Evaluation of Dosing Strategies and Trough Concentrations of Vancomycin in Patients Undergoing Continuous Venovenous Hemofiltration

2021 ◽  
Author(s):  
Krista A. Wahby ◽  
Lejla Cunmaljaj ◽  
Karim Mouabbi ◽  
Zinah Almadrahi ◽  
Liz Wilpula
Keyword(s):  
Continuous Venovenous Hemofiltration ◽  
Dosing Strategies ◽  
Trough Concentrations

scholarly journals Determinants of Ceftazidime Clearance by Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodialysis

2000 ◽  
Vol 44 (6) ◽  
pp. 1639-1644 ◽  
Author(s):  
Gary R. Matzke ◽  
Reginald F. Frye ◽  
Melanie S. Joy ◽  
Paul M. Palevsky
Keyword(s):  
Repeated Measures ◽  
High Performance ◽  
Mixed Model ◽  
Random Effect ◽  
Quantitative Information ◽  
Continuous Venovenous Hemofiltration ◽  
Linear Relationships ◽  
Repeated Measures Analysis ◽  
Continuous Venovenous Hemodialysis ◽  
Dosing Strategies

ABSTRACT Although several dosage adjustment regimens have been proposed, there is little quantitative information to guide the initiation of ceftazidime therapy in patients who are receiving continuous renal replacement therapy. To determine the clearance of ceftazidime by continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies with stable hemodialysis patients with three hemofilters: a 0.6-m2 acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m2 polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m2 polysulfone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intravenously prior to the start of a clearance study. The concentration of ceftazidime in multiple plasma and dialysate or ultrafiltrate samples was determined by high-performance liquid chromatography. The diffusional clearances (CIdiffusion) and sieving coefficients of ceftazidime were compared by a mixed-model repeated-measures analysis of variance with filter and blood, dialysate inflow, or ultrafiltration rate as the main effect and the patient as a random effect. The fraction of ceftazidime bound to plasma proteins was 17% ± 7% (range, 10 to 25%). The clearances of ceftazidime, urea, and creatinine by CVVHD were essentially constant at blood flow rates of 75 to 250 ml/min for all three filters. Significant linear relationships (P < 0.0001) were observed between CIdiffusion of ceftazidime and clearance of urea for all three filters: AN69 (slope = 0.83), PMMA (slope = 0.89), and PS (slope = 1.03). Ceftazidime clearance was membrane independent during CVVH and CVVHD. CVVH and CVVHD can significantly augment the clearance of ceftazidime. Dosing strategies for initiation of ceftazidime therapy in patients receiving CVVH and CVVHD are proposed.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity

2017 ◽  
Vol 51 (11) ◽  
pp. 937-944 ◽  
Author(s):  
Yookyung Christy Choi ◽  
Stephen Saw ◽  
Daniel Soliman ◽  
Angela L. Bingham ◽  
Laura Pontiggia ◽  
...  
Keyword(s):  
Concomitant Administration ◽  
Class I ◽  
Class Iii ◽  
Obesity Class ◽  
Class Iii Obesity ◽  
Dosing Strategies ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
Serum Vancomycin ◽  
Nonobese Patients

Background:A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. Objective: To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. Methods: This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m2), obesity class I and II (BMI 30-39.9kg/m2), and obesity class III (BMI≥40 kg/m2) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Results: Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Conclusions: Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

scholarly journals Effects of continuous venovenous hemofiltration on vancomycin trough concentrations in critically ill children

2021 ◽  
Vol 9 (3) ◽  
pp. 224-224
Author(s):  
Lengyue Peng ◽  
Yawen Gao ◽  
Guangli Zhang ◽  
Xiaoyin Tian ◽  
Huiting Xu ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Children ◽  
Continuous Venovenous Hemofiltration ◽  
Vancomycin Trough ◽  
Trough Concentrations

scholarly journals Evaluation of Posaconazole Dosing in Children and Young Adults: A Single-Center Review

2021 ◽  
Vol 26 (8) ◽  
pp. 834-840
Author(s):  
Lauren M. Garner ◽  
Susan Ngo ◽  
Jenna Bognaski Kaplan ◽  
William S. Wilson ◽  
Cameron J. McKinzie
Keyword(s):  
Pediatric Patients ◽  
Liver Function Tests ◽  
Current Data ◽  
Dosing Regimen ◽  
Drug Concentrations ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Dosing Strategy ◽  
Dose Modifications

OBJECTIVE Initial posaconazole dosing regimens in children often do not achieve target concentrations, and data continue to support the need for higher initial dosing regimens. The objective of this study is to contribute to the current data regarding suboptimal posaconazole dosing in pediatric patients by retrospectively observing dosing strategies and subsequent drug concentrations. METHODS This study was conducted at a single institution in 27 patients aged 1 to 21 years. Patients who were initiated on any formulation of posaconazole for prophylaxis or treatment while admitted to the hospital were included. The primary outcome was to determine the percentage of pediatric patients who achieved the targeted trough concentration using their initial posaconazole dosing regimen. Secondary outcomes included percentage of patients who experienced a breakthrough invasive fungal infection (IFI), percentage of patients with elevated liver function tests (LFTs), and discontinuation for any reason. RESULTS There were 15 patients (55.5%) who reached desired trough serum concentration after the initial dosing regimen. The number of dose modifications to achieve the desired trough ranged from 1 to 3. Most patients received delayed-release tablets (n = 17), and the average doses for reaching prophylactic and treatment trough concentrations were 6.1 mg/kg/day and 11 mg/kg/day, respectively. There were 2 patients (7.4%) who experienced breakthrough IFI. Overall, 5 patients developed elevated LFTs and 7 patients discontinued treatment early. CONCLUSIONS The results describe a single population of pediatric patients, of whom 55% were able to achieve target trough concentrations of posaconazole with the initial dosing strategy used.

scholarly journals Pharmacodynamic Target Attainment for Meropenem and Piperacillin/Tazobactam Using a PK/PD-based Dosing Calculator in Critically Ill Patients

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S27-S27 ◽  
Author(s):  
Emily Heil ◽  
David P Nicolau ◽  
Gwen Robinson ◽  
Andras Farkas ◽  
Kerri Thom
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Future Research ◽  
Target Attainment ◽  
Research Support ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Culture Positive ◽  
Antibiotic Dosing

Abstract Background Unbound plasma concentrations of β-lactam antibiotics vary widely and attainment of PK/PD targets is highly variable in critically ill patients, which may affect microbiologic cure or contribute to toxicity. PK/PD-based antibiotic dosing programs may provide more accurate doses that achieve predicted targets for a cultured organism. Methods This was a single center, prospective study of critically ill patients with culture positive gram-negative infections treated with meropenem (MEM) or piperacillin/tazobactam (TZP). A PK/PD-based antibiotic dosing app was used to select doses that had a probability of target attainment (PTA) of 90% or greater for time above MIC (fT&gt;MIC) of at least 40% for MEM and 50% for TZP. Total meropenem, piperacillin and tazobactam mid-point and trough concentrations were obtained at steady-state and adjusted for protein binding, to assess target attainment. Results Thirty-six patients were enrolled; 20 received MEM and 16 TZP. Antibiotic concentrations varied widely amongst patients, particularly with TZP. MEM and TZP concentrations are displayed in Table 1 and Figure 1. Doses evaluated for &gt;90% probability of target attainment in the dosing calculator differed from standard package labeled doses for 25% (5/20) of MEM and 18.8% (3/16) of TZP patients. All (20/20) MEM and 94% (15/16) TZP patients maintained fT&gt;MIC for the entire dosing interval. Conclusion A PK/PD based antibiotic dosing calculator that provides individualized β-lactam doses can lead to altered doses that may increase probability of target attainment in critically ill patients. Future research is needed to review the relevance of PK/PD-based dose adjustments on clinical outcomes. Disclosures D. P. Nicolau, Shionogi & Co.: Research Contractor, Research support; A. Farkas, Optimum Dosing Strategies: Employee, Salary.

scholarly journals Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

2012 ◽  
Vol 56 (12) ◽  
pp. 6181-6185 ◽  
Author(s):  
Erin N. Frazee ◽  
Philip J. Kuper ◽  
Garrett E. Schramm ◽  
Scott L. Larson ◽  
Kianoush B. Kashani ◽  
...  
Keyword(s):  
Critically Ill ◽  
Medical Center ◽  
Inverse Correlation ◽  
Continuous Venovenous Hemofiltration ◽  
Content Type ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
Clinically Significant ◽  
Dosing Strategy ◽  
Critically Ill Adults

ABSTRACTThe vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h;n= 10) or high (>30 ml/kg/h;n= 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low- and high-HFR individuals, respectively (P< 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r= −0.423;P< 0.001). In the subgroup of 14 methicillin-resistantStaphylococcus aureus(MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P= 0.516) and in culture-positive MRSA patients (P= 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.

scholarly journals An Evaluation of Initial Vancomycin Dosing in Infants, Children, and Adolescents

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Laura Broome ◽  
Tsz-Yin So
Keyword(s):  
Primary Outcome ◽  
Age Groups ◽  
Pediatric Age ◽  
Serum Trough ◽  
Hospital Patients ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Higher Doses ◽  
Retrospective Database

Background. The pharmacokinetics of many medications change as we age, thus most would assume dosing strategies would adjust for these changes. The objective of this study is to evaluate the initial vancomycin dosing in three pediatric age groups based on measured serum trough concentrations.Methodology. This retrospective database review included patients aged from 1 month to 18 years old admitted to the Moses H. Cone Memorial Hospital. Patients had to have received vancomycin dosed at 15 mg/kg every 8 hours with an appropriately measured trough concentration. The primary outcome was to determine the percentage of patients in 3 pediatric age groups achieving therapeutic trough concentrations with the initial vancomycin dosing regimen.Results. Twenty-five patients were included in the study. None of the patients had therapeutic trough concentrations after receiving vancomycin 15 mg/kg every 8 hours. Only one patient had a supratherapeutic level, while all of the other patients had levels less than 10 mcg/mL.Conclusions. Vancomycin 15 mg/kg every 8 hours did not provide therapeutic serum trough concentrations for any pediatric age groups. Higher doses and/or more frequent dosing regimens need to be evaluated for each age group to determine the most appropriate strategies for producing therapeutic trough concentrations.

scholarly journals Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin

2020 ◽  
Vol 75 (4) ◽  
pp. 1038-1046
Author(s):  
Nathan H Ma ◽  
Sandra A N Walker ◽  
Marion Elligsen ◽  
Alex Kiss ◽  
Lesley Palmay ◽  
...  
Keyword(s):  
Cohort Study ◽  
Continuous Infusion ◽  
Renal Injury ◽  
Intermittent Infusion ◽  
Matched Cohort ◽  
Lower Odds ◽  
Matched Cohort Study ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Dosing Strategy

Abstract Background Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15–20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking. Objectives To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities. Methods A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. Results Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21–0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05–0.59, P = 0.004). Conclusions CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require &gt;4 g/day to achieve therapeutic levels.

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