Therapeutic drug monitoring of linezolid and exploring optimal regimens and a toxicity-related nomogram in elderly patients: a multicentre, prospective, non-interventional study.

Abstract

The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear. In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed. A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36-72 h and 26.1 (17.0, 38.1) mg/L at 5-10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715-0.820), a sensitivity of 71.1% and a specificity of 73.2%. Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65-80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid. Clinical trial registration number: ChiCTR2100045707.