Pharmacokinetics and Pharmacodynamics of Vancomycin in Severe COVID-19 Patients: a Preliminary Study in a Chinese Tertiary Hospital (preprint)

ABSTRACT

Vancomycin plays an important role in the treatment of concurrent infections in severe coronavirus disease 2019 (COVID-19) patients. However, few is known about its pharmacokinetics (PK) in these patients. Here we performed therapeutic drug monitoring (TDM) of intravenous vancomycin with or without nasal administration in these patients. Drug dosage was adjusted depending on vancomycin concentration. A population PK model was developed using NONMEM software. Therapeutic effects, and vancomycin-related adverse events were monitored. A total of 63 samples from 8 patients were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The mean trough and peak concentration were 13.79±6.61 (4.63-34.2) mg/L (n=36) and 30.97±9.71 (17-49.9) mg/L (n=27), respectively. 25.4% of serum vancomycin concentration was beyond optimal range. Dose adjustments were made for 3 patients. The PK of vancomycin was consistent with two-compartment model, with the clearance and distribution volume in the central compartment of 4.3 L/h and 2.0 L, respectively. The AUC0-24/MIC of vancomycin was 848±566 h. Target infection was clinically cured in all patients, and no vancomycin-associated nephrotoxicity was detected during the TDM process. In conclusion, the PK studies of vancomycin in COVID-19 patients are needed to optimize drug dosage. Based on our PK model, the clearance of vancomycin was 4.3 L/h.