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. 2010 Apr 1;6(3):322–326. doi: 10.1007/s13181-010-0047-0

Severe Drug-induced Liver Injury Associated with Prolonged Use of Linezolid

Liesbet De Bus 1,✉, Pieter Depuydt 1,2, Louis Libbrecht 3, Linos Vandekerckhove 4, Joke Nollet 1, Dominique Benoit 1, Dirk Vogelaers 4, Hans Van Vlierberghe 5
PMCID: PMC3550492  PMID: 20358416

Abstract

This study aims to describe a patient developing concomitant severe liver failure and lactic acidosis after long-term treatment with linezolid. A 55-year-old Caucasian woman developed concomitant severe liver failure and lactic acidosis after a treatment with linezolid for 50 days because of infected hip prosthesis. Other causes of liver failure and lactic acidosis were excluded by extensive diagnostic workup. A liver biopsy showed microvesicular steatosis. As linezolid toxicity was considered to be the cause of the lactic acidosis and the severe hepatic failure, the antibiotic was withdrawn. After 4 days of supportive therapy and hemodialysis, the serum lactate level returned within normal limits. The prothrombin time ratio and thrombocytes recovered within 2 weeks. Bilirubin levels normalized within 14 weeks. Since no other cause could be identified, liver injury was considered to be drug-related. Resolution of the hepatotoxicity occurred after discontinuation of linezolid, supportive treatment measures, and hemodialysis. Both lactic acidosis and microvesicular steatosis after the use of linezolid are related to mitochondrial dysfunction. The Council for International Organizations of Medical Sciences/Roussel Ucalf Causality Assessment Method scale revealed that the adverse drug event was probable. Prolonged exposure to linezolid may induce severe hepatotoxicity. Clinicians should be aware of this possible adverse effect especially in case of long-term treatment.

Keywords: Linezolid, Liver failure, Microvesicular steatosis, Lactic acidosis

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Acknowledgments

Conflict of interest

The authors state that there are no potential conflicts of interest or funding.

Footnotes

The patient and relatives provided written informed consent for the publication of this case report.

References

  • 1.Falagas ME, Vardakas KZ. Benefit–risk assessment of linezolid for serious Gram-positive bacterial infections. Drug Saf. 2008;31:753–768. doi: 10.2165/00002018-200831090-00004. [DOI] [PubMed] [Google Scholar]
  • 2.Bishop E, Melvani S, Howden BP, Charles PGP, Grayson ML. Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: a proposed protocol for monitoring therapy in complex patients. Antimicrob Agents Chemother. 2006;50:1599–1602. doi: 10.1128/AAC.50.4.1599-1602.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Manfredi R. Update on the appropriate use of linezolid in clinical practice. Ther Clin Risk Manag. 2006;2:455–464. doi: 10.2147/tcrm.2006.2.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Vinh DC, Rubinstein E. Linezolid: a review of safety and tolerability. J Infect. 2009;59(S1):S59–S74. doi: 10.1016/S0163-4453(09)60009-8. [DOI] [PubMed] [Google Scholar]
  • 5.William ML. Drug-induced hepatotoxicity. N Engl J Med. 2003;349:474–485. doi: 10.1056/NEJMra021844. [DOI] [PubMed] [Google Scholar]
  • 6.Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf. 2007;30:277–294. doi: 10.2165/00002018-200730040-00001. [DOI] [PubMed] [Google Scholar]
  • 7.Lucena MI, Camargo R, Andrade RJ, et al. Comparison of two clinical scales for causality assessment in hepatotoxicity. Hepatology. 2001;33:123–130. doi: 10.1053/jhep.2001.20645. [DOI] [PubMed] [Google Scholar]
  • 8.Garcia-Cortés M, Lucena MI, Pachkoria K, et al. Evaluation of Naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury. Aliment Pharmacol Ther. 2008;27:780–789. doi: 10.1111/j.1365-2036.2008.03655.x. [DOI] [PubMed] [Google Scholar]
  • 9.Hussaini SH, Farrington EA. Idiosyncratic drug-induced liver injury: an overview. Expert Opin Drug Saf. 2007;6:673–684. doi: 10.1517/14740338.6.6.673. [DOI] [PubMed] [Google Scholar]
  • 10.Fromenty B, Pessayre D. Impaired mitochondrial function in microvesicular steatosis. J Hepatol. 1997;26:43–53. doi: 10.1016/s0168-8278(97)80496-5. [DOI] [PubMed] [Google Scholar]
  • 11.Fromenty B, Berson A, Pessayre D. Microvesicular steatosis and steatohepatitis: role of mitochondrial dysfunction and lipid peroxidation. J Hepatol. 1997;26:13–22. doi: 10.1016/s0168-8278(97)82328-8. [DOI] [PubMed] [Google Scholar]
  • 12.Labbe G, Pessayre D, Fromenty B. Drug-induced liver injury through mitochondrial dysfunction: mechanisms and detection during preclinical safety studies. Fundam Clin Pharmacol. 2008;22:335–353. doi: 10.1111/j.1472-8206.2008.00608.x. [DOI] [PubMed] [Google Scholar]
  • 13.McKee EE, Ferguson M, Bentley AT, Marks TA. Inhibition of mammalian mitochondrial protein synthesis. Antimicrob Agents Chemother. 2006;50:2042–2049. doi: 10.1128/AAC.01411-05. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.De Vriese AS, Van Coster A, Smet J, et al. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin Infect Dis. 2006;42:1111–1117. doi: 10.1086/501356. [DOI] [PubMed] [Google Scholar]
  • 15.Garrabou G, Soriano A, Lopez S, et al. Reversible inhibition of mitochondrial protein synthesis during linezolid-related hyperlactatemia. Antimicrob Agents Chemother. 2007;51:962–967. doi: 10.1128/AAC.01190-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Livermore DM. Quinupristin/dalfopristin and linezolid: where, when, which and whether to use? J Antimicrob Chemother. 2000;46:347–350. doi: 10.1093/jac/46.3.347. [DOI] [PubMed] [Google Scholar]
  • 17.McKee EE, Ferguson M, Bentley AT, et al. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006;50:2042–2049. doi: 10.1128/AAC.01411-05. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Brunt EM. Non alcoholic fatty liver disease. In: MacSween RNM, Burt AD, Portmann BC, Ferrell LD, editors. MacSween’s pathology of the liver. 5. Amsterdam: Elsevier Health Sciences; 2007. pp. 367–398. [Google Scholar]
  • 19.Ukleya A, Romano MM. Complications of parenteral nutrition. Gastroenterol Clin N Am. 2007;36:23–46. doi: 10.1016/j.gtc.2007.01.009. [DOI] [PubMed] [Google Scholar]
  • 20.Linden P. Safety profile of meropenem. Drug Saf. 2007;30(8):657–668. doi: 10.2165/00002018-200730080-00002. [DOI] [PubMed] [Google Scholar]

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