Vancomycin for Dialytic Therapy in Critically Ill Patients: Analysis of Its Reduction and the Factors Associated with Subtherapeutic Concentrations

Abstract

This study aimed to evaluate the reduction in vancomycin through intermittent haemodialysis (IHD) and prolonged haemodialysis (PHD) in acute kidney injury (AKI) patients with sepsis and to identify the variables associated with subtherapeutic concentrations. A prospective study was performed in patients admitted at an intensive care unit (ICU) of a Brazilian hospital. Blood samples were collected at the start of dialytic therapy, after 2 and 4 h of treatment and at the end of therapy to determine the serum concentration of vancomycin and thus perform pharmacokinetic evaluation and PK/PD modelling. Twenty-seven patients treated with IHD, 17 treated with PHD for 6 h and 11 treated with PHD for 10 h were included. The reduction in serum concentrations of vancomycin after 2 h of therapy was 26.65 ± 12.64% and at the end of dialysis was 45.78 ± 12.79%, higher in the 10-h PHD group, 57.70% (40, 48–64, 30%) (p = 0.037). The ratio of the area under the curve to minimal inhibitory concentration (AUC/MIC) at 24 h in the PHD group was significantly smaller than at 10 h (p = 0.047). In the logistic regression, PHD was a risk factor for an AUC/MIC ratio less than 400 (OR = 11.59, p = 0.033), while a higher serum concentration of vancomycin at T0 was a protective factor (OR = 0.791, p = 0.009). In conclusion, subtherapeutic concentrations of vancomycin in acute kidney injury (AKI) patients in dialysis were elevated and may be related to a higher risk of bacterial resistance and mortality, besides pointing out the necessity of additional doses of vancomycin during dialytic therapy, mainly in PHD.

Antimicrobial dosing in prolonged intermittent renal replacement therapy: a systematic review

“…Dosing should be given at least 30-mins before a PIRRT treatment to allow a high Cmax to be achieved. 22 Vancomycin dosing and PK in PIRRT has been comparatively well investigated, including small prospective PK studies of critically ill patients with AKI 16,17,[23][24][25][26][27] ; three combined with a MCS population PK simulation. [28][29][30] Vancomycin clearance on-PIRRT is higher, although varies significantly (33-150%) 16,25,28,29 and depends on dialysis settings, including the filter membrane and PIRRT duration.…”

“…26 Doses should be given after PIRRT and supplemented by TDM to guide ongoing dosing. 16,17,27 PK variability is significant and dosing without TDM risks significant proportions of patients manifesting potentially toxic exposures (AUC24 > 700 mg h/L). 30 PIRRT causes increased clearance of colistin compared to non-PIRRT periods.…”

“…Vancomycin dosing and PK in PIRRT has been comparatively well investigated, including small prospective PK studies of critically ill patients with AKI 16,17,23–27 ; three combined with a MCS population PK simulation 28–30 …”

“…Maintenance vancomycin dose recommendations vary, likely due to the effect of different PIRRT settings, and may be fixed (between 500 mg–1600 mg once daily) or weight‐based (15–20 mg/kg daily) 26 . Doses should be given after PIRRT and supplemented by TDM to guide ongoing dosing 16,17,27 . PK variability is significant and dosing without TDM risks significant proportions of patients manifesting potentially toxic exposures (AUC24 > 700 mg h/L) 30 …”

Risk Scoring System for Vancomycin-Associated Acute Kidney Injury

“…Moreover, we included patients with CKD and found that their renal impairment status was not significantly related to the risk of AKI. The broad spectrum of diseases in our studied population, which included patients with CKD, is notable in that previous studies have mainly dealt with patients with CKD patients alone or excluded these renally impaired populations ( Liu et al, 2018 ; Freitas et al, 2020 ; Gaggl et al, 2020 ; Imai et al, 2020 ). Thus, our scoring system for AKI can be generalized to patients with various types and severities of diseases.…”