Digestive Diseases and Sciences

, Volume 50, Issue 10, pp 1785–1790

Acute Liver Failure Due To Amoxicillin and Amoxicillin/Clavulanate

  • Robert J. Fontana
  • A. Obaid Shakil
  • Joel K. Greenson
  • Ian Boyd
  • William M. Lee
Article

Abstract

The aim of our study is to report upon the presentation of two patients with life-threatening acute liver failure (ALF) due to amoxicillin and amoxicillin/clavulanate. A 59-year-old, Caucasian male presented with ALF 34 days after receiving amoxicillin/clavulanate. Despite aggressive supportive care, he died on hospital day 10. A 42-year-old, Caucasian female presented with ALF 21 days after receiving amoxicillin. She underwent successful liver transplantation on hospital day 19. In both cases, all competing causes of ALF had been excluded, liver pathology was consistent with drug-induced hepatitis, and cases were deemed “definite/highly probable” using causality assessment. Amongst 14 prior ALF/death cases due to amoxicillin/clavulanate, the mean age (62 years), male predominance (57%), and mean delay from drug cessation to presentation (17 days) is similar to what has been reported in patients with self-limited cholestatic hepatitis. Acute liver failure is a rare manifestation of amoxicillin and amoxicillin/clavulanate hepatotoxicity with no obvious clinical features at presentation portending a poor prognosis. Early transfer of patients with severe drug-induced hepatotoxicity (i.e., encephalopathy or coagulopathy) to a transplant center is recommended due to their poor likelihood of recovery.

Key Words

amoxicillin/clavulanate acute liver failure transplantation hepatotoxicity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bolzan H, Spatola J, Castelletto R, Curciarello J: Intrahepatic cholestasis induced by amoxicillin alone. Gastroenterol Hepatol 23:237–239, 2000PubMedGoogle Scholar
  2. 2.
    Rodriguez LA, Stricker BH, Zimmerman HJ: Risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid. Arch Intern Med 156:1327–1332, 1996CrossRefPubMedGoogle Scholar
  3. 3.
    Larrey D, Vial T, Micaleff A, Babany G, Morichau-Beauchant M, Michel H, Benhamou JP: Hepatitis associated with amoxicillin-clavulanic acid combination report of 15 cases. Gut 33:368–371, 1992PubMedGoogle Scholar
  4. 4.
    Brown SJ, Desmond PV: Hepatotoxicity of antimicrobial agents. Semin Liver Dis 22:157–167, 2002CrossRefPubMedGoogle Scholar
  5. 5.
    Hautekeete ML, Brenard R, Horsmans Y, Henrion J, Verbist L, Derue G, Druez P, Omar M, Kockx M, Hubens H: Liver injury related to amoxicillin-clavulanic acid: interlobular bile-duct lesion and extrahepatic manifestations. J Hepatol 22:71–77, 1995CrossRefGoogle Scholar
  6. 6.
    Higgins PR, Fontana RJ: Liver Transplantation in Acute Liver Failure. Panminerva Med 45:85–94, 2003PubMedGoogle Scholar
  7. 7.
    Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, McCashland TM, Shakil AO, Hay JE, Hynan L, Crippin JS, Blei AT, Samuel G, Reisch J, Lee WM, U.S. Acute Liver Failure Study Group: Results of a prospective study of Acute Liver Failure at 17 Tertiary Care Centers in the United States. Ann Intern Med 137:947–954, 2002PubMedGoogle Scholar
  8. 8.
    Criteria of drug induced liver disorders. Report of an international consensus meeting. J Hepatol 11:272–276, 1990Google Scholar
  9. 9.
    Maria VAJ, Victorino RMM: Development and validation of a clinical scale for the diagnosis of drug induced hepatitis. Hepatology 26:664–669, 1997PubMedGoogle Scholar
  10. 10.
    Danan G, Benichou C: Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: Application to drug-induced liver injuries. J Clin Epidemiol 46:1331–1336, 1993CrossRefPubMedGoogle Scholar
  11. 11.
    Benichou, C Danan G. Flahault A: Causality assessment of adverse reaction to drug-II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 46:1323–1330, 1993CrossRefPubMedGoogle Scholar
  12. 12.
    Aithal GP, Rawlins MD, Day CP: Clinical Diagnostic scale: a useful tool in the evaluation of suspected hepatotoxic adverse drug reactions. J Hepatol 33:949–952, 2000CrossRefPubMedGoogle Scholar
  13. 13.
    Lucena M, Camargo R, Andrade RJ, Perez-Sanchez CJ, Sanchez De La Cuesta F: Comparison of two clinical scales for causality assessment in hepatotoxicity. Hepatology 33:123–130, 2001CrossRefPubMedGoogle Scholar
  14. 14.
    http://Drugtopics.com website: Top 200 drugs in 2002. Accessed October 13, 2003.
  15. 15.
    Gresser U: Amoxicillin-clavulinic acid therapy may be associated with severe side effects: Review of the literature. Eur J Med Res 6:139–149, 2001PubMedGoogle Scholar
  16. 16.
    Limauro DL, Chan-Tompkins NH, Carter RW, Brodmerkel GJ, Jr, Agrawal RM: Amoxicillin/clavulanate associated hepatic failure with progression to Stevens–Johnson syndrome. Ann Pharmacother 33:560–564, 1999CrossRefPubMedGoogle Scholar
  17. 17.
    Ferrando-Vela J, Sanz-Moncasi P, Sevilla-Redondo G, Figueras Villalba P, Martin Algora I: Hepatic failure secondary to hepatitis due to amoxicillin-clavulanic acid. Treatment with corticoids. Ann Med Intern 19(10):551–552, 2002Google Scholar
  18. 18.
    Ersoz G, Karasu Z, Yildiz C, Akarca US, Yuce G, Batur Y: Severe toxic hepatitis associated with amoxicillin and clavulanic acid. J Clin Pharm Ther 26:225–229, 2001CrossRefPubMedGoogle Scholar
  19. 19.
    Hebbard GS, Smith KG, Gibson PR, Bhathal PS: Augmentin induced jaundice with a fatal outcome. Med J Aust 156:285–228, 1992PubMedGoogle Scholar
  20. 20.
    O'Donohue J. Oien KA, Donaldson P, Underhill J, Clare M, MacSween RN, Mills PR: Co-amoxiclav jaundice: clinical and histological features and HLA class II associations. Gut 47:717–720, 2000CrossRefPubMedGoogle Scholar
  21. 21.
    Australian Adverse Drug Reactions Bulletin 15:6–7, 1996Google Scholar
  22. 22.
    Shakil AO, Kramer d, Mazariegos GV, Fung JJ, Rakela J: Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria. Liver Trans 6:163–169, 2000Google Scholar
  23. 23.
    Larrey D: Epidemiology and individual susceptibility to adverse drug reactions affecting the liver. Semin Liver Dis 22:145–155, 2002CrossRefPubMedGoogle Scholar
  24. 24.
    Zimmerman HJ: Vulnerability of the liver to toxic injury. In Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia, Lippincott, Williams, and Wilkins 1999Google Scholar
  25. 25.
    Van der Auwerea P, Legrand JC. Ticarcillin clavulanic acid therapy in severe infections. Drugs Exp Clin Res Suppl 11:805–813, 1985Google Scholar
  26. 26.
    Reed MD. The clinical pharmacology of amoxicillin and clavulanic acid. Pediatr Infect Dis J 17:957–962, 1989Google Scholar
  27. 27.
    Dinis PB, Monteiro MC, Martins ML, Silva N, Gomes A. Sinus tissue pharmacokinetics after oral administration of amoxicillin/clavulanate acid. Laryngoscope 110:1050–1056, 2000PubMedGoogle Scholar
  28. 28.
    Hautekeete ML, Horsmans Y, Van Waeyenberge C, Demanet C, Henrion J, Verbist L, Brenard R, Sempoux C, Michielsen PP, Yap PS, Rahier J, Geubel AP. HLA association of amoxicillin-clavulanate induced hepatitis. Gastroenterology 117:1181–1186, 1999PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Robert J. Fontana
    • 1
    • 6
  • A. Obaid Shakil
    • 2
  • Joel K. Greenson
    • 3
  • Ian Boyd
    • 4
  • William M. Lee
    • 5
  1. 1.Department of Internal MedicineUniversity of Michigan Medical CenterAnn ArborUSA
  2. 2.Department of MedicineUniversity of PittsburghPittsburgh
  3. 3.Department of PathologyUniversity of Michigan Medical CenterAnn ArborUSA
  4. 4.Adverse Drug Reactions UnitTherapeutic Goods AdministrationCanberraAustralia
  5. 5.Department of MedicineUniversity of Texas SouthwesternDallasUSA
  6. 6.Ann ArborUSA

Personalised recommendations