Abstract
Introduction
Augmented renal clearance (ARC) increases vancomycin (VCM) clearance. Therefore, higher
VCM doses are recommended in patients with ARC; however, impacts of ARC on the area
under the concentration–time curve (AUC) discrepancies between initial dosing design
and therapeutic drug monitoring (TDM) period remains unclear.
Methods
We retrospectively collected data from critically ill patients treated with VCM. The
primary endpoint was the association between ARC and AUC24–48h deviations. ARC and AUC deviation were defined as a serum creatinine clearance (CCr)
≥130 mL/min/1.73 m2 and an AUC at TDM 30% or more higher than the AUC at the initial dosing design, respectively.
The pharmacokinetic profiles of VCM were analyzed with the trough levels or peak/trough
levels using the Bayesian estimation software Practical AUC-guided TDM (PAT).
Results
Among 141 patients (median [IQR]; 66 [58–74] years old; 30% women), 35 (25%) had ARC.
AUC deviations were significantly more frequent in the ARC group than in the non-ARC
group (20/35 [57.1%] and 17/106 [16.0%] patients, respectively, p < 0.001). Age- and
sex-adjusted multivariate analyses revealed that the number of VCM doses before TDM
≥5 (odds ratio, 2.56; 95% confidence interval [CI]: 1.01–6.44, p = 0.047) and CCr
≥130 mL/min/1.73 m2 were significantly associated with AUC deviations (odds ratio, 7.86; 95%CI: 2.91–21.19,
p < 0.001).
Conclusion
Our study clarifies that the AUC of VCM in patients with ARC is higher at the time
of TDM than at the time of dosage design.
Keywords
Abbreviations:
ARC (augmented renal clearance), BMI (body mass index), MIC (minimum inhibitory concentration), MRSA (methicillin-resistant Staphylococcus aureus), NPV (negative predictive value), PPV (positive predictive value), PS (propensity score), ROC (receiver operating characteristic), SD (standard deviation), SOFA (sequential organ failure assessment), TDM (therapeutic drug monitoring)To read this article in full you will need to make a payment
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References
- Epidemiology, appropriateness, and cost of vancomycin use.Clin Infect Dis. 1998; 26: 1200-1203https://doi.org/10.1086/520284
- The epidemiology of intravenous vancomycin usage in a university hospital. A 10-year study.JAMA. 1993; 269 (PMID: 8240468): 598-602
- Clinical pharmacokinetics of vancomycin.Clin Pharmacokinet. 1986; 11 (PMID: 3530582): 257-282https://doi.org/10.2165/00003088-198611040-00001
- Prevalence and risk factors of augmented renal clearance: a systematic review and meta-analysis.Pharmaceutics. 2022; 14 (PMID: 35214177; PMCID: PMC8878755): 445https://doi.org/10.3390/pharmaceutics14020445
- Impact of area under the concentration-time curve to minimum inhibitory concentration ratio on vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus bacteraemia.Int J Antimicrob Agents. 2015; 46: 689-695https://doi.org/10.1016/j.ijantimicag.2015.09.010
- Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?.Diagn Microbiol Infect Dis. 2021; 101115442https://doi.org/10.1016/j.diagmicrobio.2021.115442
- Augmented renal clearance in critical illness: an important consideration in drug dosing.Pharmaceutics. 2017; 9: 36https://doi.org/10.3390/pharmaceutics9030036
- Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial.Int J Antimicrob Agents. 2017; 49: 624-630https://doi.org/10.1016/j.ijantimicag.2016.12.022
- Identification of vancomycin exposure-toxicity thresholds in hospitalized patients receiving intravenous vancomycin.Antimicrob Agents Chemother. 2017; 62 (e01684-17, PMID: 29084753; PMCID: PMC5740375)https://doi.org/10.1128/AAC.01684-17
- Comparison of trough concentration and area under the curve of vancomycin associated with the incidence of nephrotoxicity and predictors of a high trough level.J Infect Chemother. 2021; 27: 455-460https://doi.org/10.1016/j.jiac.2020.10.014
- Accuracy of short-duration creatinine clearance determinations in predicting 24-hour creatinine clearance in critically ill and injured patients.J Trauma. 2002; 53: 267-271https://doi.org/10.1097/00005373-200208000-00013
- Accuracy of 2- and 8-hour urine collections for measuring creatinine clearance in the hospitalized elderly.Pharmacotherapy. 1993; 13 (PMID: 8469620): 135-142
- Population pharmacokinetic modeling and dose optimization of vancomycin in Chinese patients with augmented renal clearance.Antibiotics (Basel). 2021; 10 (PMID: 34680818; PMCID: PMC8532702): 1238https://doi.org/10.3390/antibiotics10101238
- Population pharmacokinetics of vancomycin in Chinese patients with augmented renal clearance.J Infect Public Health. 2020; 13 (PMID: 31277936): 68-74https://doi.org/10.1016/j.jiph.2019.06.016
- Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations.Crit Care Med. 2014; 42: 520-527https://doi.org/10.1097/CCM.0000000000000029
- Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy.J Crit Care. 2013; 28: 695-700https://doi.org/10.1016/j.jcrc.2013.03.003
- The emperor's new clothes: prospective observational evaluation of the association between initial vancomycIn exposure and failure rates among adult hospitalized patients with methicillin-resistant Staphylococcus aureus bloodstream infections (PROVIDE).Clin Infect Dis. 2020; 70: 1536-1545https://doi.org/10.1093/cid/ciz460
- Performance of area under the concentration-time curve estimations of vancomycin with limited sampling by a newly developed web application.Pharm Res (N Y). 2021; 38: 637-646https://doi.org/10.1007/s11095-021-03030-y
- Prediction of creatinine clearance from serum creatinine.Nephron. 1976; 16 (PMID: 1244564): 31-41https://doi.org/10.1159/000180580
- Revised equations for estimated GFR from serum creatinine in Japan.Am J Kidney Dis. 2009; 53: 982-992https://doi.org/10.1053/j.ajkd.2008.12.034
- Collaborators Developing the Japanese Equation for Estimated GFR. GFR estimation using standardized serum cystatin C in Japan.Am J Kidney Dis. 2013; 61: 197-203https://doi.org/10.1053/j.ajkd.2012.07.007
- Vancomycin exposure in patients with methicillin-resistant Staphylococcus aureus bloodstream infections: how much is enough?.Clin Infect Dis. 2014; 59: 666-675https://doi.org/10.1093/cid/ciu398
- Comparison of trough concentration and area under the curve of vancomycin associated with the incidence of nephrotoxicity and predictors of a high trough level.J Infect Chemother. 2021; 27: 455-460https://doi.org/10.1016/j.jiac.2020.10.014
- Population pharmacokinetics of vancomycin in Japanese adult patients.Ther Drug Monit. 1998; 20 (PMID: 9558127): 139-148https://doi.org/10.1097/00007691-199804000-00003
- Estimated GFR: time for a critical appraisal.Nat Rev Nephrol. 2019; 15: 177-190https://doi.org/10.1038/s41581-018-0080-9
- Overestimation of glomerular filtration rate by creatinine-based equation in heart failure patients is predicted by a novel scoring system.Geriatr Gerontol Int. 2020; 20: 752-758https://doi.org/10.1111/ggi.13959
- Utility of the sarcopenia index for assessment of muscle mass and nutritional status in patients with chronic heart failure: comparison with anthropometric parameters.Geriatr Gerontol Int. 2020; 20: 388-389https://doi.org/10.1111/ggi.13876
- Predictors of augmented renal clearance in a heterogeneous ICU population as defined by creatinine and cystatin C.Nephron. 2020; 144: 313-320https://doi.org/10.1159/000507255
- Estimation of creatinine clearance using plasma creatinine or cystatin C: a secondary analysis of two pharmacokinetic studies in surgical ICU patients.BMC Anesthesiol. 2015; 15: 62https://doi.org/10.1186/s12871-015-0043-7
- How to estimate kidney function in kidney transplant recipients with mild to moderate kidney impairment: comparison of estimated glomerular filtration (eGFR) values between creatinine-based GFR equations and cystatin C-based GFR equations for Japanese population.Clin Exp Nephrol. 2014; 18: 130-134https://doi.org/10.1007/s10157-013-0811-y
- Cystatin C-guided vancomycin dosing in critically ill patients: a quality improvement project.Am J Kidney Dis. 2017; 69: 658-666https://doi.org/10.1053/j.ajkd.2016.11.016
- A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia.Clin Therapeut. 2007; 29: 1107-1115https://doi.org/10.1016/j.clinthera.2007.06.014
- Reduced hydration status characterized by disproportionate elevation of blood urea nitrogen to serum creatinine among the patients with cerebral infarction.Med Hypotheses. 2011; 77: 601-604https://doi.org/10.1016/j.mehy.2011.06.044
- A high urea-to-creatinine ratio predicts long-term mortality independent of acute kidney injury among patients hospitalized with an infection.Sci Rep. 2020; 1015649https://doi.org/10.1038/s41598-020-72815-9
- Massive and disproportionate elevation of blood urea nitrogen in acute azotemia.Int Urol Nephrol. 2002; 34: 143-145https://doi.org/10.1023/a:1021346401701
- Linezolid: pharmacokinetic characteristics and clinical studies.Clin Microbiol Infect. 2001; 7: 75-82https://doi.org/10.1046/j.1469-0691.2001.00061.x
- Impact of augmented renal clearance on the pharmacokinetics of linezolid: advantages of continuous infusion from a pharmacokinetic/pharmacodynamic perspective.Int J Infect Dis. 2020; 93: 329-338https://doi.org/10.1016/j.ijid.2020.02.044
- Plasma trough concentration distribution and safety of high-dose teicoplanin for patients with augmented renal clearance [published online ahead of print, 2022 May 28].J Clin Pharm Therapeut. 2022; (10.1111/jcpt.13700)https://doi.org/10.1111/jcpt.13700
- Population pharmacokinetics of daptomycin.Antimicrob Agents Chemother. 2004; 48: 2799-2807https://doi.org/10.1128/AAC.48.8.2799-2807.2004
Article info
Publication history
Published online: May 08, 2023
Accepted:
April 28,
2023
Received in revised form:
April 12,
2023
Received:
February 17,
2023
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
