The Relationship of Nephrotoxicity to Vancomycin Trough Serum Concentrations in a Veteran's Population: A Retrospective Analysis

2012 ◽  
Vol 46 (11) ◽  
pp. 1477-1483 ◽  
Author(s):  
Amy Horey ◽  
Kari A Mergenhagen ◽  
Arun Mattappallil
Keyword(s):  
Trough Concentration ◽  
Multiple Logistic Regression Analysis ◽  
Therapeutic Monitoring ◽  
Vancomycin Therapy ◽  
Baseline Serum ◽  
Trough Serum ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
Stage Renal Disease ◽  
End Stage

BACKGROUND: The risk of vancomycin-associated nephrotoxicity varies greatly depending on the trough concentration. Recent guidelines suggest target vancomycin trough concentrations of 15–20 mg/L as a predictor of efficacy in the treatment of severe gram-positive infections. Limited data exist quantifying the risk for nephrotoxicity with various ranges of vancomycin troughs. OBJECTIVE: To determine the occurrence of nephrotoxicity during vancomycin therapy and up to 72 hours after its completion, in relation to the maximum trough concentration value, and identify risk factors that impact nephrotoxicity associated with vancomycin use. METHODS: We reviewed the medical records of veterans with a baseline serum creatinine less than 2 mg/dL who received 48 or more hours of vancomycin therapy and had 1 or more vancomycin trough samples obtained within 96 hours of therapy initiation from January 1, 2006, to November 1, 2008, to determine the occurrence of nephrotoxicity (as defined by RIFLE [Risk, Injury, Failure, Loss, and End-stage renal disease] criteria). RESULTS: Thirty-four (12.6%) patients developed nephrotoxicity. In multiple logistic regression analysis, maximum trough concentrations (OR 1.14; 95% CI 1.09 to 1.20), documented hypotension (OR 4.7; 95% CI 1.3 to 16.4), and weight (OR 1.02; 95% CI 1.0 to 1.03) were found to be significantly associated with the occurrence of nephrotoxicity. Once stratified into ranges of 5–10 mg/L (4.9%), 10.1–15 mg/L (3.1%), 15.1–20 mg/L (10.6%), 20.1–35 mg/L (23.6%), and greater than 35 mg/L (81.8%), increasing trough ranges were associated with a subsequently higher risk of nephrotoxicity. CONCLUSIONS: In the population evaluated, hypotension and trough concentrations were predictors of nephrotoxicity; elevated vancomycin trough concentration had the highest odds of association. These data reinforce the close therapeutic monitoring guidelines for vancomycin trough concentrations, especially when targeting troughs of 15–20 mg/L.

scholarly journals Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates

2018 ◽  
Vol 62 (4) ◽  
pp. e01647-17 ◽  
Author(s):  
Sheng-Hsuan Tseng ◽  
Chuan Poh Lim ◽  
Qi Chen ◽  
Cheng Cai Tang ◽  
Sing Teang Kong ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
The Relationship

ABSTRACT Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC24. A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

scholarly journals Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

2013 ◽  
Vol 58 (1) ◽  
pp. 309-316 ◽  
Author(s):  
Michael N. Neely ◽  
Gilmer Youn ◽  
Brenda Jones ◽  
Roger W. Jelliffe ◽  
George L. Drusano ◽  
...  
Keyword(s):  
Renal Function ◽  
Trough Concentration ◽  
Pharmacokinetic Data ◽  
Full Model ◽  
Full Data ◽  
Time Curve ◽  
Data Set ◽  
Content Type ◽  
Vancomycin Trough ◽  
Trough Concentrations

ABSTRACTThe current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults withStaphylococcus aureusinfections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%;P= 0.0001) and 14% (7 to 19%;P< 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%;P= 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter.

scholarly journals Challenges of Vancomycin Dosing and Therapeutic Monitoring in Neonates

2020 ◽  
Vol 25 (6) ◽  
pp. 476-484
Author(s):  
Jennifer T. Pham
Keyword(s):  
Pediatric Patients ◽  
Late Onset ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Coagulase Negative Staphylococci ◽  
Optimal Dosing ◽  
Increased Risk ◽  
Dosing Regimens ◽  
Vancomycin Trough ◽  
Trough Concentrations

Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ≥400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ≥400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.

scholarly journals Vancomycin Therapeutic Drug Monitoring in Children: New Recommendations, Similar Challenges

2020 ◽  
Vol 25 (6) ◽  
pp. 472-475
Author(s):  
J. Chase McNeil ◽  
Sheldon L. Kaplan
Keyword(s):  
Infectious Diseases ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Kidney Injury ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Monitoring Strategies ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
American Society

The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists have recently published revised guidelines for the therapeutic monitoring of vancomycin. Previous iterations of the guideline largely focused on targeting vancomycin trough concentrations (VTCs) in the range of 15 to 20 mg/L for therapeutic efficacy. The revised guidelines shift the focus of therapeutic monitoring directly to AUC/MIC-based therapeutic monitoring for children, with a suggestion of a goal AUC/MIC 400 to 800. The primary hesitation in applying these recommendations to children stems from the absence of pediatric clinical data demonstrating correlations with clinical outcomes and either VTC or AUC and no benefit in other secondary outcomes (e.g., recurrence, duration of bacteremia). One can glean indirectly from this that such aggressive dosing and monitoring strategies are unnecessary to achieve therapeutic success in the majority of children with serious methicillin-resistant Staphylococcus aureus infections. Providers should carefully weigh the potential unknown benefits of targeting vancomycin AUC 400 to 800 mg*hr/L in children with the known risks of acute kidney injury associated with increasing the dose of vancomycin as well as the substantial time, effort, and costs of this process.

scholarly journals Prediction of steroid resistance and steroid dependence in nephrotic syndrome children

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Katarzyna Zaorska ◽  
Piotr Zawierucha ◽  
Monika Świerczewska ◽  
Danuta Ostalska-Nowicka ◽  
Jacek Zachwieja ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Multiple Logistic Regression Analysis ◽  
Kidney Injury ◽  
Steroid Resistance ◽  
Neural Network Approach ◽  
Steroid Resistant ◽  
Steroid Dependence ◽  
Steroid Dependent ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Steroid resistant (SR) nephrotic syndrome (NS) affects up to 30% of children and is responsible for fast progression to end stage renal disease. Currently there is no early prognostic marker of SR and studied candidate variants and parameters differ highly between distinct ethnic cohorts. Methods Here, we analyzed 11polymorphic variants, 6 mutations, SOCS3 promoter methylation and biochemical parameters as prognostic markers in a group of 124 Polish NS children (53 steroid resistant, 71 steroid sensitive including 31 steroid dependent) and 55 controls. We used single marker and multiple logistic regression analysis, accompanied by prediction modeling using neural network approach. Results We achieved 92% (AUC = 0.778) SR prediction for binomial and 63% for multinomial calculations, with the strongest predictors ABCB1 rs1922240, rs1045642 and rs2235048, CD73 rs9444348 and rs4431401, serum creatinine and unmethylated SOCS3 promoter region. Next, we achieved 80% (AUC = 0.720) in binomial and 63% in multinomial prediction of SD, with the strongest predictors ABCB1 rs1045642 and rs2235048. Haplotype analysis revealed CD73_AG to be associated with SR while ABCB1_AGT was associated with SR, SD and membranoproliferative pattern of kidney injury regardless the steroid response. Conclusions We achieved prediction of steroid resistance and, as a novelty, steroid dependence, based on early markers in NS children. Such predictions, prior to drug administration, could facilitate decision on a proper treatment and avoid diverse effects of high steroid doses.

Impact of Nursing Education on the Proportion of Appropriately Drawn Vancomycin Trough Concentrations

2016 ◽  
Vol 29 (5) ◽  
pp. 472-474 ◽  
Author(s):  
Lindsay K. Coleman ◽  
Ashley S. Wilson
Keyword(s):  
Nursing Education ◽  
Nursing Staff ◽  
Trough Concentration ◽  
Posttest Score ◽  
Further Education ◽  
Inpatient Setting ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
The Mean ◽  
The Impact

Background: Few studies have investigated the timing of vancomycin trough concentration collection in the inpatient setting. To date, there are no published studies on the impact of targeted nursing staff education on the appropriate timing of vancomycin trough concentration collection. Objective: To evaluate the impact of educational sessions on nursing staff knowledge regarding vancomycin and proper collection of troughs. Methods: The nursing staffs of 5 hospital units with a high volume of vancomycin usage were targeted for voluntary vancomycin educational sessions. Comprehension of the educational content was measured by a 5-question pre-/posteducation quiz. Vancomycin trough concentrations were evaluated during a 2-month period pre-/posteducation for appropriate timing of sample draw, defined as ≤45 minutes prior to the next scheduled vancomycin dose. Results: A total of 114 nurses participated in the education sessions. The mean pretest score was 3.91 and the mean posttest score was 4.89 ( P < .001). Preeducation, 69% of trough concentrations were collected appropriately. Posteducation, 74% of samples were collected within the 45-minute time frame ( P = .20). Conclusions: A significant increase in short-term comprehension regarding vancomycin was seen posteducation. There was a nonsignificant increase in appropriately timed trough concentration collection posteducation. Further education of nursing staffs may be necessary to lessen timing errors.

scholarly journals Geriatric syndromes are potential determinants of the medication adherence status in prevalent dialysis patients

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2122 ◽  
Author(s):  
Chia-Ter Chao ◽  
Jenq-Wen Huang ◽  
Keyword(s):  
Medication Adherence ◽  
Symptom Control ◽  
Multiple Logistic Regression Analysis ◽  
Chronic Dialysis ◽  
Geriatric Syndromes ◽  
Dialysis Patients ◽  
Validated Questionnaire ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Background.Geriatric syndromes (GS) exhibit high prevalence in patients with end-stage renal disease (ESRD) under chronic dialysis irrespective of age. We sought to determine whether GS influences medication adherence in ESRD patients.Methods.A prospective cohort of chronic dialysis patients was assembled. The presence of GS components, including frailty/prefrailty, polypharmacy, and malnutrition, were ascertained through a validated questionnaire, electronic records and chart abstraction, and laboratory tests. The severity of medication non-adherence was defined using the eight-item Morisky Medication Adherence Scale (MMAS). Multiple logistic regression analysis was performed targeting MMAS results and incorporating relevant clinical features and GS.Results.The prevalence of frailty/pre-frailty, polypharmacy, and hypoalbuminemia/ malnutrition among the enrolled participants was 66.7%, 94%, and 14%, respectively. The average MMAS scores in these dialysis patients were 2 ± 1.7 (range, 0–6), with only 15.7% exhibiting high medication adherence. Multiple regression analyses showed that the absence of frailty/pre-frailty (P= 0.01) were significantly associated with poorer medication adherence, while the presence of polypharmacy (P= 0.02) and lower serum albumin, a potential sign of malnutrition (P= 0.03), were associated with poor adherence in another model.Conclusion.This study is among the very few reports addressing GS and medication adherence, especially in ESRD patients. Interventions targeting frailty, polypharmacy, and malnutrition might potentially improve the medication non-adherence and symptom control in these pill-burdened patients.

scholarly journals Use of Body Surface Area for Dosing of Vancomycin

2019 ◽  
Vol 24 (4) ◽  
pp. 296-303
Author(s):  
Elizabeth L. Sawrey ◽  
Mary W. Subramanian ◽  
Kacy A. Ramirez ◽  
Brandy S. Snyder ◽  
Brittany B. Logston ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Surface Area ◽  
Body Surface ◽  
Pediatric Patients ◽  
Obese Patients ◽  
Dosing Regimen ◽  
Trough Serum ◽  
Dosing Regimens ◽  
Vancomycin Trough ◽  
Trough Concentrations

OBJECTIVES Vancomycin weight-based dosing regimens often fail to achieve therapeutic trough serum concentration in children ≤12 years of age and rigorous studies evaluating efficacy and safety of body surface area (BSA)–based dosing regimens have not been performed. We compared vancomycin trough serum concentrations in pediatric patients receiving a weight- or BSA-based dosing regimen. METHODS This was a single-center, retrospective study evaluating pediatric patients, ages 1 to 12 years, who received vancomycin from September 2012 to October 2015. Patients received a minimum of 3 consecutive doses at the same scheduled interval within a dosing regimen prior to a measured vancomycin serum trough concentration. The primary outcome was percentage of initial vancomycin trough concentrations ≥10 mg/L. The secondary outcomes were percentage of supratherapeutic, therapeutic, and subtherapeutic vancomycin serum concentration for all patients, including a subset of overweight and obese patients, and number of nephrotoxic occurrences. RESULTS BSA-based dosing regimens resulted in 50% of the initial vancomycin trough concentrations ≥ 10 mg/L compared with 17% for the weight-based dosing regimens (p &lt; 0.0001). No statistically significant differences were noted between the 2 dosing regimens for supratherapeutic, therapeutic, or subtherapeutic trough concentrations for all patients, and for the subset of overweight and obese patients. Nephrotoxic occurrences were noted in 7% of the weight-based dosing regimens compared with none in the BSA-based dosing regimens. CONCLUSIONS A BSA-based vancomycin dosing regimen resulted in significantly more initial vancomycin trough concentrations ≥10 mg/L and trended towards higher initial vancomycin trough concentrations without observable nephrotoxicity.

scholarly journals Therapeutic Drug Monitoring and Impact Indicator of Vancomycin Pharmacokinetics in Abdominal Cancer Patients complicated with Severe Infectious Disease

2019 ◽  
Author(s):  
Xiaowu Zhang ◽  
Yang Lyu ◽  
Donghao Wang
Keyword(s):  
Infectious Disease ◽  
Mechanical Ventilation ◽  
Cancer Patients ◽  
Trough Concentration ◽  
Therapeutic Drug ◽  
Target Concentration ◽  
Impact Indicator ◽  
Vancomycin Trough ◽  
Delayed Group ◽  
Trough Concentrations

Abstract Abstract Objective: This study was designed to investigate effectiveness of therapeutic drug monitoring (TDM) and impact indicator of vancomycin pharmacokinetics in abdominal cancer patients complicated with severe infectious disease. Methods: A total of 78 patients abdominal cancer patients complicated with severe infectious disease were included. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The patients were divided into early and delayed groups based on whether they achieve the target concentration. And clinical factors were compared between two groups. Results: The average initial therapeutic dose of vancomycin was 15.18±3.29 mg/kg (q12h). Ultimately, we collected 78 patient‘s trough concentrations data. The research revealed that the abdominal cancer patients complicated with severe infectious disease had significantly lower initial vancomycin trough concentrations (median [IQR]: 6.90[5.28-11.20] mg/L) compared with the recommended standard goal vancomycin trough concentration (10-15 or 15-20 mg/L). Multiple regression analysis revealed that Cys-C was the most important variable for vancomycin target trough achievement. We divided patients into early and delayed groups based on whether the initial trough concentration achieved standard goal trough concentration. Although the clinical outcomes were similar between two groups, the duration of mechanical ventilation in Early group was considerably shorter compared with group Delayed group (χ2=4.532; p < 0.05; Fig 1E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2=6.607; p < 0.05; Fig 1F) and vasoactive agent (χ2=6.106; p < 0.05; Fig 1D) was considerably shorter compared with group Delayed group. Conclusions: The steady-state initial vancomycin trough concentration was significantly reduced in abdominal cancer patients complicated with severe infectious disease. Higher initial dosage regimen is needed to ensure clinical effectiveness. The baseline Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage. Early attainment of target concentration significantly improved hemodynamic stability and reduced duration of mechanical ventilation.

Feasibility of serum Cystatin C for predicting Vancomycin concentration in abdominal cancer patients with severe infectious disease

2019 ◽  
Author(s):  
Xiaowu Zhang ◽  
Donghao Wang
Keyword(s):  
Infectious Disease ◽  
Mechanical Ventilation ◽  
Cancer Patients ◽  
Trough Concentration ◽  
Impact Indicator ◽  
Vasoactive Agent ◽  
Standard Dosage ◽  
Vancomycin Trough ◽  
Delayed Group ◽  
Trough Concentrations

Abstract Background: This study was designed to investigate the population pharmacokinetics and impact indicator of vancomycin in abdominal cancer patients complicated with severe infectious disease. Methods: A total of 78 patients abdominal cancer patients complicated with severe infectious disease were included. Vancomycin serum trough concentrations were measured using the fluorescence polarization immunoassay (FPIA) method. The patients were divided into early and delayed groups based on whether they achieve the target concentration. And clinical factors were compared between two groups.Results: The average initial therapeutic dose of vancomycin was 15.18±3.29 mg/kg (q12h). The research revealed that the abdominal cancer patients complicated with severe infectious disease had significantly lower initial vancomycin trough concentrations (median [IQR]: 6.90[5.28-11.20] mg/L). Multiple regression analysis revealed that Cys-C was the most important variable for vancomycin target trough achievement. The duration of mechanical ventilation in Early group was considerably shorter compared with group Delayed group (χ2=4.532; p < 0.05; Fig 1E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2=6.607; p < 0.05; Fig 1F) and vasoactive agent (χ2=6.106; p < 0.05; Fig 1D) was considerably shorter compared with group Delayed group. Conclusions: The steady-state initial vancomycin trough concentration was significantly reduced in abdominal cancer patients complicated with severe infectious disease. The baseline Cys-C level measured prior to administration of vancomycin is suggested to be the most suitable parameter to predict whether vancomycin trough concentration is up to standard dosage.

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