Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: a secondary analysis using a retrospective observational data

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.

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Vancomycin Trough Concentration Poorly Characterizes AUC: Is It Time to Transition to AUC-Based Vancomycin Monitoring?

Annals of Pharmacotherapy ◽

10.1177/1060028017716469 ◽

2017 ◽

Vol 51 (10) ◽

pp. 926-927 ◽

Cited By ~ 6

Author(s):

Robert W. Seabury ◽

Andrew M. Stoessel ◽

Jeffrey M. Steele

Keyword(s):

Trough Concentration ◽

Vancomycin Trough

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Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01653-13 ◽

2013 ◽

Vol 58 (1) ◽

pp. 309-316 ◽

Cited By ~ 179

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.

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Association of Vancomycin Trough Concentration With Response to Treatment for Acute Pulmonary Exacerbation of Cystic Fibrosis

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/pix043 ◽

2017 ◽

Vol 6 (3) ◽

pp. e103-e108 ◽

Cited By ~ 5

Author(s):

Nicholas M Fusco ◽

Richard Francisconi ◽

Calvin J Meaney ◽

Desiree Duman ◽

Carla A Frederick ◽

...

Keyword(s):

Cystic Fibrosis ◽

Trough Concentration ◽

Response To Treatment ◽

Pulmonary Exacerbation ◽

Vancomycin Trough

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Use of Individual Pharmacokinetics to Improve Time to Therapeutic Vancomycin Trough in Pediatric Oncology Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.2.92 ◽

2018 ◽

Vol 23 (2) ◽

pp. 92-99 ◽

Cited By ~ 2

Author(s):

Calvin L. Miller ◽

S. Alexander Winans ◽

John J. Veillette ◽

Steven C. Forland

Keyword(s):

Pediatric Oncology ◽

Trough Concentration ◽

Drug Clearance ◽

Patient Specific ◽

Pharmacokinetic Parameters ◽

Oncology Patients ◽

Number Of Patients ◽

Loma Linda University ◽

Vancomycin Trough ◽

The Impact

OBJECTIVE Optimization of vancomycin dosing is difficult in children, given rapid drug clearance and patient heterogeneity. We sought to evaluate the impact of dosing using individual pharmacokinetic parameters on time to goal trough concentration in pediatric oncology patients. METHODS A retrospective review was conducted to assess vancomycin dosing in the pediatric oncology unit at Loma Linda University Children's Hospital between January 2013 and August 2013 (standard dosing group [SDG]). These patients were compared to those in a prospective arm that used pharmacokinetic dosing (pharmacokinetic dosing group [PKG]) between March 2014 and May 2015. Outcomes included percent of patients reaching a target trough by the specified time points, number of dose adjustments, number of serum concentrations drawn, and number of patients with supratherapeutic troughs. RESULTS Of 35 patients meeting inclusion criteria for the SDG, 2 (5.7%) reached goal trough concentration by 48 hours, compared with 14 of 16 patients (87%) in the PKG (p = 0.0001). Significantly more patients reached their goal trough at each time point in the PKG. There was no difference in number of dose adjustments, but significantly more concentrations were drawn on average in the PKG (mean, 4.6 versus 3.1, p = 0.02). In the SDG and PKG, respectively, 1 patient and 3 patients had supratherapeutic trough concentrations (p = 0.09). CONCLUSIONS Dosing using individual pharmacokinetic parameters led to a significant reduction in time to attain the desired vancomycin trough concentration in our pediatric oncology patients. Given the wide variation in dose requirements in this and other studies, application of patient-specific pharmacokinetics is essential to optimize vancomycin dosing in pediatric patients.

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Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species

BMC Infectious Diseases ◽

10.1186/s12879-021-06809-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yujin Sohn ◽

John Hoon Rim ◽

Yunsuk Cho ◽

Jonghoon Hyun ◽

Yaejee Baek ◽

...

Keyword(s):

Treatment Outcome ◽

Trough Concentration ◽

Bacterial Infections ◽

Trough Level ◽

Cohort Analysis ◽

Univariate Analysis ◽

Area Under The Curve ◽

All Cause Mortality ◽

Vancomycin Trough ◽

Enterococcal Bacteremia

Abstract Background Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. Methods A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. Results A total of 37 patients were enrolled—26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. Conclusions In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

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