Hyperbilirubinemia during quinupristin-dalfopristin therapy in liver transplant recipients: Correlation with available liver biopsy results

Study Objective. To review the liver histopathology in transplant recipient s who developed hyperbilirubinemia during therapy with quinupristin-dalfopr istin, a new streptogramin antibiotic, and to ascertain whether objective h istologic evidence of adverse drug effect could be correlated to serum bili rubin levels. Design. Retrospective analysis. Setting. University of Pittsburgh Medical Center. Patients. From a database of 34 liver recipients who received quinupristin- dalfopristin for vancomycin-resistant Enterococcus faecium infection who we re prospectively enrolled in a multicenter, open-label, emergency-use proto col, the data for a subset of 25 patients who underwent one or more liver b iopsies during therapy were reviewed for this study. Interventions. Quinupristin-dalfopristin was administered intravenously at 7.5 mg/kg every 8 hours. Available serum bilirubin levels from before, duri ng, and 1 week after therapy were tabulated. Liver biopsy results obtained within 1 week before and during therapy were retrospectively reviewed. Hist opathologic results were characterized and correlated to bilirubin level. Measurements and Main Results. Cholestatic changes were already present in 15 of 17 patients who underwent biopsy before therapy. During therapy, the most common findings from 40 biopsies (25 patients) were cholestasis (33 bi opsies), acute rejection (10), and periportal inflammation (8). There was n o evidence of drug-specific histopathologic injury. Conclusion. Hyperbilirubinemia in these patients was likely multifactorial and most frequently due to sepsis and prior graft injury.