Development and validation of a risk prediction model for linezolid-induced thrombocytopenia in elderly patients

Abstract

ObjectivesLinezolid is the first oxazolidinone antimicrobial agent developed for treating multi-drug-resistant gram-positive bacterial infections. The study aimed to investigate the risk factors of linezolid (LI)-induced thrombocytopenia (LI-TP) and to develop and validate a risk prediction model to identify elderly patients at high risk of developing LI-TP during linezolid therapy.MethodsA retrospective cohort study was performed at Zhongshan Hospital, FuDan University, China. The study involved elderly Chinese patients aged ≥65 years administered with linezolid (600 mg) twice a day between January 2015 and April 2021. We collected the patients’ clinical characteristics and demographic data from electronic medical records, and compared the differences between LI-TP patients and those who had not developed thrombocytopenia (NO-TP) after linezolid treatment. The risk prediction model was developed based on the regression coefficient generated from logistic regression model.ResultsA total of 343 inpatients were enrolled from January 2015 to August 2020 and were used as the training set. Among them, 67 (19.5%) developed LI-TP. Multivariate logistic regression analysis revealed that baseline platelet counts <150×109·L-1 (odds ratio (OR)=3.576; p<0.001), age ≥75 years (OR=2.258; p=0.009), estimated glomerular filtration rate (eGFR <60 mL·(min·1.73 m2)-1 (OR=2.553; p=0.002), duration of linezolid therapy ≥10 d (OR=3.218; p<0.001), intensive care unit (ICU) admittance (OR=2.682; p=0.004), concomitant piperacillin-tazobactam (OR=3.863; p=0.006) were independent risk factors for LI-TP in elderly patients. The LI-TP risk prediction model was established using a scoring method based on the regression coefficient and exhibited a good discriminative power, with an area under the curve (AUC) of 0.795 (95% confidence interval (CI) 0.740 to 0.851) and 0.849 (95% CI 0.760 to 0.939) in the training set (n=343) and validation set (n=90) respectively.ConclusionsThese findings indicate that duration of linezolid therapy, age, eGFR, ICU admittance, baseline platelet counts, concomitant piperacillin-tazobactam were significantly associated with LI-TP in elderly patients. A risk prediction model based on these risk factors showed a good discriminative performance and may be useful for clinicians to identify patients at high risk of developing LI-TP.

Electronic health record-based prediction models for in-hospital adverse drug event diagnosis or prognosis: a systematic review

“…The included studies used various approaches to retrieve or generate ADE labels and could broadly be categorized into 3 categories: 5 category I studies using ADEs that were registered by healthcare providers (20%), 30 , 33 , 51–53 3 category II studies using adverse event signals followed by a(n) (formal) ADE causality assessment (12%), 43 , 44 , 46 and 15 category III studies using adverse event signals without a(n) (formal) ADE causality assessment (60%). 31 , 34–39 , 41 , 42 , 45 , 46 , 48–50 , 54 Studies in the first category retrieved International Classification of Diseases version 9 or 10 codes (ICD-9 or ICD-10) 55 , 56 that explicitly describe a causal relation between a drug and an adverse symptom (eg, ICD-10 code I95.1: Hypotension due to drugs ).…”

“…In 2 of these studies, formal ADE causality assessments using the Naranjo probability scale were applied. 43 , 44 Studies in the last category only retrieved adverse event signals without a subsequent (formal) ADE causality assessment. Various abnormal clinical findings were used as adverse event signals, among which: ICD-9 or ICD-10 codes that only described certain symptoms, abnormal lab values, abnormal electrocardiogram (ECG) findings, medication administrations combined with abnormal ECG findings, and medication administrations combined with mental status change assessments or skin and pain assessments.…”

A risk prediction model of linezolid-induced thrombocytopenia for elderly patients with chronic kidney disease is urgently needed

“…We read with interest the recently published article by Qin et al 1 The authors stated that a range of factors were risk factors of linezolid-induced thrombocytopenia (LI-TP) in elderly patients. These risk factors were estimated glomerular filtration rate (eGFR), being admitted to an intensive care unit (ICU), baseline platelet counts and concomitant piperacillin-tazobactam.…”

“…Renal function injury is associated with an increased risk of LI-TP 6. Qin et al showed that the LI-TP risk prediction model exhibited a good discriminative power in the training set and validation set,1 the model is useful for treatment planning of patients with chronic kidney disease because eGFR as an independent risk factor could influence LI-TP. As a screening tool, the LI-TP risk prediction model can display pertinent information to guide clinicians and clinical pharmacists thus avoiding thrombocytopenia, which can be a serious side effect.…”

“…Furthermore, working without the LI-TP risk prediction model tool could increase the workload of doctors but also lead to serious consequences, such as bleeding. The inspiring outcomes from the report by Qin et al 1 strongly help clinical pharmacists or doctors to provide better pharmaceutical care or medical technology for elderly patients at risk of LI-TP.…”