Objectives 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. Methods 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. Results 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. Conclusions 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.

A new lignan glycoside, tianshanoside A (1), together with a known phenylpropanoid glycoside, syringin (2) and two known lignan glycosides, picraquassioside C (3), and aketrilignoside B (4), were isolated from the whole plant of Viola tianshanica Maxim. The structure of the new compound was elucidated by extensive NMR (¹H, ¹³C, COSY, HSQC, HMBC and ROESY) and high resolution mass spectrometry analysis. The three lignans 1, 3, and 4 did not exhibit significant cytotoxicity against human gastric cancer Ags cells or HepG2 liver cancer cells. This is the first report of the isolation of a lignan skeleton from the genus Viola L.

Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aims to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from the PubMed and Embase. Model predictability was evaluated using prediction-based simulation-based and Bayesian forecasting based approach to assess the model predictability. Prediction-based diagnostics found that the prediction error within ±30% (F₃₀) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

Background Linezolid is often used for the infections caused by drug-resistant Gram-positive bacteria. Recent studies suggested that large between-subject variability (BSV) and within-subject variability could alter drug pharmacokinetics (PK) during linezolid therapy due to pathophysiological changes. Objective The review synthesized information on linezolid population PK studies and summarized the significant covariates that influence the PKs of linezolid. Methods A literature search was performed from PubMed, Web of Science, and Embase from their inception to 30 September 2021. Published studies were included if they contained data analyzing linezolid PK parameters in humans using a population approach with a nonlinear mixed-effects model. Results Twenty-five studies were included in adults and five studies in pediatric patients. One- and two-compartment models were the commonly used structural models for linezolid. Body size [weight, lean body weight, and body surface area], creatinine clearance (CLcr), and age significantly influenced linezolid PK. The median clearance (CL) values (range) in infants [0.128 L/h/kg (0.121-0.135)] and children [0.107 L/h/kg (0.088-0.151)] were higher than in adults [0.098 L/h/kg (0.044-0.237)]. For patients with severe renal impairment (CLcr ≤ 30 mL/min), the CL was 37.2% (15.2-55.3%) lower than in patients with normal renal function. Conclusion Linezolid’s optimal dosage could be adjusted based on the patient’s body size, renal function, and age. More studies are needed to explore the exact mechanism of elimination of linezolid and evaluate PK characteristics in pediatric patients.