Abstract: AIM: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/pharmacodynamics (PK/PD) of daptomycin in critically ill patients.  METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition (PTA) and the cumulative fraction response (CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: Cmax were (85.5±25.4) μg/mL and (79.4±29.2) μg/mL, AUC0-24 were (674.2±267.2) mg·L-1·h and (952.9±304.5) mg·L-1·h，t1/2 were (10.9±2.1) h and (11.6±4.3) h，Vd were (0.21±0.12) L/kg and (0.150±0.061) L/kg，CL were (13.3±4.7) mL·h-1·kg-1 and (9.2±3.4) mL·h-1·kg-1. There were significant differences in AUC0-24 and CL between the two groups, and there was no significant difference in other pharmacokinetic parameters. Monte Carlo simulation results showed that when the sensitivity of MRSA to daptomycin decreased (MIC≥1 mg/L), the PTA values of ECMO group, non-ECMO group and healthy volunteers were less than 90%. CONCLUSION: ECMO may affect the PK/PD of daptomycin in patients with severe infection to a certain extent. When MIC≥1 mg/L, it is recommended to increase the dosage to achieve the expected antibacterial effect. In view of the individual differences of daptomycin in patients with ECMO, therapeutic drug monitoring (TDM) should be implemented in these patients, and the administration scheme should be adjusted according to the sensitivity of MRSA pathogens to drugs.

Key words: daptomycin, severe infection, the extracorporeal membrane oxygenation, the PK-PD study