1887
Volume 2022, Issue 3
  • ISSN: 0253-8253
  • EISSN: 2227-0426

Abstract

Introduction: Ceftriaxone, a third-generation cephalosporin, is frequently used for the treatment of various bacterial infections as a broad-spectrum antibiotic for many decades. Although ceftriaxone is a well-tolerated drug in most cases, it can lead to serious liver injury, which can be a real challenge to the treating physician. Given the potentially serious adverse effects that can vary from mild biochemical abnormalities to complete liver failure, we intend to assess the spectrum of liver injury based on biochemical criteria for patients treated with ceftriaxone for common bacterial infections in Qatar.Objectives: This study aimed to explore the incidence of ceftriaxone-induced liver injury at Hazm Mebaireek General Hospital, Qatar, and to evaluate the relationship of the ceftriaxone dose, if any, with liver dysfunction.Methods: This retrospective study included hospitalized adult patients treated with ceftriaxone at our hospital from January 2019 to December 2019 and analyzed demographic and clinical data obtained from electronic medical records. This study determined the incidence of liver injury (primary outcome) in patients treated with ceftriaxone (2 g/day) for ≥ 2 consecutive days by reviewing liver function test results until the day of discharge and at the first outpatient follow-up.

Results: The final data analysis included a total of 634 patients admitted and treated with ceftriaxone from January 2019 to December 2019.In the multivariate analysis with propensity score adjustment, ceftriaxone was independently associated with liver injury, especially when combined with other agents utilizing hepatic metabolism.Conclusions: Ceftriaxone was associated with a significantly higher incidence of liver injury (19.7%) when used along with other medications that are metabolized in the liver, as found in the present study compared with other similar studies (approximately 2.9%–13.9%). Furthermore, the incidence was too high to be ignored in clinical practice.

Loading

Article metrics loading...

/content/journals/10.5339/qmj.2022.27
2022-07-07
2022-09-29
Loading full text...

Full text loading...

/deliver/fulltext/qmj/2022/3/qmj.2022.27.html?itemId=/content/journals/10.5339/qmj.2022.27&mimeType=html&fmt=ahah

References

  1. Chitturi S, Farrell GC. Drug-induced cholestasis. Semin Gastrointest Dis 2001 Apr; 12:(2):113–24. PMID: 11352118.
    [Google Scholar]
  2. Padda MS, Sanchez M, Akhtar AJ, Boyer JL. Drug-induced cholestasis. Hepatology 2011 Apr; 53:(4):1377–87. PMID: 21480339.
    [Google Scholar]
  3. Sandrasegaran K, Alazmi WM, Tann M, Fogel EL, McHenry L, Lehman GA. Chemotherapy-induced sclerosing cholangitis. Clin Radiol 2006 Aug; 61:(8):670–8. PMID: 16843750.
    [Google Scholar]
  4. Lammert C, Bjornsson E, Niklasson A, Chalasani N. Oral medications with significant hepatic metabolism at higher risk for hepatic adverse events. Hepatology 2010 Feb; 51:(2):615–20. PMID: 19839004.
    [Google Scholar]
  5. Antoine DJ, Williams DP, Park BK. Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the science. Expert Opin Drug Metab Toxicol 2008 Nov; 4:(11):1415–27. PMID: 18950283.
    [Google Scholar]
  6. Park BK, Kitteringham NR, Maggs JL, Pirmohamed M, Williams DP. The role of metabolic activation in drug-induced hepatotoxicity. Annu Rev Pharmacol Toxicol 2005:45:177–202. PMID: 15822174.
    [Google Scholar]
  7. Smith DA, Schmid EF. Drug withdrawals and the lessons within. Curr Opin Drug Discov Devel 2006 Jan; 9:(1):38–46. PMID: 16445116.
    [Google Scholar]
  8. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR, Practice Parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2021 May 1; 116:(5):878–98. PMID: 33929376.
    [Google Scholar]
  9. Sgro C, Clinard F, Ouazir K, Chanay H, Allard C, Guilleminet C, et al. Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology 2002 Aug; 36:(2):451–5. PMID: 12143055.
    [Google Scholar]
  10. Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005 Aug; 129:(2):512–21. Erratum in: Gastroenterology 2005 Nov;129(2):512–21. PMID: 16083708.
    [Google Scholar]
  11. Russo MW, Hoofnagle JH, Gu J, Fontana RJ, Barnhart H, Kleiner DE, et al. Spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network. Hepatology 2014 Aug; 60:(2):679–86. Epub 13 May 2014. PMID: 24700436.
    [Google Scholar]
  12. Guidance for industry. Drug-induced liver injury: premarketing clinical evaluation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and Research (CBER). Drug Saf. Available online https://www.fda.gov/media/116737/downloadLast accessed 13 Aug 2021 Jul 2009.
    [Google Scholar]
  13. Manns MP, Obermayer-Straub P. Viral induction of autoimmunity: mechanisms and examples in hepatology. J Viral Hepat 1997; 4;:Suppl 2:42–7. PMID: 9429209.
    [Google Scholar]
  14. Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf 2007; 30:(4):277–94. PMID: 17408305.
    [Google Scholar]
  15. Amacher DE, Chalasani N. Drug-induced hepatic steatosis. Semin Liver Dis 2014 May; 34:(2):205–14. PMID: 24879984.
    [Google Scholar]
  16. Lucena MI, Andrade RJ, Kaplowitz N, García-Cortes M, Fernández MC, Romero-Gomez M, et al. Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex. Hepatology 2009 Jun; 49:(6):2001–9. PMID: 19475693.
    [Google Scholar]
  17. Lammert C, Einarsson S, Saha C, Niklasson A, Bjornsson E, Chalasani N. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: search for signals. Hepatology 2008 Jun; 47:(6):2003–9. PMID: 18454504.
    [Google Scholar]
  18. Castiella A, Zapata E, Lucena MI, Andrade RJ. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease. World J Hepatol 2014 Apr 27; 6:(4):160–8. PMID: 24799984.
    [Google Scholar]
  19. Yeong TT, Lim KH, Goubet S, Parnell N, Verma S. Natural history and outcomes in drug-induced autoimmune hepatitis. Hepatol Res 2016 Mar; 46:(3):E79–88. doi: 10.1111/hepr.12532. Epub 25 May 2015. PMID: 25943838.
    [Google Scholar]
  20. Wong WM, Wu PC, Yuen MF, Cheng CC, Yew WW, Wong PC, et al. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection. Hepatology 2000 Jan; 31:(1):201–6. PMID: 10613746.
    [Google Scholar]
  21. Verma S, Kaplowitz N. Chapter 27. Hepatotoxicity of antitubercular drugs. edited by: Neil Kaplowitz, Laurie D. DeLeve. Drug-Induced Liver Disease (Third Edition), Academic Press, 2013, Pages 483–504, ISBN 9780123878175. Available online https://www.sciencedirect.com/.
    [Google Scholar]
  22. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, et al. HLA-b*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009 Jul; 41:(7):816–9. PMID: 19483685.
    [Google Scholar]
  23. El Sherrif Y, Potts JR, Howard MR, Barnardo A, Cairns S, Knisely AS, Verma S. Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1/ABCB11 mutations? Liver Int 2013 Sep; 33:(8):1266–70. PMID: 23750872.
    [Google Scholar]
  24. Chen M, Borlak J, Tong W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury. Hepatology 2013 Jul; 58:(1):388–96. PMID: 23258593.
    [Google Scholar]
  25. Fontana RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology 2014 Apr; 146:(4):914–28. PMID: 24389305.
    [Google Scholar]
  26. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology 2014 Oct; 60:(4):1399–408. PMID: 25043597.
    [Google Scholar]
  27. Hillman L, Gottfried M, Whitsett M, Rakela J, Schilsky M, Lee WM, et al. Clinical features and outcomes of complementary and alternative medicine induced acute liver failure and injury. Am J Gastroenterol 2016 Jul; 111:(7):958–65. Erratum in: Am J Gastroenterol 2016 Oct;111(10):1504. PMID: 27694861.
    [Google Scholar]
  28. Zaki SA, Shanbag P. Biliary pseudolithiasis secondary to ceftriaxone therapy. Indian J Pharmacol 2010 Jun; 42:(3):193–4. PMID: 20871775.
    [Google Scholar]
  29. 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 1993 Nov; 46:(11):1323–30. PMID: 8229110.
    [Google Scholar]
  30. Shiffman ML, Keith FB, Moore EW. Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. Gastroenterology 1990; 99:(6)[Editor2];99:1772–8. PMID: 2227290.
    [Google Scholar]
  31. Soysal A, Eraşov K, Akpinar I, Bakir M. Biliary precipitation during ceftriaxone therapy: frequency and risk factors. Turk J Pediatr 2007 Oct-Dec; 49:(4):404–7. PMID: 18246742.
    [Google Scholar]
  32. Weaver RJ, Blomme EA, Chadwick AE, Copple IM, Gerets HHJ, Goldring CE, et al. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models. Nat Rev Drug Discov 2020; 19:(2):131–48. PMID: 31748707.
    [Google Scholar]
  33. De Valle MB, Av Klinteberg V, Alem N, Olsson R, Björnsson E. Drug-induced liver injury in a Swedish University hospital out-patient hepatology clinic. Aliment Pharmacol Ther 2006 Oct 15; 24:(8):1187–95. PMID: 17014577.
    [Google Scholar]
  34. de Abajo FJ, Montero D, Madurga M, García Rodríguez LA. Acute and clinically relevant drug-induced liver injury: a population-based case-control study. Br J Clin Pharmacol 2004 Jul; 58:(1):71–80. PMID: 15206996.
    [Google Scholar]
  35. Ghabril M, Chalasani N, Björnsson E. Drug-induced liver injury: a clinical update. Curr Opin Gastroenterol 2010 May; 26:(3):222–6. PMID: 20186054.
    [Google Scholar]
  36. Andrade RJ, Tulkens PM. Hepatic safety of antibiotics used in primary care. J Antimicrob Chemother 2011 Jul; 66:(7):1431–46. PMID: 21586591.
    [Google Scholar]
  37. Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH et al. Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist 2018 Oct 10;:11:1645–58. PMID: 30349322.
    [Google Scholar]
  38. Kaplowitz N. Drug-induced liver injury. Clin Infect Dis 2004 Mar 1; 38;: Suppl 2: S44–8. PMID: 14986274.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/qmj.2022.27
Loading
/content/journals/10.5339/qmj.2022.27
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error