Expert consensus statement on therapeutic drug monitoring and individualization of linezolid

Lin, Bin; Hu, Yangmin; Xu, Ping; Xu, Tao; Chen, Chunyan; He, Le; Zhou, Mi; Chen, Zhangzhang; Zhang, Chunhong; Yu, Xu-Ben; Fang, Luo; Zhu, Junfeng; Ji, Yanlan; Lin, Qun; Cao, Hengbin; Dai, Youqin; Lu, Xiaoyan; Shi, Changcheng; Li, Li; Wang, Changjiang; Li, Xumei; Fang, Qiongyan; Jin, Miao; Zhu, Zhengyi; Lin, Guangyong; Zhan, Haichao; Lv, Shi‐Wen; Zhu, Ying; Cai, Xinjun; Yin, Ying; Chen, Meng; Xu, Qian; Zhang, Yiwen; Xu, Yubin; Pea, Federico; Jiang, Saiping; Dai, Haibin

doi:10.3389/fpubh.2022.967311

Cited by 12 publications

(16 citation statements)

References 112 publications

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“…The ratio of the area under the drug plasma concentration–time curve over 24 h to the MIC (AUC/MIC) or percentage time above the MIC (%T > MIC) are predictors of the therapeutic response, and concentrations in the range of 2–8 mcg/mL appear to define the optimal window for acute bacterial infections, while a cut-off value >8 mg/L is an indicator for thrombocytopenia. Thus, TDM based on PK models or continuous infusion over 6 h instead of intermittent infusion is recommended for the optimization of Linezolid treatment to achieve the target AUC/MIC [ 17 , 36 , 37 , 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…There are multiple challenges in critically ill patients obtaining clinical and microbiological cures. These patients are more susceptible to being infected with multidrug-resistant or pan-drug-resistant pathogens, with limited therapeutic options and the necessity of choosing the rescue antibiotics (such as polymyxins or Linezolid) associated with a high degree of toxicity [ 36 , 42 ]. In addition, the substantial intra- or inter-individual variation in PK characteristics often leads to suboptimal or toxic therapeutic levels.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review

et al. 2023

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Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug–drug or drug–nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug–nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review

et al. 2023

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“…Studies have shown that a combination of linezolid and rifampicin can reduce the prevalence of thrombocytopenia and the hemoglobin level in patients (Legout et al, 2010). Reported high-risk factors of linezolid-induced thrombocytopenia and reduction in the hemoglobin level include low platelet count, low body weight, low level of albumin, old age, longer duration of medication, renal insufficiency, and C min >8 mg/L (Chen et al, 2012;Lin et al, 2022). Duration of linezolid therapy >14 days and renal insufficiency are independent high-risk factors of ADRs in the blood system (Hirano et al, 2014;Hanai et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Biological samples were stable within 24 h at room temperature, at two freeze-thaw cycles, and after freezing at −80 °C for 3 months. The C min range of linezolid is 2-8 mg/L, whereas the C max range is 12-26 mg/L (Beijin Chest Hospital and Antituberculosis, 2021;Lin et al, 2022).…”

Section: Determination Of Drug Concentration In Plasmamentioning

confidence: 99%

Evaluation of the impact of rifampicin on the plasma concentration of linezolid in tuberculosis co-infected patients

Yan,

Shi,

et al. 2023

Front. Pharmacol.

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Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07–26.06) vs. 13.18 (7.48–23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06–16.53) vs. 4.27 (0.45–10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.

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“…However, the dosing of anti-infectives is more difficult in intensive care unit (ICU) patients, as they have altered pharmacokinetics due to profoundly altered pathophysiological processes [ 3 , 4 ]. Routine therapeutic drug monitoring (TDM) of especially antibiotics in ICU patients is recommended to reduce the risk of under- or overdosing, to maximize the efficacy, and to minimize toxicity [ 5 – 7 ], hopefully leading to a higher rate of target attainment.…”

Section: Introductionmentioning

confidence: 99%

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

Rebholz,

Liebchen,

Paal

et al. 2024

ICMx

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Background Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). Methods Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. Results Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. Conclusions Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection “lung”. Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

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Expert consensus statement on therapeutic drug monitoring and individualization of linezolid

Cited by 12 publications

References 112 publications

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review

Evaluation of the impact of rifampicin on the plasma concentration of linezolid in tuberculosis co-infected patients

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

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