Clinical Use and Adverse Drug Reactions of Linezolid: A Retrospective Study in Four Belgian Hospital Centers

Thirot, Hélène; Briquet, Caroline; Frippiat, Frédéric; Jacobs, Frédérique; Holemans, Xavier; Henrard, Séverine; Tulkens, Paul M.; Spinewine, Anne; Bambeke, Françoise Van

doi:10.3390/antibiotics10050530

Cited by 26 publications

(23 citation statements)

References 39 publications

(89 reference statements)

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“…Studies on the risk factors of LZD-associated thrombocytopenia suggest a relationship with renal function. 25,[28][29][30][31]36 In this study, S cr , CL cr , and LZD clearance values were also shown to be significant factors in the univariate analysis. However, we did not include them in the multivariate analysis as they were confounding factors associated with the safety target achievement rate calculated using parameters A and B.…”

Section: Discussionsupporting

confidence: 55%

“…This suggests that they are a risk factor for thrombocytopenia in patients undergoing LZD therapy (Tables 3 and 4). Studies on the risk factors of LZD‐associated thrombocytopenia suggest a relationship with renal function 25,28–31,36 . In this study, S cr , CL cr , and LZD clearance values were also shown to be significant factors in the univariate analysis.…”

Section: Discussionsupporting

confidence: 52%

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Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Onita

Ishihara

Ikebuchi

et al. 2022

Clinical Pharmacy Therapeu

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What Is Known and Objective Linezolid (LZD) may cause thrombocytopenia, which can result in discontinuation of treatment. In this study, the blood LZD trough concentration was estimated based on population pharmacokinetic (PK) parameters derived from two previously published models in the Japanese population to determine the rate of achieving the target trough value when the risk of thrombocytopenia is low and to clarify its relationship with the onset of thrombocytopenia. Methods This study included adult patients hospitalized at Shimane University Hospital, who received LZD treatment for at least 4 days from January 2010 to December 2017. Patients whose platelet count fell below 70% before LZD administration were categorized as the thrombocytopenic group. Patient PK parameters were calculated based on the population PK models described by Matsumoto et al. and Sasaki et al., and these parameters were designated A and B, respectively. Based on these parameters, the rate of achieving an LZD trough concentration of less than 8 μg/ml, which is the safety target achievement rate, was calculated using a random simulation for each patient. We further analysed the association between the incidence of thrombocytopenia and patient factors, including safety target achievement rate, through univariate, multivariate, and receiver operating characteristic (ROC) analyses. Results and Discussion Patients (n = 77) aged 72 ± 11 years and weighing 56.7 ± 10.9 kg, with a creatinine clearance (CLcr) of 60.5 ± 47.2 ml/min and a cirrhosis prevalence of 9.1%, were analysed. All patients received LZD at a dose of 600 mg twice daily for a total of 10.9 ± 8.9 days. Univariate analyses revealed significant differences (p < 0.05) in the duration of LZD therapy, serum creatinine, creatinine clearance, LZD clearance, and the safety target achievement rate for parameters A and B between the thrombocytopenic and non‐thrombocytopenic groups. A multivariate analysis of these factors stratified with the cutoff values obtained by ROC analysis revealed that the duration of LZD therapy and the safety target achievement rates for parameters A and B were significant factors (odds ratios for duration of LZD therapy: 7.436 [95% confidence interval (CI): 1.918–28.831] and 4.712 [95% CI: 1.567–14.163]; odds ratio for safety target achievement rate: 0.060 [95% CI: 0.016–0.232] and 0.167 [95% CI: 0.056–0.498] for parameters A and B, respectively). When the safety target achievement rates for patients treated with LZD were compared between the thrombocytopenic and non‐thrombocytopenic groups, the safety target achievement rate was higher in the non‐thrombocytopenic group in both the patients treated with LZD for less than 10 days and those for 10 days or more. Therefore, the safety target achievement rate estimated by the PK/PD simulation may represent to be an important index for risk assessment of LZD‐induced thrombocytopenia. What Is New and Conclusion The risk of LZD‐induced thrombocytopenia, which increased with the duration of LZD therapy, may ...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionsupporting

confidence: 52%

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Onita

Ishihara

Ikebuchi

et al. 2022

Clinical Pharmacy Therapeu

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“…A few studies have reported some risk factors in patients treated with linezolid for thrombocytopenia, such as poorer renal function, longer treatment duration, and the coexisting condition of malignancy. [8][9][10] Most studies conducted to date concerning this issue have always focused on adult populations, with only a few demonstrating the impact of linezolid use on the development of thrombocytopenia in pediatric patients. [11,12] Therefore, we conducted this study to investigate the relationship between linezolid use and severe thrombocytopenia and identify the potential risk factors for severe linezolid-associated thrombocytopenia in pediatric patients.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and risk factors for severe linezolid-associated thrombocytopenia in pediatric patients: An analysis of a public database

et al. 2023

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Linezolid is widely used in various clinical settings. Studies have revealed that it may cause thrombocytopenia in adults. However, the correlation between the use of linezolid and thrombocytopenia in pediatric patients is still unclear. This study aimed to identify the impact of Linezolid on the occurrence of thrombocytopenia in children. A retrospective observational study was conducted using data on patients treated with linezolid from the Pediatric Intensive Care clinical database. Univariate and multiple logistic regression analyses were performed to identify the risk factors of linezolid-related severe thrombocytopenia. A total of 134 patients were included. The prevalence of severe thrombocytopenia was 8.96% (12/134). Univariate analysis indicated that the severe thrombocytopenia group showed significantly higher proportion of concomitant carbapenem (75% vs 44.3%; P < .05) and piperacillin/tazobactam (25% vs 6.6%; P < .05) than that of the non-severe thrombocytopenia group. Multivariate analysis also revealed that the occurrence of severe thrombocytopenia was significantly associated with concurrent use of carbapenem (odd ratio = 4.058; 95% confidence interval: 1.012-16.274; P = .048) and piperacillin/tazobactam (odd ratio = 5.335; 95% confidence interval: 1.117-25.478; P = .036). 75% of patients (9/12) developed severe thrombocytopenia within the first 7 days of linezolid use. The concomitant use of carbapenem and piperacillin/tazobactam was associated with an increased probability of severe thrombocytopenia in pediatric patients undergoing linezolid treatment. Further prospective clinical studies are required, and more detailed mechanisms of blood toxicity in pediatric patients must be investigated.

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“…A recent meta-analysis of randomized clinical trials showed that the efficacy of linezolid for treatment of Gram-positive bacterial pneumonia was comparable to that of controls [ 2 ]. Linezolid-associated nephrotoxic effects are lower than those of vancomycin; however, with widespread clinical uses of linezolid, there are concerns about its platelet suppression effects, anemia induction, and other hematologic adverse effects [ 3 – 6 ]. Due to differences in design protocols and anemia definitions among studies, incidences of reported linezolid-associated adverse events have been shown to range from 14.1% to 64.7% [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Linezolid-associated nephrotoxic e ects are lower than those of vancomycin; however, with widespread clinical uses of linezolid, there are concerns about its platelet suppression e ects, anemia induction, and other hematologic adverse e ects [3][4][5][6]. Due to di erences in design protocols and anemia de nitions among studies, incidences of reported linezolid-associated adverse events have been shown to range from 14.1% to 64.7% [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Identifying and Targeting Prediction of the PI3K-AKT Signaling Pathway in Drug-Induced Thrombocytopenia in Infected Patients Receiving Linezolid Therapy: A Network Pharmacology-Based Analysis

Xie

Chen

et al. 2022

Journal of Healthcare Engineering

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The pharmacological mechanisms underlying the adverse effects of linezolid on thrombocytopenia have not been conclusively determined. This network pharmacology study aimed at investigating the potential pharmacological mechanisms of linezolid-induced adverse reactions in thrombocytopenia. In this study, target genes for linezolid and thrombocytopenia were compared and analyzed. Overlapping thrombocytopenia-associated targets and predicted targets of linezolid were imported to establish protein-protein interaction networks. Gene Ontology and the Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were performed to determine the enriched biological terms and pathways. The mechanisms involved in linezolid-induced thrombocytopenia were established to be associated with various biological processes, including T cell activation, peptidyl serine modification, and peptidyl serine phosphorylation. The top five relevant protein targets were obtained, including ALB, AKT1, EGFR, IL6, and MTOR. Enrichment analysis showed that the targets of linezolid were positively correlated with T cell activation responses. The mechanism of action of linezolid was positively correlated with the PI3K-AKT signaling pathway and negatively correlated with the Ras signaling pathway. We identified the important protein targets and signaling pathways involved in linezolid-induced thrombocytopenia in anti-infection therapy, providing new information for subsequent studies on the pathogenesis of drug-induced thrombocytopenia and potential therapeutic strategies for rational use of linezolid in clinical settings.

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Clinical Use and Adverse Drug Reactions of Linezolid: A Retrospective Study in Four Belgian Hospital Centers

Cited by 26 publications

References 39 publications

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

Prevalence and risk factors for severe linezolid-associated thrombocytopenia in pediatric patients: An analysis of a public database

Identifying and Targeting Prediction of the PI3K-AKT Signaling Pathway in Drug-Induced Thrombocytopenia in Infected Patients Receiving Linezolid Therapy: A Network Pharmacology-Based Analysis

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