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

Choi, Go; Lee, Ju‐Yeun; Chang, Min Jung; Kim, Young Kyung; Cho, Yoonsook; Yu, Yun Mi; Lee, Euni

doi:10.1111/bcpt.13123

Cited by 43 publications

(71 citation statements)

References 24 publications

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“…41 Linezolid-associated thrombocytopenia was observed in 2.4% of clinical trial participants 42 ; however, postmarketing studies have since reported higher rates, ranging from 17.6% up to 48.4%. [43][44][45][46] Among cancer patients, specifically, linezolid-associated thrombocytopenia occurred in 14.1% to 34.1% of patients. 46,47 Linezolid is generally well tolerated even with higher dosing if duration is maintained at 7 days or less.…”

Section: Linezolid In Perspectivementioning

confidence: 99%

Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin

Lee

Seddon

et al. 2020

Ann Pharmacother

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Objective: To review the current literature describing pharmacology, pharmacokinetics/pharmacodynamics (PK/PD), efficacy, and safety of linezolid and daptomycin for the treatment of central nervous system (CNS) infections caused by vancomycin-resistant Enterococcus (VRE) faecium. Data Sources: A literature search of PubMed/MEDLINE databases was conducted (from 1950 to April 2020) utilizing the following key terms: vancomycin-resistant Enterococcus, VRE, meningitis, ventriculitis, CNS infection, daptomycin, and linezolid. Study Selection and Data Extraction: All relevant studies and case reports describing the treatment of VRE faecium from the CNS with linezolid or daptomycin were included. Data Synthesis: A total of 17 reports describing 22 cases were identified. There were 15 of 19 cases involving linezolid that reported clinical cure, of which 53.3% were monotherapy. Only 5 of 9 cases involving intravenous (IV) daptomycin resulted in cure; all 4 cases reporting daptomycin administration via the intrathecal or intraventricular route achieved clearance from the cerebrospinal fluid (CSF). Relevance to Patient Care and Clinical Practice: The preferred treatment option for VRE faecium infections involving the CNS remains unclear. Supporting evidence through observational case reports have described varying outcomes with linezolid and daptomycin. This review compares reported outcomes between the 2 agents and provides a thorough discussion on drug- and patient-specific variables to consider. Conclusions: Linezolid monotherapy appears to be safe and effective for the treatment of susceptible-VRE faecium CNS infections, with consideration of therapeutic drug monitoring in special populations and with prolonged treatment duration. Daptomycin is an effective treatment option via intrathecal or intraventricular administration when neurosurgical access is available. The role of IV daptomycin remains inconclusive.

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Section: Linezolid In Perspectivementioning

confidence: 99%

Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin

Lee

Seddon

et al. 2020

Ann Pharmacother

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“…One study [9] showed that carbapenem combination therapy and low baseline platelet count were signi cant predictors, and the duration of linezolid administration or renal function had little effect. However, a study conducted by Choi et al [11] revealed that low-dose aspirin was a possible risk factor, and the effect of carbapenem combination therapy was not signi cant.…”

Section: Introductionmentioning

confidence: 96%

“…Although under longer treatment durations, linezolid-treated patients had a higher potential for lower platelet counts compared to the comparator, the difference was not statistically signi cant. However, emerging observational studies have demonstrated the thrombocytopenic effect of linezolid [4][5][6][7][8][9][10][11][12][13]. Depending on different de nitions of thrombocytopenia, the incidence of thrombocytopenia ranged from 16.7-48.4% in adults treated with intravenous or oral linezolid [4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Although several studies have highlighted the susceptible population of linezolid-associated thrombocytopenia, the results are inconclusive. Possible risk factors including high daily dose per kg [4,6], long duration [5,8,11,13], renal impairment [5][6][7][8][10][11][12][13], and low baseline platelet counts [9,11,12] have been reported. One study [9] showed that carbapenem combination therapy and low baseline platelet count were signi cant predictors, and the duration of linezolid administration or renal function had little effect.…”

Section: Introductionmentioning

confidence: 99%

“…Multiple factors predispose an individual to platelet de ciency, including sepsis, major trauma, and drug exposure [14][15][16]. Medications that may induce thrombocytopenia are as follows: abciximab [15], amiodarone [11], aspirin [11,15], clopidogrel [15], digoxin [11], dipyridamole [15], epti batide [15], uconazole [17], haloperidol [11], heparin [11,[14][15][16], oxaliplatin [16], piperacillin [11,16], rifampin [11,16], ticlopidine [15], trimethoprim-sulfamethoxazole [11,15,16], valproic acid [11,15], and vancomycin [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Renal Replacement Therapy and Concurrent Fluconazole Therapy Increase Linezolid-Related Thrombocytopenia Among Adult Patients

Hsu

Chen

Hung

et al. 2021

Preprint

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Background: Linezolid, an antibiotic used against gram-positive pathogens, has been reported to be associated with thrombocytopenia. However, limited information is available on susceptibility to thrombocytopenia after linezolid usage. We aimed to investigate the risk factors for linezolid-associated thrombocytopenia. Methods: We conducted a retrospective cohort study of patients aged ≥ 18 years who received linezolid for ≥ 5 d during hospitalization in 2019. Demographic information, hospitalized information and laboratory data were extracted from electronic medical records. Thrombocytopenia was defined as a platelet count of <100,000 cells/mm3 or a reduction from baseline ≥ 25%. Binary logistic regression and survival analyses were used to evaluate the risk factors for linezolid-associated thrombocytopenia.Results: A total of 98 patients were enrolled. Thrombocytopenia occurred in 52 patients (53.1%), with a median first presentation 9 d after initiation of linezolid. There was no significant difference in the mortality or proportion of platelet transfusions between patients with and without thrombocytopenia. A higher risk of linezolid-associated thrombocytopenia was found in patients who received renal replacement therapy (RRT) (OR 4.8 [1.4-16.4]), concurrent fluconazole (OR 3.5 [1.2-9.8]), or a longer duration of linezolid treatment (OR 1.1 [1.0-1.1]). Patients who received RRT or concurrent fluconazole therapy had a shorter median time to develop thrombocytopenia (with vs. without RRT: 8 vs. 15 d; with vs. without fluconazole: 11 vs. 15 d). Those who simultaneously received RRT and fluconazole had the shortest median of time (6.5 d) and the highest risk of developing thrombocytopenia (87.5%).Conclusions: Patients who received RRT, concurrent fluconazole treatment, or a longer-duration linezolid had a higher risk of developing linezolid-associated thrombocytopenia.

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Predictive Modeling of Drug‐Related Adverse Events with Real‐World Data: A Case Study of Linezolid Hematologic Outcomes

Patel,

Doernberg,

Zack

et al. 2024

Clin Pharma and Therapeutics

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Electronic health records (EHRs) provide meaningful knowledge of drug‐related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de‐identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post‐treatment. Random forest classification (RFC) was used for AE prediction, and reduced feature models were evaluated using cumulative importance (cImp) for feature selection. Grade 3+ thrombocytopenia and anemia occurred in 31% of 2,171 and 56% of 2,170 evaluable patients, respectively. Of the total 53 features, as few as 7 contributed at least 50% cImp, resulting in prediction accuracies of 70% or higher and area under the receiver operating characteristic curves of 0.886 for grade 3+ thrombocytopenia and 0.759 for grade 3+ anemia. Sensitivity analyses in strictly defined patient subgroups revealed similarly high predictive performance in full and reduced feature models. A logistic regression model with the same 50% cImp features showed similar predictive performance as RFC and good concordance with RFC probability predictions after isotonic calibration, adding interpretability. Collectively, this work demonstrates potential for machine learning prediction of AE risk in real‐world patients using few variables regularly available in EHRs, which may aid in clinical decision making and/or monitoring.

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

Cited by 43 publications

References 24 publications

Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin

Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin

Renal Replacement Therapy and Concurrent Fluconazole Therapy Increase Linezolid-Related Thrombocytopenia Among Adult Patients

Predictive Modeling of Drug‐Related Adverse Events with Real‐World Data: A Case Study of Linezolid Hematologic Outcomes

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