Association between Vancomycin Day 1 Exposure Profile and Outcomes among Patients with Methicillin-Resistant Staphylococcus aureus Infective Endocarditis

Casapao, Anthony M.; Lodise, Thomas P.; Davis, Susan L.; Claeys, Kimberly C; Kullar, Ravina; Levine, Donald P.; Rybak, Michael J.

doi:10.1128/aac.03970-14

Cited by 78 publications

(72 citation statements)

References 36 publications

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“…Notably, recent data suggests that higher total drug AUC:MIC values within the first 48 hours of therapy may be most associated with clinical outcome, with thresholds upwards of 600 ( f AUC:MIC ~300) being necessary. 168,169 Unfortunately, achievement of such high vancomycin exposures is likely limited to the most sensitive of isolates, as large dosing requirements produce high likelihoods of toxicity. 170,171 …”

Section: Antimicrobial Pharmacodynamicsmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Onufrak

Forrest

González

2016

Clinical Therapeutics

127

104

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Purpose An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with better-informed dosing regimens. Factors influential on antibiotic disposition and clinical outcome are presented, with a focus on the primary site of infection. Techniques to better understand antibiotic PK and optimize PD are acknowledged. Methods PubMed (inception – April 2016) was reviewed for relevant publications assessing antimicrobial exposures within different anatomical locations and clinical outcomes for various infection sites. Findings A limited literature base indicates variable penetration of antibiotics to different target sites of infection, with drug solubility and extent of protein binding providing significant PK influences in addition to the major clearing pathway of the agent. PD indices derived from in vitro and animal models determine the optimal magnitude and frequency of dosing regimens for patients. PK/PD modeling and simulation has been shown an efficient means of assessing these PD endpoints against a variety of PK determinants, clarifying the unique effects of infection site and patient characteristics to inform the adequacy of a given antibiotic regimen. Implications Appreciation of the PK properties of an antibiotic and its PD measure of efficacy can maximize the utility of these life-saving drugs. Unfortunately, clinical data remains limited for a number of infection site-antibiotic exposure relationships. Modeling and simulation can bridge preclinical and patient data for the prescription of optimal antibiotic dosing regimens, consistent with the tenets of personalized medicine.

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Section: Antimicrobial Pharmacodynamicsmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Onufrak

Forrest

González

2016

Clinical Therapeutics

127

104

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“…The likelihood of achieving good therapeutic levels decreases with higher MICs, increasing the risk of therapeutic failure. AUC/MIC ratios must also be computed from actual vancomycin daily doses, especially in the first 2 days of therapy [52,57].…”

Section: Vancomycinmentioning

confidence: 99%

Glycopeptide antibiotics: evolving resistance, pharmacology and adverse event profile

Henson

Levine

Wong

2015

Expert Review of Anti-infective Therapy

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The first glycopeptide antibiotic was vancomycin, isolated from the soil in the 1950s; since then, the class has expanded to include teicoplanin and the new semisynthetic glycopeptides dalbavancin, oritavancin and telavancin. They are bactericidal, active against most Gram-positive organisms, and in a concentration-dependent manner, inhibit cell wall synthesis. Resistance to vancomycin has emerged, especially among enterococci and Staphylococcus aureus through a variety of mechanisms. This emerging resistance to vancomycin makes proper dosing and monitoring of the area under the curve/MIC critically important. The chief adverse effect of vancomycin is nephrotoxicity, which is also intricately related to its dose. The efficacy of the semisynthetic glycopeptides has been demonstrated in skin and soft-tissue infections, but remains to be seen in serious methicillin-resistant Staphylococcus aureus infections.

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“…This may explain why many studies evaluating vancomycin exposure-response relationships demonstrate that AUC 24 thresholds are associated with improved outcomes in patients with serious methicillin-resistant Staphylococcus aureus infections, while data demonstrating the same effect with trough concentrations of Ͼ15 mg/liter are generally lacking (1,(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

Finch

Zasowski

Murray

et al. 2017

Antimicrob Agents Chemother

Self Cite

197

180

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Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of Ն400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P ϭ 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P ϭ 0.002). AUCguided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

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Association between Vancomycin Day 1 Exposure Profile and Outcomes among Patients with Methicillin-Resistant Staphylococcus aureus Infective Endocarditis

Cited by 78 publications

References 36 publications

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing

Glycopeptide antibiotics: evolving resistance, pharmacology and adverse event profile

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

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