Skip to main content
Log in

Linezolid-induced thrombocytopenia in impaired renal function: is it time for a dose adjustment? A case report and review of literature

  • Review Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Thrombocytopenia is a common complication in the intensive care unit (ICU), but the incidence of drug-induced thrombocytopenia (DIT) is not well defined. We investigate linezolid-induced thrombocytopenia in patients with impaired renal function. Since recent studies suggest that linezolid clearance is reduced in these patients and there are no precise data confirming that dose-adjustment should be required, we performed a systematic analysis in order to establish whether it is necessary to consider a dose adjustment and promote studies to confirm this concept.

Methods

We report a case of thrombocytopenia (nadir 32 × 103/μl) in a patient with acute kidney injury who was treated with linezolid for a MRSA pulmonary infection. We performed a systematic review of the literature through PubMed with the aim to include every case report, case series, prospective and retrospective clinical study reporting linezolid-induced thrombocytopenia with concomitant impaired renal function.

Results

An increasing number of clinical studies suggest a correlation between the onset of linezolid-induced thrombocytopenia and renal dysfunction. Close monitoring of platelet count and hemoglobin is recommended in patients treated with linezolid, especially in those with impaired renal function because the reduction of its clearance causes drug accumulation, as some studies have reported.

Conclusions

Clinicians should consider the potential risk of this complication, especially in elderly patients with end-stage renal disease. Further studies should be encouraged to determine if the incidence of linezolid-related thrombocytopenia could be reduced by a dose adjustment according to renal function, for which currently there is still no specific recommendation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Parker RI (2012) Etiology and significance of thrombocytopenia in critically ill patients. Crit Care Clin 28:399–411

    Article  PubMed  Google Scholar 

  2. Loo AS, Gerzenhtein L, Ison MG (2012) Antimicrobial drug induced thrombocytopenia: a review of the literature. Semin Thromb Hemost 38:818–829

    Article  CAS  PubMed  Google Scholar 

  3. Spellberg B, Yoo T, Bayer AS (2004) Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6. J Antimicrob Chemother 54:832–835

    Article  CAS  PubMed  Google Scholar 

  4. Plachouras D, Giannitsioti E, Athanassia S et al (2006) No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment. Clin Infect Dis 43:89–91

    Article  Google Scholar 

  5. Bernstein WB, Trotta RF, Rector JT, Tjaden JA, Barile AJ (2003) Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 37(4):517–520

    Article  PubMed  Google Scholar 

  6. Green SL, Maddox JC, Huttenbach ED (2001) Linezolid and reversibile myelosuppression. JAMA 285:1291

    Article  CAS  PubMed  Google Scholar 

  7. Patel N, VanDeWall H, Tristani L, Rivera A, Woo B, Dihmess A, Li HK, Smith R, Lodise TP (2012) A comparative evaluation of adverse platelet outcomes among Veterans’ Affairs patients receiving linezolid or vancomycin. J Antimicrob Chemother 67:727–735

    Article  CAS  PubMed  Google Scholar 

  8. Rao N, Ziran BH, Wagener MM et al (2004) Similar hematologic effects of long-term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections. Clin Infect Dis 38:1058–1064

    Article  CAS  PubMed  Google Scholar 

  9. Nasraway SA, Shorr AF, Kuter DJ et al (2003) Linezolid does not increase the risk of thrombocytopenia in patients with nosocomial pneumonia: comparative analysis of linezolid and vancomycin use. Clin Infect Dis 37:1609–1616

    Article  CAS  PubMed  Google Scholar 

  10. Kalil et al (2010) Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med 38(9):1802–1808

    Article  CAS  PubMed  Google Scholar 

  11. Krishnasam Z, Carlton D, Bimbo L et al (2002) Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution. Kidney Int 61:1136–1142

    Article  Google Scholar 

  12. Abe S, Chiba K, Cirincione B, Grasela TH, Ito K, Suwa T (2009) Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients. J Clin Pharmacol 49:1071–1078

    Article  CAS  PubMed  Google Scholar 

  13. Whitehouse T, Cepeda JA, Shulman R et al (2005) Pharmacokinetic studies. Of linezolid and teicoplan in the critically ill. J Antimicrob Chemother 55:333–340

    Article  CAS  PubMed  Google Scholar 

  14. Matsumoto K, Takeda Y, Takeshita A, Fukunaga N, Shigemi A, Yaji K et al (2009) Renal function as a predictor of linezolid-induced thrombocytopenia. Int J Antimicrob Agents 33:98–99

    Article  CAS  PubMed  Google Scholar 

  15. Brier ME, Stalker DJ, Aronoff GR et al (2003) Pharmacokinetics of linezolid in subjects with renal dysfunction. Antimicrob Agents Chemother 47:2775–2780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Fiaccadori E, Maggiore U, Rotelli C et al (2004) Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure. Crit Care Med 32:2437–2442

    Article  CAS  PubMed  Google Scholar 

  17. Tsuji Y, Hiraki Y, Mizoguchi A, Hayashi W, Kamohara R, Kamimura H et al (2008) Pharmacokinetics of repeated dosing of linezolid in a hemodialysis patient with chronic renal failure. J Infect Chemother 14:156–160

    Article  CAS  PubMed  Google Scholar 

  18. Lin YH (2006) High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency. Int J Antimicrob Agents 28:345–351

    Article  CAS  PubMed  Google Scholar 

  19. Wu VC et al (2006) High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease. Clin Infect Dis 42:66–72

    Article  PubMed  Google Scholar 

  20. Kuter DJ, Tillotson GS (2001) Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy 21:1010–1013

    Article  CAS  PubMed  Google Scholar 

  21. Attassi K, Hershberger E, Alam R, Zervos MJ (2002) Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 34:695–698

    Article  PubMed  Google Scholar 

  22. Sasaki et al (2011) Population pharmacokinetic and pharmacodynamic analysis of linezolid and a hematologic side effect, thrombocytopenia, in Japanese patients. Antimicrob Agents Chemother 55:1867–1873

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Matsumoto K et al (2010) Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction. Int J Antimicrob Agents 36:179–181

    Article  CAS  PubMed  Google Scholar 

  24. Tsuji Y et al (2011) Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction. J Infect Chemother 17:70–75

    Article  CAS  PubMed  Google Scholar 

  25. Hiraki Y et al (2011) Influence of linezolid clearance on the induction of thrombocytopenia and reduction of hemoglobin. Am J Med Sci 342:456–460

    Article  PubMed  Google Scholar 

  26. Phizer (2008) ZIVOX (linezolid) label information, 2008. Retrieved June 20

  27. Hiraki Y et al (2012) Correlation between serum linezolid concentration and the development of thrombocytopenia. Scand J Infect Dis 44:60–64

    Article  CAS  PubMed  Google Scholar 

  28. Nukui Y et al (2013) High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia. J Antimicrob Chemother 68(9):2128–2133

    Google Scholar 

  29. Taguchi K et al (2013) A reduced linezolid dosage maintains favorable efficacy with minimal hematologic toxicity in a methicillin-resistant Staphylococcus aureus-infected patient with renal insufficiency. Scand J Infect Dis 45:77–80

    Article  CAS  PubMed  Google Scholar 

  30. Poulakos MN et al (2012) Probable linezolid-induced thrombocytopenia in a patient with vancomycin-resistant enterococci. J Pharm Pract 25(6):615–618

    Article  PubMed  Google Scholar 

  31. Lam S (2012) Linezolid-associated thrombocytopenia. Consult Pharm 27(7):504–508

    Article  PubMed  Google Scholar 

  32. Naranjo CA et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

There is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. P. Cossu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cossu, A.P., Musu, M., Mura, P. et al. Linezolid-induced thrombocytopenia in impaired renal function: is it time for a dose adjustment? A case report and review of literature. Eur J Clin Pharmacol 70, 23–28 (2014). https://doi.org/10.1007/s00228-013-1585-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-013-1585-6

Keywords

Navigation