Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program

Background: Area under the curve to minimum inhibitory concentration (AUC/MIC) has been recommended by the 2020 updated vancomycin guidelines for dosing vancomycin for both efficacy and safety. Previously, AUC/MIC has been cumbersome to calculate so surrogate trough concentrations of 15-20 mg/dL were utilized. However, trough-based dosing is not a sufficient surrogate as AUC/MIC targets of 400-600 can usually be reached without achieving troughs of 15-20 mg/dL. Targeting higher trough levels may also lead to adverse events including acute kidney injury (AKI) and nephrotoxicity. Objective: To compare the mean total first day vancomycin dose in traditional trough-based dosing versus dosing recommended by an AUC/MIC dosing program. Methods: Adult inpatients who received at least 24 hours of IV vancomycin treatment were included in this single-center, retrospective cohort study. The primary endpoint was difference in mean total first day vancomycin dose in milligrams (mg) received between patients’ traditional trough-based dosing and recommended dose via AUC/MIC electronic dosing calculator. Patients served as their own control by analyzing both actual dose received and dose recommended by the electronic AUC/MIC program. Rates of vancomycin induced adverse events, including acute kidney injury, elevated steady-state trough concentrations, and Red Man’s syndrome were also compared between patients who received doses consistent with the AUC/MIC dosing recommendation versus those who did not. Results: 264 patients were included in this study. Initial 24-hour vancomycin exposure was significantly lower with the recommended AUC/MIC dose versus the dose received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI 114.7:423.1] p=0.0007). Conclusions: Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in lower total first day vancomycin doses.

Download Full-text

Evaluation of vancomycin initial trough levels in children: A 1-year retrospective study

SAGE Open Medicine ◽

10.1177/2050312120951058 ◽

2020 ◽

Vol 8 ◽

pp. 205031212095105

Author(s):

Muhammad Salem ◽

Ahmed Khalil ◽

Asmaa Mohamed ◽

Ahmed Elmasoudi

Keyword(s):

Acute Kidney Injury ◽

Congenital Heart Disease ◽

Retrospective Study ◽

Congenital Heart ◽

Kidney Injury ◽

Baseline Serum ◽

Fourth Dose ◽

The Mean ◽

Trough Levels ◽

Effect Of Age

Background and objectives: Achieving vancomycin therapeutic levels is essential for antibacterial success and resistance prevention. Multiple studies have shown that most of the children fail to reach therapeutic trough levels (10–20 µg/mL). This study aims to determine the frequency of achieving therapeutic vancomycin initial trough levels in children, evaluate the effect of age on that achievement and the mean initial trough levels, and the frequency of supratherapeutic levels. Methods: Children aged 1 month to 12 years who received three or more vancomycin doses 15 mg/kg every 6 h while admitted at our hospital from February 2016 to January 2017, and had a level before the fourth dose were included. Cases with high baseline serum creatinine, acute kidney injury, and congenital heart disease were excluded. Results: Out of 75 included cases, one third, 28/75 (37.3%), achieved goal. The lowest frequency was 6/28 (21.4%) of the 2–5 years group, which were statistically less likely to achieve, and had significantly lower mean initial trough than the 1–23 months group ( P = 0.026 and 0.013, respectively). Mean initial trough levels were 10.1, 7.3, and 8.2 µg/mL in the 1–23 months, 2–5 years, and 6–12 years groups, respectively ( P = 0.014). No supratherapeutic levels were observed. Conclusion: Vancomycin dose of 60 mg/kg/day is insufficient to attain target levels for most of the children. Children aged 2–5 years are the least likely to achieve and have the lowest mean levels. More intensified doses are warranted to be studied prospectively to identify the most effective empiric dose for children.

Download Full-text

Vancomycin Dosing and Pharmacokinetics in Postoperative Pediatric Cardiothoracic Surgery Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-21.1.66 ◽

2016 ◽

Vol 21 (1) ◽

pp. 66-74 ◽

Cited By ~ 4

Author(s):

Emily C. Benefield ◽

Tracy M. Hagemann ◽

H. Christine Allen ◽

Kevin Farmer ◽

Michael E. Burton ◽

...

Keyword(s):

Acute Kidney Injury ◽

Area Under The Curve ◽

Kidney Injury ◽

Primary Objective ◽

Cardiothoracic Surgery ◽

Pharmacokinetic Parameters ◽

Control Group ◽

Future Prospective Study ◽

Trough Concentrations ◽

High Degree

OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of ≥400. RESULTS: Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p < 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p<0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC ≥400. CONCLUSIONS: Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI.

Download Full-text

1570. Association Between Vancomycin Area Under the Curve (AUC) and Nephrotoxicity

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1434 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S574-S574

Author(s):

Anna Poston-Blahnik ◽

Ryan P Moenster

Keyword(s):

Acute Kidney Injury ◽

Length Of Stay ◽

Area Under The Curve ◽

Kidney Injury ◽

Multivariate Logistic Regression Model ◽

Bivariate Analysis ◽

P Value ◽

Antibiotic Administration ◽

Secondary Outcomes ◽

Vancomycin Treatment

Abstract Background It is unclear whether increased vancomycin area under the curve (AUC) contributes to acute kidney injury (AKI) risk. Methods This retrospective cohort study was undertaken to determine whether vancomycin AUC > 550 is associated with a higher rate of AKI than an AUC < 550. Patients treated with vancomycin for at least 4 days at the St. Louis VA from 1/1/2016–9/31/2018 were included. The primary outcome was AKI (defined as an increase in serum creatinine by 0.3 mg/dL or 50% from baseline). Secondary outcomes included length of stay, readmission, or mortality in 30 days, AKI rate with concurrent antibiotics, and AKI rate with comorbidities. The AUC was calculated as daily dose (in mg) divided by vancomycin clearance. The variables of age ≥ 70, vancomycin AUC ≥ 550, creatinine clearance (CrCl) < 50 mL/minute, concomitant antibiotic administration, vancomycin treatment ≤ 7 days, and the presence of comorbidities were included in a bivariate analysis. Variables with a P-value of <0.2 were included in a multivariate logistic regression model. Results Two hundred patients were included in the analysis; 100 patients with an AUC ≥ 550, and 100 with an AUC < 500. Only mean vancomycin dose (1722.50 mg vs. 2361.25 mg; P < 0.05), mean AUC (465.88 vs. 696.45; P < 0.05), and peak SCr (1.22 mg/dL vs. 1.48 mg/dL; P = 0.015) were significantly different between groups; AUC < 550 vs. AUC ≥ 550, respectively. Acute kidney injury occurred in 22% (44/200) of all patients; 42% (42/100) with a calculated AUC ≥ 550 developed AKI compared with 2% (2/100) of patients with an AUC < 550 (P < 0.05). The secondary outcomes of concomitant nephrotoxic agents, length of stay, readmission at 30 days, and 30-day mortality were not significantly different between groups. Only age ≥ 70, vancomycin AUC ≥ 550, CrCl < 50 mL/minute, concomitant piperacillin–tazobactam administration, and the presence of comorbidities were included in the multivariate regression. Age ≥ 70, CrCl < 50 mL/minute, and AUC ≥ 550 [OR 49.5 (95% CI 10.1 – 242.3; P < 0.05)] were found to be independently associated with risk for developing AKI. Conclusion Patients with a calculated vancomycin AUC ≥ 550 were found to have a significantly higher rate of AKI compared with those with an AUC < 550. Disclosures All authors: No reported disclosures.

Download Full-text

The Serum Concentration of Vancomycin as a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Critically Ill Patients

Antibiotics ◽

10.3390/antibiotics11010112 ◽

2022 ◽

Vol 11 (1) ◽

pp. 112

Author(s):

Welder Zamoner ◽

Karina Zanchetta Cardoso Eid ◽

Lais Maria Bellaver de Almeida ◽

Isabella Gonçalves Pierri ◽

Adriano dos Santos ◽

...

Keyword(s):

Serum Concentration ◽

Critically Ill ◽

Critically Ill Patients ◽

Area Under The Curve ◽

Kidney Injury ◽

Controversial Topic ◽

Trough Concentrations ◽

Cox Analysis ◽

The Impact ◽

Trough Levels

The impact of serum concentrations of vancomycin is a controversial topic. Results: 182 critically ill patients were evaluated using vancomycin and 63 patients were included in the study. AKI occurred in 44.4% of patients on the sixth day of vancomycin use. Vancomycin higher than 17.53 mg/L between the second and the fourth days of use was a predictor of AKI, preceding AKI diagnosis for at least two days, with an area under the curve of 0.806 (IC 95% 0.624–0.987, p = 0.011). Altogether, 46.03% of patients died, and in the Cox analysis, the associated factors were age, estimated GFR, CPR, and vancomycin between the second and the fourth days. Discussion: The current 2020 guidelines recommend using Bayesian-derived AUC monitoring rather than trough concentrations. However, due to the higher number of laboratory analyses and the need for an application to calculate the AUC, many centers still use therapeutic trough levels between 15 and 20 mg/L. Conclusion: The results of this study suggest that a narrower range of serum concentration of vancomycin was a predictor of AKI in critically ill septic patients, preceding the diagnosis of AKI by at least 48 h, and it can be a useful monitoring tool when AUC cannot be used.

Download Full-text

Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial

International Journal of Nephrology ◽

10.1155/2021/8833278 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Jonathan S. Chávez-Iñiguez ◽

Jorge L. Poo ◽

Miguel Ibarra-Estrada ◽

Leonel García-Benavides ◽

Guillermo Navarro-Blackaller ◽

...

Keyword(s):

Clinical Trial ◽

Acute Kidney Injury ◽

Adverse Events ◽

Kidney Injury ◽

Primary Objective ◽

Controlled Clinical Trial ◽

Prolonged Release ◽

Double Blind ◽

Septic Acute Kidney Injury ◽

The Mean

Background. There is no treatment for septic acute kidney injury (sAKI). The anti-inflammatory activity of prolonged-release pirfenidone (PR-PFD) could be beneficial in this clinical setting. Methods. This study was a double-blind randomized clinical trial in sAKI patients with nephrology consultation at the Civil Hospital of Guadalajara, in addition to the usual treatment of AKI associated with sepsis; patients were randomized to receive either PR-PFD at 1,200 mg/day (group A) or 600 mg/day (group B) or a matched placebo for 7 consecutive days. The primary objective was the decrease in serum creatinine (sCr) and increase in urinary volume (UV); the secondary objectives were changes in serum electrolytes, acid-base status, and mortality. Results. Between August 2016 and August 2017, 88 patients were randomized. The mean age was 54 (17 ± SD) years, and 47% were male. The main site of infection was the lung (39.8%), septic shock was present in 39.1% of the cases, and the mean SOFA score was 8.8 points. 28 patients received PFD 1,200 mg, 30 patients received PFD 600 mg, and 30 patients received placebo. During the study, sCr did not differ among the groups. The reversion rate of sCr, UV, and mortality was not different among the groups ( p = 0.70 , p = 0.47 , and p = 0.38 , respectively). Mild adverse events were not different among the groups. Conclusion. PR-PFD did not improve the clinical course of sAKI and seemed to be safe in terms of adverse events. This trial is registered with NCT02530359.

Download Full-text

Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-26.7.746 ◽

2021 ◽

Vol 26 (7) ◽

pp. 746-752

Author(s):

Tyler E. Bosley ◽

Robert J. Kuhn ◽

Brian Gardner ◽

Elizabeth B. Autry ◽

Madeline Fuller ◽

...

Keyword(s):

Acute Kidney Injury ◽

Area Under Curve ◽

Pediatric Patients ◽

Inhibitory Concentration ◽

Area Under The Curve ◽

Kidney Injury ◽

Target Area ◽

Single Center ◽

Age Cohorts ◽

The Mean

OBJECTIVE Vancomycin dosing requirements to achieve a target area under curve/minimum inhibitory concentration (AUC/MIC) of 400 to 600 mg•hr/L have not been established in pediatrics. Dose modeling studies and recent guidelines suggest dosing higher than historical recommendations. This study examines dosing requirements to achieve target AUC/MIC in human pediatric patients. METHODS This retrospective study includes 77 patients, aged 1 month to 18 years, at a single center, who received at least 2 days of intravenous vancomycin with a pharmacokinetic monitoring note and calculated AUC/MIC. Dosing to achieve target AUC/MIC was evaluated by age and indication. Nephrotoxicity was also assessed. RESULTS The mean dose required to achieve target AUC/MIC for all patients was 67.7 mg/kg/day. Adjusting for age, the mean dose required to achieve target AUC/MIC of 400 to 600 mg•hr/L was found to be statistically significantly different among 3 age cohorts: 1 month to 5 years, 6 to 12 years, and 13 to 18 years [F(2,74) = 15.32, p < 0.001], with mean requirements of 79 ± 14.1, 65.6 ± 21.1, and 53.9 ± 17.1 mg/kg/day, respectively. Dosing requirements were also found to be statistically significantly different across indications [F(6,70) = 4.84, p < 0.001]. Acute kidney injury was identified in 5 patients (6.5%). CONCLUSIONS The vancomycin dose required to achieve target AUC/MIC in pediatrics was significantly higher in younger pediatric patients and ranged from 53.9 to 79 mg/kg/day, confirming recent guideline recommendations. Doses can be further adjusted for indication. Nephrotoxicity rates remain low compared with historical rates with single trough monitoring.

Download Full-text

P0614URINARY EXOSOMAL MICRORNA-21 AS A MARKER OF SCRUB TYPHUS-ASSOCIATED ACUTE KIDNEY INJURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0614 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

In O Sun ◽

Kwang Young Lee ◽

A Young Cho

Keyword(s):

Acute Kidney Injury ◽

Kidney Disease ◽

Scrub Typhus ◽

Area Under The Curve ◽

Kidney Injury ◽

Diagnostic Value ◽

Cross Sectional Study ◽

Total Leukocyte Count ◽

Cross Sectional ◽

Exosomal Mirna

Abstract Background and Aims Urinary microRNA (miRNA)-21 is reported to be a biomarker for detection of acute kidney injury (AKI). Analysis of urinary exsome may serve as a novel diagnostic approach in kidney disease. The aim of this study is to investigate the clinical significance of urinary exosomal miRNA-21 for AKI in patients with scrub typhus. Method In a cross-sectional study, we collected 138 urine samples at the time of admission from 145 patients with scrub typhus. For 25 patients with scrub typhus-associated AKI and 25 age, sex-matched scrub typhus patient without AKI, we measured miRNA-21 in urinary exosomal fraction and compared diagnostic value in predictiong AKI. Results Compared with patients in the non-AKI group, patients in the AKI group were more likely to have one or more comorbidity such as diabetes (50% vs. 5%, P<0.01) and chronic kidney disease (8% vs. 0%, P<0.01). Total leukocyte count were higher in patients with AKI than in those without AKI (10.40 × 103/ mL vs. 6.40 × 103/mL, P<0.01). The levels of urinary miRNA-21 were higher in the AKI group than in the non-AKI group. Urinary exosomal miRNA-21 levels correlated directly with serum neutrophil gelatinase-associated lipocalin values and total leukocyte counts and inversely with estimated glomerular filtration rate. The receiver operator characteristics curve analysis for urinary exosomal miRNA-21 showed good discriminative power for the diagnosis of scrub typhus-associated AKI, with area under the curve value of 0.907. Conclusion Urinary exosomal miRNA-21 could be a surrogate markers for the diagnosis of scrub typhus–associated AKI.

Download Full-text

Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

Paediatrica Indonesiana ◽

10.14238/pi56.4.2016.230-7 ◽

2016 ◽

Vol 56 (4) ◽

pp. 230

Author(s):

Meta Herdiana Hanindita ◽

Riskky Vitria Prasetyo ◽

Ninik Asmaningsih Soemyarso ◽

I Ketut Alit Utamayasa ◽

Paul Tahalele

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Creatinine Clearance ◽

Sensitivity And Specificity ◽

Area Under The Curve ◽

Kidney Injury ◽

Schwartz Formula ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Plasma Ngal ◽

Neutrophil Gelatinase

Background Acute kidney injury (AKI) is still diagnosed by measuring the estimated creatinine clearance (eCCl), despite the fact that it may not change until 50% or more of kidney function has been lost. AKI after cardiac surgery is related to prolonged intensive care, decreased quality of life, and increased long term mortality. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early biomarker of AKI, which may be useful for assessing AKI in cardiac patients.Objective To determine the validity of urinary and plasma NGAL as biomarkers for AKI in children after cardiac surgery.Methods Subjects were children who underwent cardiac surgery in Dr. Soetomo Hospital, Surabaya, Indonesia from August 2013 to January 2014. Serial urine and blood samples were analyzed for NGAL before surgery, as well as at 2h, 4h, 12h, and 24h after surgery. The AKI was established based on pRIFLE criteria. Estimated creatinine clearance (eCCl) was calculated from the estimated glomerular filtration rate (eGFR), according to age by the traditional Schwartz formula. Serum creatinine was assayed by the Jaffe method before surgery, as well as at 12h, 24h, 48h, and 72h after surgery.Results Of 20 subjects, 5 developed AKI. Urinary and plasma NGAL increased markedly at 2h postoperatively, as compared to eGFR which showed a rise at 12-48 h after cardiac surgery. Analysis of 2h post-operative urinary NGAL at a cut off value of 11.270ng/mL yielded an area under the curve (AUC) of 1.00 (95%CI 2.63 to 12.13), with sensitivity and specificity of 100% each for AKI. In addition, 2h post-operative plasma NGAL at a cut off value of 8.385 ng/mL yielded an AUC of 1.00 (95%CI 3.71 to 12.15) with sensitivity and specificity of 100% each for AKI.Conclusion Urinary and plasma NGAL are valid as early biomarkers for AKI in children after cardiac surgery.

Download Full-text

Snake envenomation-induced acute kidney injury: prognosis and long-term renal outcomes

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2020-139021 ◽

2021 ◽

pp. postgradmedj-2020-139021

Author(s):

Manoj Kumar ◽

Maasila Arcot Thanjan ◽

Natarajan Gopalakrishnan ◽

Dhanapriya Jeyachandran ◽

Dineshkumar Thanigachalam ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Long Term Outcomes ◽

Urine Protein ◽

Renal Outcomes ◽

Snake Envenomation ◽

The Mean ◽

New Onset

BackgroundSnake bite continues to be a significant cause of acute kidney injury (AKI) in India. There is paucity of data regarding long-term outcomes of such patients. In this study, we aim to assess the prognosis and long-term renal outcomes of such patients.MethodsWe analysed the hospital records of snake envenomation-induced AKI from January 2015 to December 2018. Predictors of in-hospital mortality were assessed. Survivors were advised to visit follow-up clinic to assess their kidney function.ResultsThere were 769 patients with evidence of envenomation and of them, 159 (20.7%) had AKI. There were 112 (70.4%) males. Mortality occurred in 9.4% of patients. Logistic regression analysis identified shock (OR 51.949, 95% CI 4.297 to 628.072) and thrombocytopenia (OR 27.248, 95% CI 3.276 to 226.609) as predictors of mortality. Forty-three patients attended the follow-up. The mean follow-up duration was 30.4±15.23 months. Adverse renal outcomes (eGFR <60 mL/min/1.73 m2 or new-onset hypertension (HTN) or pre-HTN or urine protein creatinine ratio >0.3) occurred in 48.8% of patients. Older age (mean age (years) 53.3 vs 42.8, p=0.004) and longer duration on dialysis (median duration (days) 11.5 vs 5, p=0.024) were significantly associated with adverse renal outcomes.ConclusionsThe incidence of AKI in snake envenomation was 20.7%. The presence of shock and thrombocytopenia were associated with mortality. Adverse renal outcomes occurred in 48.8% of patients in the long term.

Download Full-text

Neutrophil gelatinase associated lipocalin, an early biomarker for diagnosis of acute kidney injury after percutaneous coronary intervention

Turkish Journal of Biochemistry ◽

10.1515/tjb-2017-0004 ◽

2017 ◽

Vol 43 (1) ◽

pp. 15-21 ◽

Cited By ~ 1

Author(s):

Nakhshab Choudhry ◽

Amna Ihsan ◽

Sadia Mahmood ◽

Fahim Ul Haq ◽

Aamir Jamal Gondal

Keyword(s):

Acute Kidney Injury ◽

Percutaneous Coronary Intervention ◽

Serum Creatinine ◽

Kidney Injury ◽

Coronary Intervention ◽

Diagnostic Biomarker ◽

Elective Percutaneous Coronary Intervention ◽

Percutaneous Coronary ◽

Significant Difference ◽

The Mean

AbstractObjectives:This study was designed to find the reliability of serum NGAL as an early and better diagnostic biomarker than that of serum creatinine for acute kidney injury after percutaneous coronary intervention in Pakistani population.Materials and methods:One hundred and fifty-one patients undergoing elective percutaneous coronary intervention were included and demographic data were recorded. Blood was drawn by venipuncture in clot activator vacutainers and serum was separated and stored at 4°C. Sample was drawn before the percutaneous procedure and subsequently sampling was done serially for 5 days.Results:The mean±SD serum NGAL pre-PCI (39.92± 10.35 μg/L) and 4 h post-PCI (100.42±26.07 μg/L) showed highly significant difference (p<0.001). The mean±SD serum creatinine pre-PCI (70.1±11.8 μmol/L) and post-PCI (71.2±11.6 μmol/L) showed significant difference (p=0.005) on day 2 onwards but mean microalbumin showed insignificant results (p=0.533). The serum NGAL predicted CI-AKI with sensitivity of 95.8% and specificity of 97.6% for a cut off value of 118 μg/L.Conclusion:Our results suggest that NGAL is an excellent early diagnostic biomarker for acute kidney injury in patients undergoing elective percutaneous coronary intervention.

Download Full-text