilirubin initially remained elevated. However, within three months the patient achieved clinical and biochemical recovery. Only two other reports of fosfomycin-induced liver injury requiring biopsy were found. Both developed acute cholestatic hepatitis within days of exposure, and subsequent biopsy similarly showed lymphocytic necroinflammation. Although one patient initially developed acute liver failure, both recovered fully within few months. Overall, these cases suggest likely an idiosyncratic or immune-mediated liver toxicity of fosfomycin which is typically self-limited with rapid recovery. Liver biopsy may be useful in confirming the diagnosis.

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One etiology is drug-induced liver injury. Cloxacillin, an anti-staphylococcal penicillin, typically causes “bland” cholestasis. We present the first case of cloxacillin-induced acute ductopenia or VBDS and a review of published cloxacillin-induced liver injuries. A 66-year-old woman with no prior liver disease, but known penicillin allergy, was treated for post-carotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a two-week history of weakness and jaundice. Laboratory work-up showed elevated liver enzymes, hyperbilirubinemia, and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation, and ductopenia with epithelial injury, but no ductular reaction. Two-months later, she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure four months later. Four additional articles were found with histopathologic descriptions of cloxacillin-related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10-60 days. Cloxacillin-induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described “bland” cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.