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.
Highlights
Sepsis is an important cause of acute kidney injury (AKI) in critically ill patients, and half of these patients require acute renal support (ARS) [1,2,3,4]; the adoption of measures that aim to reduce mortality, as well as the costs associated with treatment and hospitalization, remain a huge challenge.Among these measures, early administration of antimicrobial in the appropriate dose is highly impactful [5,6,7]
The objective of this study was to evaluate the reduction in vancomycin by different methods of dialysis (IHD and prolonged haemodialysis (PHD)) in critical patients with AKI associated with sepsis, through a pharmacokinetic approach and pharmacokinetic-pharmacodynamic modelling, in order to identify the factors related to subtherapeutic concentrations
From March 2015 to August 2017, 27 patients treated with intermittent haemodialysis (IHD), 17 patients treated with PHD for 6 h and 11 patients treated for PHD for 10 h were included
Summary
Sepsis is an important cause of acute kidney injury (AKI) in critically ill patients (over 50% of cases), and half of these patients require acute renal support (ARS) [1,2,3,4]; the adoption of measures that aim to reduce mortality, as well as the costs associated with treatment and hospitalization, remain a huge challenge Among these measures, early administration of antimicrobial in the appropriate dose is highly impactful [5,6,7]. The pharmacodynamics of antibiotic drugs in critically ill patients are greatly modified and poorly known due to alterations in their absorption, distribution, metabolism and elimination [8,9,10] Another as yet unclarified question is the correct adjustment of the antimicrobial dosage in AKI patients and in dialytic therapy [4,11], aiming to avoid toxicity and subtherapeutic concentrations, which may contribute to higher mortality [12].
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