Retrospective analysis of the risk factors for linezolid-induced thrombocytopenia in adult Japanese patients

Hirano, Ryuichi; Sakamoto, Yuichi; Tachibana, Naoki; Ohnishi, Motoki

doi:10.1007/s11096-014-9961-6

Cited by 57 publications

(85 citation statements)

References 14 publications

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“…When patients were categorized into 3 groups using 2 cut-off values (17, 22 kg/mg/day) of dosage amount, the prevalence of thrombocytopenia in each groups was not significantly different (Reduction rate of >25%; <17 mg/kg/day (69.2%), 17 -22 mg/kg/day (69.2%), >22 mg/kg/day (75.9%), p = 0.90: Reduction rate of >50%; <17 mg/kg/day (38.5%), 17 -22 mg/kg/day (50.0%), >22 mg/kg/day (44.8%), p = 0.84). While prolonged treatment duration for more than 14 days has been reported as risk factors for linezolid-induced thrombocytopenia [7], the proportion of patients with thrombocytopenia did not show significant difference between patients with linezolid therapy for more than 14 days and patients with linezolid therapy for less than 13 days in our study (40.0% vs 45.3%, p = 0.87, Table 2). There were not significant differences in the body size descriptors between linezolid therapy for more than 14 days and for less than 13 days (Table 2).…”

Section: Resultscontrasting

confidence: 77%

“…Prolonged treatment duration [7], renal insufficiencies [8], chronic liver disease [8] and lower body weight [2] have been reported as possible risk factors for linezolid-induced thrombocytopenia. Additionally, Natsumoto et al showed that both higher daily dose (mg/kg/day) (prevalence of thrombocytopenia; <17 mg/kg/day (17%), 17 -22 mg/kg/day (34%), 22 -27 mg/kg/day (48%), >27 mg/kg/day (72%)) and elevated serum creatinine were significant risk factors for linezolid-induced thrombocytopenia in non-hemodialysis patients [9].…”

Section: Discussionmentioning

confidence: 99%

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Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Kato¹,

Hagihara²,

Yamagishi³

et al. 2016

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Previous study suggested that low body weight was one of the risk factors of thrombocytopenia induced by linezolid in non-hemodialysis patients. However, there have been little investigations for the linezolid-induced thrombocytopenia in hemodialysis patients. This study was to evaluate the association between several factors of body size descriptors and thrombocytopenia in hemodialysis-patients. No factor of body size descriptors showed significant correlation with linezolid-induced thrombocytopenia (patients with thrombocytopenia vs patients without thrombocytopenia: body

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Section: Resultscontrasting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Kato¹,

Hagihara²,

Yamagishi³

et al. 2016

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“…Indeed, reports soon emerged of increased thrombocytopenia in this population with multiple-dose administration (10,11). This finding has since been replicated in multiple observational studies, most of which have been conducted in Asian populations (12)(13)(14)(15)(16)(17)(18)(19).…”

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confidence: 86%

Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety

Crass

Cojutti

Pai

et al. 2019

Antimicrob Agents Chemother

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Linezolid is administered as a fixed dose to all patients despite evidence of increased exposure and myelosuppression in renal impairment. The objectives of these studies were to assess the risk of thrombocytopenia with standard-dose linezolid in renal impairment and to identify an alternate dosing strategy. In study 1, data from adult patients receiving linezolid for Ն10 days were retrospectively reviewed to determine the frequency of thrombocytopenia in patients with and without renal impairment. Time-to-event analyses were performed using Cox proportional-hazards models. In study 2, population pharmacokinetic modeling was employed to build covariatestructured models using an independent data set of linezolid concentrations obtained during routine therapeutic drug monitoring (TDM). Monte Carlo simulations were performed to identify linezolid dosing regimens that maximized attainment of therapeutic trough concentrations (2 to 8 mg/liter) across various renal-function groups. Toxicity analysis (study 1) included 341 patients, 133 (39.0%) with renal impairment. Thrombocytopenia occurred more frequently among patients with renal impairment (42.9% versus 16.8%; P Ͻ 0.001), and renal impairment was independently associated with this toxicity in multivariable analysis (adjusted hazard ratio [aHR], 2.37; 95% confidence interval [CI], 1.52 to 3.68). Pharmacokinetic analyses (study 2) included 1,309 linezolid concentrations from 603 adult patients. Age, body surface area, and estimated glomerular filtration rate (eGFR) were identified as covariates of linezolid clearance. Linezolid dose reductions improved the probability of achieving optimal exposures in simulated patients with eGFR values of Ͻ60 ml/min. Thrombocytopenia occurs more frequently in patients with renal impairment receiving standard linezolid doses. Linezolid dose reduction and trough-based TDM are predicted to mitigate this treatment-limiting toxicity.

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“…While establishing appropriate measures to improve clinical outcomes for the patients are essential tasks for clinicians, published studies reporting the incidence and predictive factors for linezolid‐induced thrombocytopenia had been insufficient and often limited due to the variabilities of the study design and patient population. Most studies included patients with haemato‐oncologic diseases without distinguishing subgroups or disease severity as the presence of haemato‐oncologic diseases or variable status of myelosuppression can be a significant confounder in the evaluation of thrombocytopenia. Moreover, a number of studies included patients with a baseline platelet count of <100 × 10 3 /mm 3 in their populations, indicating that these patients already had thrombocytopenia.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases

Choi

Lee

Chang

et al. 2018

Basic Clin Pharma Tox

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This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato-oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.4 (SD 15.8) years, thrombocytopenia occurred at a rate of 29.2% after an average of 11.2 (SD 7.4) days of the initiation of linezolid therapy. Significant predictive factors for thrombocytopenia included the duration of linezolid therapy longer than or equal to 7 days (adjusted odds ratios [ORs] 7.25, 19.51 and 28.80; 95% confidence intervals [CIs] 1.92-27.38, 4.76-79.95 and 6.48-127.92 for 7-13 days, 14-20 days and ≥21 days, respectively; P < 0.01 for all values), baseline platelet count <150 × 10 /mm (adjusted OR, 5.08; 95% CI, 2.06-12.55; P < 0.001), creatinine clearance <30 mL/min (adjusted OR, 4.19; 95% CI, 1.59-11.06; P = 0.004) and concurrent low-dose aspirin therapy (adjusted OR, 2.99; 95% CI, 1.26-7.08; P = 0.013). Baseline platelet count less than 150 × 10 /mm was an independent predictor of early-onset (≤6 days) thrombocytopenia (adjusted OR, 5.07; 95% CI, 1.46-17.58; P = 0.011). Closer monitoring of platelet count is required in patients who receive parenteral linezolid therapy for 7 days or more, and have low baseline platelet counts or impaired renal function.

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Retrospective analysis of the risk factors for linezolid-induced thrombocytopenia in adult Japanese patients

Abstract: Receiving linezolid therapy for ≥14 days and a low creatinine clearance rate were suggested to be risk factors for linezolid-induced thrombocytopenia. The platelet counts of patients with these risk factors should be closely monitored.

Cited by 57 publications

References 14 publications

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety

Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases

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