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

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 (C(min)) 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), C(min) (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 C(min) ≥ 2 mg/L, the probability of bacterial eradication was more than 80%; when C(min) ≥ 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 C(min) between 2 and 6.3 mg/L over time may be helpful in retaining appropriate efficacy and reducing the associated thrombocytopenia.

Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis

“…This could be attributed to thrombocytopenia being defined differently in the various RCTs. Although there was no statistically significant difference between linezolid and vancomycin with respect to thrombocytopenia, attention should still be paid to some risk factors for thrombocytopenia while using linezolid [32]. Nephrotoxicity is the most common adverse event associated with vancomycin use.…”

Nonclinical and Pharmacokinetic Assessments To Evaluate the Potential of Tedizolid and Linezolid To Affect Mitochondrial Function

“…Several groups of researchers have suggested the trough concentration (within certain ranges) as the exposure measure that best predicts the safety of oxazolidinones (44)(45)(46)(47)(48). The hypothesis that plasma trough levels above the MPS IC 50 of an oxazolidinone will result in permanently inhibited MPS was first advanced by Garrabou et al (12).…”

Risk factors for linezolid-associated thrombocytopenia in adult patients

“…Nukui et al [32] reported that high plasma LZD trough concentration is a risk factor for TP. Dong et al [7] reported the minimum trough level ( C min ) of linezolid was significantly higher in patients with TP than in those without TP (8.81 mg/L [1.98–37.54] vs. 2.88 mg/L [0.35–8.78], P  < 0.0001). Matsumoto et al [34] reported that the trough concentration of LZD [mg/L] was 14.4–35.6 versus (vs.) 6.9–7.2 and the area under the plasma linezolid concentration–time curve for 24 h (AUC24 h) [mg h/L] was 513.1–994.6 vs. 294.3–323.6 in the thrombocytopenic vs. non-thrombocytopenic patients.…”

“…Thrombocytopenia (TP) is a common adverse effect in adult patients and the prevalence has been reported about 15–50 % with different definitions [5–9]. Prolonged treatment duration [9, 10], renal insufficiencies [1, 2, 9, 11–13], chronic liver disease [11], malignancy [14], previous vancomycin use [15], baseline platelet count [16], and lower BW [7, 8, 17] have been reported as possible risk factors for LZD-associated TP. However, most of previous studies have been conducted in Western patients with relatively heavy BW.…”