Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: A prospective interventional study

Background: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR), daily dose with PK/PD indices. Methods: : This prospective interventional study was conducted in twoindependent intensive care units (ICUs) from February 2021 to January 2022.Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 hours to minimum inhibitory concentration(AUC 24 /MIC). Results: : Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.72% vs. 40.48%; P<0.001）or AUC 24 /MIC (53.19% vs. 23.81%; P = 0.005). There were no significant differences in clinical success (72.22% vs. 50.00%; P = 0.183) and microbiological success (83.33% vs. 75.00%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (8.70% vs. 7.14%; P> 0.999), and mortality between the two modalities was also not significant different (21.74% vs. 17.86%; P=0.728). Correlation analysis showed an inverse correlation of EFR with target concentration (r= -0.4057, P < 0.001) and AUC 24 /MIC (r= -0.4183, P < 0.001), whereas a significant positive association of daily dose was found with target concentration (r = 0.4962, P < 0.001) and AUC 24 /MIC (r = 0.6551, P < 0.001). Conclusion: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, an inverse correlation of PK/PD indices was found with EFR,and a positive association with daily dose. Trial registration: The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393)