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.
Similar content being viewed by others
References
Parker RI (2012) Etiology and significance of thrombocytopenia in critically ill patients. Crit Care Clin 28:399–411
Loo AS, Gerzenhtein L, Ison MG (2012) Antimicrobial drug induced thrombocytopenia: a review of the literature. Semin Thromb Hemost 38:818–829
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
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
Bernstein WB, Trotta RF, Rector JT, Tjaden JA, Barile AJ (2003) Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 37(4):517–520
Green SL, Maddox JC, Huttenbach ED (2001) Linezolid and reversibile myelosuppression. JAMA 285:1291
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
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
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
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
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
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
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
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
Brier ME, Stalker DJ, Aronoff GR et al (2003) Pharmacokinetics of linezolid in subjects with renal dysfunction. Antimicrob Agents Chemother 47:2775–2780
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
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
Lin YH (2006) High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency. Int J Antimicrob Agents 28:345–351
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
Kuter DJ, Tillotson GS (2001) Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy 21:1010–1013
Attassi K, Hershberger E, Alam R, Zervos MJ (2002) Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 34:695–698
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
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
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
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
Phizer (2008) ZIVOX (linezolid) label information, 2008. Retrieved June 20
Hiraki Y et al (2012) Correlation between serum linezolid concentration and the development of thrombocytopenia. Scand J Infect Dis 44:60–64
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
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
Poulakos MN et al (2012) Probable linezolid-induced thrombocytopenia in a patient with vancomycin-resistant enterococci. J Pharm Pract 25(6):615–618
Lam S (2012) Linezolid-associated thrombocytopenia. Consult Pharm 27(7):504–508
Naranjo CA et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245
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
Corresponding author
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-013-1585-6