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Controlled Clinical Trial
. 2022 Aug 2;22(1):667.
doi: 10.1186/s12879-022-07618-6.

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

Jinhui Xu #  1 , Lufen Duan #  1 , Jiahui Li  1 , Fang Chen  1 , Xiaowen Xu  2 , Jian Lu  3 , Zhiwei Zhuang  2 , Yifei Cao  3 , Yunlong Yuan  4 , Xin Liu  1 , Jiantong Sun  1 , Qin Zhou  1 , Lu Shi  5 , Lian Tang  6
Affiliations
Controlled Clinical Trial

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

Jinhui Xu et al. BMC Infect Dis. .

Abstract

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) with PK/PD indices.

Methods: This prospective interventional study was conducted in two independent 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 h to minimum inhibitory concentration (AUC24/MIC).

Results: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC24/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC24/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC24/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger.

Conclusion: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).

Keywords: Continuous infusion; Continuous venovenous hemofiltration; Intermittent infusion; Prospective interventional study; Vancomycin.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of participant selection. Study population selection and criteria for exclusion, a total of 51 patients were included in the analysis. CKRT, continuous kidney replacement therapy; CVVH, continuous venovenous hemofiltration; ICUs, intensive care units; ECMO, extracorporeal membrane oxygenation; IKRT, intermittent kidney replacement treatment
Fig. 2
Fig. 2
Scatter plot of observed vancomycin concentration in the II group (A) and CI group (B). Scatter plot of AUC24/MIC in the II group (C) and CI group (D). Solid line represents the mean ± SD. The gray area represents the target range
Fig. 3
Fig. 3
Target attainment of initial observed concentration (A) and overall observed concentration (B) in the II group and CI group. Target attainment of initial AUC24/MIC (C) and overall AUC24/MIC (D) in the II group and CI group during CVVHa. aFor target concentration, therapeutic exposure is defined as trough concentration of 15–25 mg/L for continuous infusion (CI group) and steady-state concentration of 10-20 mg/L for intermittent infusion group (II group), respectively. For AUC24/MIC target, therapeutic exposure is defined as 400–650 for both groups. Suptherapeutic exposure is defined as the target PK/PD indices above the desired range, whereas subtherapeutic exposure is defined as PK/PD indices below the desired range. *Bonferroni-adjusted P < 0.05
Fig. 4
Fig. 4
Correlation analysis of target PK/PD indices with EFR. Correlation of observed concentration with EFR in the II group (A) and CI group (B). Correlation of AUC24/MIC with EFR in the II group (C) and CI group (D). The Spearman correlation coefficient r is shown. Statistical significance was assessed by Spearman correlation. EFR, effluent flow rate
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