Flucloxacillin-associated hepatic injury

Authors

  • G. H. Koek,

    1. Department of Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium
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  • B. H. Ch. Stricker,

    Corresponding author
    1. Netherlands Center for Monitoring of Adverse Reactions to Drugs, Rijswijk, The Netherlands
    2. Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, The Netherlands
      Principal Medical Officer, Netherlands Centre for Monitoring of Adverse Reactions to Drugs, P. O. Box 5406, 2280 HK Rijswijk, The Netherlands.
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  • A. P. R. Blok,

    1. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
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  • S. W. Schalm,

    1. Department of Internal Medicine II, University Hospital Dijkzigt, Rotterdam, The Netherlands
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  • V. J. Desmet

    1. Department of Histopathology, University Hospital St Rafael, Leuven, Belgium.
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Principal Medical Officer, Netherlands Centre for Monitoring of Adverse Reactions to Drugs, P. O. Box 5406, 2280 HK Rijswijk, The Netherlands.

Abstract

Eleven cases of hepatic injury attributed to the intake of flucloxacillin were reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs between 1982 and 1992. They concerned four men and seven women, with a mean age of 57 years, treated for 2–28 days with an oral dose varying from 1500–4000 mg per day. Symptoms mostly appeared 10 to 30 days after starting treatment with flucloxacillin. Biochemically, the pattern was compatible with cholestatic hepatitis in seven cases, with a mixed cholestatic-hepatocellular type of injury in one case, a hepatocellular pattern in two cases, and mild liver enzyme elevations in one patient. Two patients died, one due to fatal bleeding from the liver after biopsy, and the second patient to a combination of hepatic and cardiac failure. The other patients recovered, on average 72 days after peaking of serum aminotransferase values. Histology in seven cases showed cholestatic hepatitis in five, with cholangitis or cholangiolitis in four of these patients. In the other two patients, there was centrilobular cholestasis with extensive bridging fibrosis and portal-central bridging necrosis, respectively.

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