Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock

Zelenitsky, Sheryl; Rubinstein, Ethan; Ariano, Robert E.; Iacovides, Harris; Dodek, Peter; Mirzanejad, Yazdan; Kumar, Anand

doi:10.1016/j.ijantimicag.2012.10.015

Cited by 103 publications

(74 citation statements)

References 29 publications

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“…It is widely accepted that the ratio of the area under the concentration-time curve (AUC) to MIC (AUC/MIC) is the best pharmacodynamic predictor of vancomycin efficacy, and a value !400 is associated with higher success rates in patients with respiratory tract infections [46] and bacteraemia [5] and !600 in patients with septic shock [47]. These data support the recent guidelines for vancomycin dosing [22] that recommend a trough serum concentration of !15 mg/L, supported by clinical data [48].…”

Section: Heteroresistancesupporting

confidence: 64%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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Section: Heteroresistancesupporting

confidence: 64%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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“…In a cohort of 182 patients with S. aureus bacteremia, an AUC/MIC ratio of Ͼ373 was identified as the breakpoint significantly associated with lower 30-day mortality (odds ratio [OR], 0.44) using the BMD method. Zelenitsky et al (21) found that, in a group of 35 patients with MRSA-associated septic shock, the survival rate was greater in those with higher AUC/MIC values, reaching 70% when the AUC/MIC ratio was Ն451 (P ϭ 0.006) and 81.8% when the AUC/MIC ratio was Ն578 (P ϭ 0.012). Nonetheless, these results should be interpreted with caution: the AUC was constructed with a population PK model using just one serum level determination, and a MIC of 1 mg/liter was assumed based on surveillance BMD data.…”

Section: Vancomycin Pharmacodynamics and Its Implications For Drug Momentioning

confidence: 99%

“…In clinical studies, an AUC/MIC ratio around 400 is related to the best survival rate or to clinical success in patients with S. aureus bacteremia, although other thresholds have been observed (10,17,18,21). In a cohort of 182 patients with S. aureus bacteremia, an AUC/MIC ratio of Ͼ373 was identified as the breakpoint significantly associated with lower 30-day mortality (odds ratio [OR], 0.44) using the BMD method.…”

Section: Vancomycin Pharmacodynamics and Its Implications For Drug Momentioning

confidence: 99%

Optimizing the Clinical Use of Vancomycin

Álvarez

López-Cortés

Molina

et al. 2016

Antimicrob Agents Chemother

190

124

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Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of >400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of >400 for a MIC of <1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated. Vancomycin has traditionally been used as a first-line agent for treating methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive beta-lactam-resistant bacteria (1), which are frequent etiologies of severe health-related infections (2, 3).Although the effectiveness of vancomycin is supported by more than 5 decades of use and multiple studies, the clinical and microbiological scenario in which it is used is always changing. Attaining an appropriate dosage of vancomycin for S. aureus infections might be difficult due to the clinical impact of the creep in the MIC of vancomycin and heteroresistance among MRSA strains, or due to complex pharmacokinetic and pharmacodynamic (PK/PD) situations. In this context, the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) introduced a practice guideline in 2009 (4), marking a milestone in vancomycin therapy. However, several questions, such as the optimal dosing in some special clinical situations (e.g., with renal replacement therapies or in burn patients or obese patients), the role of continuous infusion, or the renal toxicity when the suggested vancomycin serum levels are achieved, remain unanswered. The present review mainly focuses on these issues. VANCOMYCIN PHARMACODYNAMICS AND ITS IMPLICATIONS FOR DRUG MONITORINGThe killing effect of vancomycin is characterized by a slow mode of action and is further hampered by a large bacterial inoculum, a stationary growth phase, and anaerobic conditions (5, 6). Although several pharmacodynamic parameters have been proposed to determine vancomycin activity, data from experimental and clinical studies have selected the area under the curve (AUC)/ MIC ratio as the best parameter to predict the...

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“…Failure to achieve peak plasma targets on initial dosing has been associated with clinical failure with aminoglycosides [129]. Similarly, inadequate early vancomycin trough plasma concentrations (in relation to pathogen minimum inhibitory concentration [MIC]) have been associated with clinical failure for serious MRSA infections [130] (including nosocomial pneumonia [131] and septic shock [132].…”

mentioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock

Cited by 103 publications

References 29 publications

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Optimizing the Clinical Use of Vancomycin

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

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