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Published in: European Journal of Clinical Microbiology & Infectious Diseases 6/2014

01-06-2014 | Article

Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients

Authors: H.-Y. Dong, J. Xie, L.-H. Chen, T.-T. Wang, Y.-R. Zhao, Y.-L. Dong

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 6/2014

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Abstract

To investigate the risk factors associated with the development of thrombocytopenia, and define the thresholds of efficacy and safety in critically ill patients who received linezolid therapy. A retrospective study was performed in critically ill patients treated with linezolid. Risk factors associated with thrombocytopenia were identified via medical records and trough levels (Cmin) measured during linezolid treatment. By establishing a logistic model, the risks were predicted by the receiver operating characteristic (ROC) curve and the thresholds of efficacy and safety were identified in the patients. Logistic analysis showed that, weight (OR = 0.906; 95 % CI, 0.839–0.978; P = 0.011), baseline platelet count (OR = 0.989; 95 % CI, 0.977–1.000; P = 0.049), Cmin (OR = 1.545; 95 % CI, 1.203–1.983; P = 0.001), and APACHE II score (OR = 1.130; 95 % CI, 1.003–1.273; P = 0.044) were significant factors for linezolid-associated thrombocytopenia. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was the maximum, the best optimal cut-off point was 205.6 on the ROC curve; when Cmin ≥ 2 mg/L, the probability of bacterial eradication was more than 80 %; when Cmin ≥ 6.3 mg/L, the probability of thrombocytopenia was more than 50 %. In clinical practice, when the calculating results of the combined predictor ≤205.6, the risk of the development of thrombocytopenia may be higher. Furthermore, maintenance of Cmin between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.
Literature
1.
go back to reference Ament PW, Jamshed N, Horne JP (2002) Linezolid: its role in the treatment of gram-positive, drug-resistant bacterial infections. Am Fam Physician 65(4):663–670PubMed Ament PW, Jamshed N, Horne JP (2002) Linezolid: its role in the treatment of gram-positive, drug-resistant bacterial infections. Am Fam Physician 65(4):663–670PubMed
4.
go back to reference Gerson SL, Kaplan SL, Bruss JB, Le V, Arellano FM, Hafkin B, Kuter DJ (2002) Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 46(8):2723–2726PubMedCentralPubMedCrossRef Gerson SL, Kaplan SL, Bruss JB, Le V, Arellano FM, Hafkin B, Kuter DJ (2002) Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 46(8):2723–2726PubMedCentralPubMedCrossRef
5.
go back to reference Antal EJ, Hendershot PE, Batts DH, Sheu WP, Hopkins NK, Donaldson KM (2001) Linezolid, a novel oxazolidinone antibiotic: assessment of monoamine oxidase inhibition using pressor response to oral tyramine. J Clin Pharmacol 41(5):552–562PubMedCrossRef Antal EJ, Hendershot PE, Batts DH, Sheu WP, Hopkins NK, Donaldson KM (2001) Linezolid, a novel oxazolidinone antibiotic: assessment of monoamine oxidase inhibition using pressor response to oral tyramine. J Clin Pharmacol 41(5):552–562PubMedCrossRef
8.
go back to reference Thallinger C, Buerger C, Plock N, Kljucar S, Wuenscher S, Sauermann R, Kloft C, Joukhadar C (2008) Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother 61(1):173–176. doi:10.1093/jac/dkm431 PubMedCrossRef Thallinger C, Buerger C, Plock N, Kljucar S, Wuenscher S, Sauermann R, Kloft C, Joukhadar C (2008) Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother 61(1):173–176. doi:10.​1093/​jac/​dkm431 PubMedCrossRef
11.
go back to reference Tsuji Y, Hiraki Y, Matsumoto K, Mizoguchi A, Kobayashi T, Sadoh S, Morita K, Kamimura H, Karube Y (2011) Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction. J Infect Chemother 17(1):70–75. doi:10.1007/s10156-010-0080-6 PubMed Tsuji Y, Hiraki Y, Matsumoto K, Mizoguchi A, Kobayashi T, Sadoh S, Morita K, Kamimura H, Karube Y (2011) Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction. J Infect Chemother 17(1):70–75. doi:10.​1007/​s10156-010-0080-6 PubMed
12.
13.
go back to reference Hiraki Y, Tsuji Y, Hiraike M, Misumi N, Matsumoto K, Morita K, Kamimura H, Karube Y (2012) Correlation between serum linezolid concentration and the development of thrombocytopenia. Scand J Infect Dis 44(1):60–64. doi:10.3109/00365548.2011.608712 PubMed Hiraki Y, Tsuji Y, Hiraike M, Misumi N, Matsumoto K, Morita K, Kamimura H, Karube Y (2012) Correlation between serum linezolid concentration and the development of thrombocytopenia. Scand J Infect Dis 44(1):60–64. doi:10.​3109/​00365548.​2011.​608712 PubMed
15.
go back to reference Soriano A, Ortega M, Garcia S, Penarroja G, Bove A, Marcos M, Martinez JC, Martinez JA, Mensa J (2007) Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid. Antimicrob Agents Chemother 51(7):2559–2563. doi:10.1128/AAC.00247-07 PubMedCentralPubMedCrossRef Soriano A, Ortega M, Garcia S, Penarroja G, Bove A, Marcos M, Martinez JC, Martinez JA, Mensa J (2007) Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid. Antimicrob Agents Chemother 51(7):2559–2563. doi:10.​1128/​AAC.​00247-07 PubMedCentralPubMedCrossRef
16.
go back to reference Grau S, Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Alvarez-Lerma F (2005) Linezolid: low pre-treatment platelet values could increase the risk of thrombocytopenia. J Antimicrob Chemother 56(2):440–441. doi:10.1093/jac/dki202 PubMedCrossRef Grau S, Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Alvarez-Lerma F (2005) Linezolid: low pre-treatment platelet values could increase the risk of thrombocytopenia. J Antimicrob Chemother 56(2):440–441. doi:10.​1093/​jac/​dki202 PubMedCrossRef
18.
go back to reference Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41PubMed Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41PubMed
19.
go back to reference Niwa T, Suzuki A, Sakakibara S, Kasahara S, Yasuda M, Fukao A, Matsuura K, Goto C, Murakami N, Itoh Y (2009) Retrospective cohort chart review study of factors associated with the development of thrombocytopenia in adult Japanese patients who received intravenous linezolid therapy. Clin Ther 31(10):2126–2133. doi:10.1016/j.clinthera.2009.10.017 PubMedCrossRef Niwa T, Suzuki A, Sakakibara S, Kasahara S, Yasuda M, Fukao A, Matsuura K, Goto C, Murakami N, Itoh Y (2009) Retrospective cohort chart review study of factors associated with the development of thrombocytopenia in adult Japanese patients who received intravenous linezolid therapy. Clin Ther 31(10):2126–2133. doi:10.​1016/​j.​clinthera.​2009.​10.​017 PubMedCrossRef
20.
go back to reference Wu VC, Wang YT, Wang CY, Tsai IJ, Wu KD, Hwang JJ, Hsueh PR (2006) High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease. Clin Infect Dis 42(1):66–72. doi:10.1086/498509 PubMedCrossRef Wu VC, Wang YT, Wang CY, Tsai IJ, Wu KD, Hwang JJ, Hsueh PR (2006) High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease. Clin Infect Dis 42(1):66–72. doi:10.​1086/​498509 PubMedCrossRef
21.
go back to reference Rayner CR, Forrest A, Meagher AK, Birmingham MC, Schentag JJ (2003) Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. Clin Pharmacokinet 42(15):1411–1423PubMedCrossRef Rayner CR, Forrest A, Meagher AK, Birmingham MC, Schentag JJ (2003) Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. Clin Pharmacokinet 42(15):1411–1423PubMedCrossRef
22.
23.
go back to reference Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M (2012) Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother 67(8):2034–2042. doi:10.1093/jac/dks153 PubMedCrossRef Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M (2012) Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother 67(8):2034–2042. doi:10.​1093/​jac/​dks153 PubMedCrossRef
Metadata
Title
Therapeutic drug monitoring and receiver operating characteristic curve prediction may reduce the development of linezolid-associated thrombocytopenia in critically ill patients
Authors
H.-Y. Dong
J. Xie
L.-H. Chen
T.-T. Wang
Y.-R. Zhao
Y.-L. Dong
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 6/2014
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-013-2041-3

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