Study design and recruitment criteria
This was a retrospective study involving linezolid-administered (orally or intravenously) elderly patients at Zhongshan Hospital, Fudan University. This study was performed between January 2015 and April 2021. Clinical data for these patients were collected from the medical records, with permission from the Ethical Committee of the ZhongShan Hospital. Patients who were ≥ 65 years and had been administered with linezolid at a standard dose of 600 mg, q 12h for three or more days were recruited. While those diagnosed with hematological diseases (haemato-oncologic disease, myelosuppression, and disseminated intravascular coagulation), bleeding, with less than three times of monitoring on platelet counts, receiving radiotherapy or chemotherapy, who lacked baseline platelet counts, who had baseline platelet counts less than 100×109·L-1 or receiving blood transfusions 2 weeks before the initiation of linezolid therapy, were excluded from the study.
Definition of thrombocytopenia
Platelet counts were used to categorize the included patients into two groups: the linezolid-induced thrombocytopenia (LI-TP) group and the no development of thrombocytopenia (NO-TP) group. Thrombocytopenia was defined as a reduction in platelet counts to levels below 100×109·L-1.
Clinical and demographic characteristics
We collected the following clinical and demographic characteristics for each elderly patient: age, gender, weight, payment method (self-payment and medical insurance), hospitalized department (medical, surgical, and ICU), laboratory variables [baseline platelet counts, hemoglobin, total bilirubin, total albumin, serum albumin, alanine aminotransferase, aspartate aminotransferase, and estimated glomerular filtration rate (eGFR)], as well as concomitant disease [hypertension, diabetes, chronic heart disease (CHD), chronic obstructive pulmonary disease (COPD), and cancer]. Other records were also extracted, if the patients were transferred to ICU, had surgery, mechanical ventilation, renal replacement therapy or bleeding. Moreover, we comprehensively analyzed variables associated with linezolid treatment and combined medications, including duration of linezolid therapy, concomitance with antibiotics (carbapenems, quinolones, aminoglycosides, cephalosporin, piperacillin-tazobactam (PTZ), macrolides, compound sulfamethoxazole), vasoactive drugs [nitrates, β-blockers, dihydropyridines, angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEI)], anticoagulant agents (heparin, warfarin), antiplatelet agents (aspirin, clopidogrel), azole antifungal agents, nonsteroidal anti-inflammatory drugs (NSAIDS), spironolactone, hydrochlorothiazide, furosemide, proton-pump inhibitors (PPI), polyene phosphatidylcholine, glutathione, ursodeoxycholic acid, magnesium isoglycyrrhizinate (MGL), benzodiazepines, opioid agonist, tamsulosin, β2-agonist, theophylline, rifampin, and isoniazid.
The statistical analysis was carried out using SPSS version 23.0 (IBM, 187 Chicago, IL, USA). The Kolmogorov-Smirnov test was performed to evaluate whether the data were normally or non-normally distributed. Normally distributed continuous variables were described as the mean ± standard deviation (SD), and the student’s t-test was used to compare the LI-TP group and NO-TP group. Non-normally distributed continuous variables were expressed as the median (interquartile range, IQR), and groups were compared using the Mann-Whitney U-test. Chi-squared test or Fisher’s exact test were used to analyze the categorical variables which were described as numbers (percentages). Furthermore, multivariate logistic regression analysis was used to determine the association between the independent variables and linezolid-induced thrombocytopenia. A risk predictive model was constructed according to the variables retained in the final model. A risk score was developed according to the regression coefficient. To evaluate the discrimination of the risk model, receiver operating characteristic (ROC) curves were constructed, and area under the curve (AUC) was calculated. The goodness of fit was assessed with the Hosmer-Lemeshow test. All P values were two-sided, and a P value of less than 0.05 was considered significant.