Association of the clinical efficacy of vancomycin with the novel pharmacokinetic parameter area under the trough level (AUTL) in elderly patients with hospital-acquired pneumonia

Fukumori, Shiro; Tsuji, Yasuhiro; Mizoguchi, Akiko; Kasai, Hidefumi; Ishibashi, Tôru; Iwamura, Narumichi; To, Ho

doi:10.1111/jcpt.12399

Cited by 19 publications

(17 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recommended target range of 15‐20 mg/L for vancomycin Ctrough seems to be acceptable for controlling vancomycin exposure, although a value of approximately 11 mg/L was found as optimal and safer in elderly patients . Efficacy of vancomycin was associated with area under the trough level (AUTL), a novel pharmacokinetic parameter . Determining the target AUTL or Ctrough may enhance the efficacy of vancomycin therapy in elderly patients with MRSA pneumonia .…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

“…Efficacy of vancomycin was associated with area under the trough level (AUTL), a novel pharmacokinetic parameter . Determining the target AUTL or Ctrough may enhance the efficacy of vancomycin therapy in elderly patients with MRSA pneumonia . Given that nephrotoxicity may increase with a Ctrough >15 mg/L, this level should not be exceeded in this subpopulation.…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

See 1 more Smart Citation

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

Vancomycin is a fundamental antibiotic in the management of severe Gram‐positive infections. Inappropriate vancomycin dosing is associated with therapeutic failure, bacterial resistance and toxicity. Therapeutic drug monitoring (TDM) is acknowledged as an important part of the vancomycin therapy management, at least in specific patient subpopulations, but implementation in clinical practice has been difficult because there are no consensus and agglutinator documents. The aims of the present work are to present an overview of the current knowledge on vancomycin TDM and population pharmacokinetic (PPK) models relevant to specific patient subpopulations. Based on three published international guidelines (American, Japanese and Chinese) on vancomycin TDM and a bibliographic review on available PPK models for vancomycin in distinct subpopulations, an analysis of evidence was carried out and the current knowledge on this topic was summarized. The results of this work can be useful to redirect research efforts to address the detected knowledge gaps. Currently, TDM of vancomycin presents a moderate level of evidence and practical recommendations with great robustness in neonates, pediatric and patients with renal impairment. However, it is important to investigate in other subpopulations known to present altered vancomycin pharmacokinetics (eg neurosurgical, oncological and cystic fibrosis patients), where evidence is still unsufficient.

show abstract

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Monteiro

Hahn

Gonçalves

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

show abstract

“…Goal trough concentrations for adults are generally between 15 and 20 μg/mL, but may be higher or lower depending on infection, severity of illness, and clinical judgement [9]. In the elderly, new evidence suggests that troughs >15 μg/mL are associated with increased rates of nephrotoxicity, and should not be exceeded [79]. Clinicians should monitor elderly patients carefully, possibly accepting a lower trough concentration if clinical improvement is seen.…”

Section: Practical Applicationsmentioning

confidence: 99%

Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application

et al. 2016

View full text Add to dashboard Cite

The elderly population can be divided into three distinct age groups: 65–74 years (young-old), 75–84 years (middle-old), and 85+ years (old-old). Despite evidence of a shift in leading causes for mortality in the elderly from infectious diseases to chronic conditions, infections are still a serious cause of death in this population. These patients are at increased risk due to weakened immune systems, an increased prevalence of underlying comorbidities, and decreased physiologic reserves to fight infection. Additionally, elderly patients, especially adults in institutional settings, are at an increased risk of colonization and subsequent infection with methicillin-resistant Staphylococcus aureus at a rate that is five times higher than in younger individuals, causing an increase in empiric and definitive vancomycin use. Elderly patients have unique characteristics that make dosing vancomycin a challenge for clinicians, such as increased volume of distribution and decreased renal function. Using the best available evidence, it is recommended to initiate lower empiric maintenance doses and monitor vancomycin serum concentrations earlier than steady state to accurately calculate drug elimination and make appropriate dose adjustments.

show abstract

“…First, it questions whether AUC 24 /MIC is the optimal vancomycin pharmacokinetic–pharmacodynamic target. Fukumori’s group reported the area under the trough level as a novel pharmacokinetic–pharmacodynamic parameter that more strongly correlates with vancomycin clinical efficacy compared to AUC 24 [52]. Second, it suggests that cure may be more associated with the extent of consistency, sustainability and fluctuations of vancomycin exposure during the course of therapy, rather than a total single exposure estimate.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Al-Sulaiti

Nader

Saad

et al. 2019

Eur J Drug Metab Pharmacokinet

View full text Add to dashboard Cite

BackgroundVancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date.ObjectivesWe aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates.MethodsA multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations.ResultsSixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group.ConclusionMaintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.

show abstract

Association of the clinical efficacy of vancomycin with the novel pharmacokinetic parameter area under the trough level (AUTL) in elderly patients with hospital-acquired pneumonia

Cited by 19 publications

References 21 publications

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations

Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application

Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Contact Info

Product

Resources

About