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

Linezolid 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.

A 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.

A 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.

These 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.