Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration

2009 ◽  
Vol 44 (9) ◽  
pp. 751-765 ◽  
Author(s):  
C. Andrew Deryke ◽  
Donald P. Alexander
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Serum Concentration ◽  
Clinical Outcomes ◽  
Inhibitory Concentration ◽  
Health Care Systems ◽  
Time Curve ◽  
Concentration Time ◽  
Trough Serum Concentration ◽  
Trough Serum

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within one's own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

scholarly journals Successful Treatment of Invasive MRSA Infections in Children Using Area Under the Vancomycin Concentration-Time Curve Divided by the Minimum Inhibitory Concentration (AUC/MIC) to Measure Vancomycin Exposure

2021 ◽  
Vol 1 (S1) ◽  
pp. s31-s31
Author(s):  
Leslie Chiang ◽  
Alice Pong ◽  
John Bradley ◽  
Paige Anderson ◽  
William Murray
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Clinical Outcomes ◽  
Inhibitory Concentration ◽  
Renal Toxicity ◽  
Time Curve ◽  
Vancomycin Concentration ◽  
Concentration Time ◽  
Serum Trough ◽  
Trough Concentrations ◽  
Dosing Method

Background: Vancomycin is the treatment of choice for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous guidelines issued by the Infectious Diseases Society of America (IDSA) recommended targeting vancomycin serum trough concentrations of 15–20 mg/L; however, troughs <15 mg/L are also associated with increased odds of renal toxicity. To minimize toxicity, recently updated ASHP/IDSA/PIDS vancomycin dosing guidelines recommend the use of an area under the vancomycin concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC) pharmacodynamic index to measure vancomycin exposure, with an AUC/MIC ratio >400 correlating with clinical efficacy. However, data on vancomycin therapeutic drug monitoring (TDM) in children are limited. Our institutional practice since January 2009 has been to use AUC/MIC, rather than serum trough concentrations, to guide vancomycin dosing. In this study, we describe clinical outcomes in vancomycin-treated children with invasive MRSA infections using this dosing method. Methods: We performed a retrospective chart review of children hospitalized with invasive MRSA infections between 2006 and 2019 at Rady Children’s Hospital in San Diego, California. Clinical, microbiologic, and pharmacologic data including the site of MRSA infection, clinical failure or cure, occurrence of acute kidney injury (AKI), vancomycin MIC, vancomycin AUC, and serum trough concentrations were collected. Results: In total, 61 invasive MRSA cases were reviewed: 20 were admitted January 2016 through December 2008, and 41 were admitted January 2009 through June 2019 (Figure 1). Most patients did not have medical comorbidities. The most common types of infections were primary bacteremia (34%) and osteomyelitis (32%). Of 61 children, 50 (82%) had positive clinical outcomes regardless of vancomycin dosing method. Of 20 patients, 8 (40%) admitted prior to January 2009 developed AKI, compared with 5 (12%) of 41 patients admitted after January 2009. Conclusions: In our retrospective review, most patients had clinically successful outcomes regardless of which dosing strategy was used. We found higher rates of renal toxicity in patients who were admitted prior to 2009, with TDM based on measuring peak and trough concentrations, compared with those using AUC/MIC for TDM. Our findings suggest that AUC/MIC TDM for invasive MRSA infections may be associated with lower rates of renal toxicity.Funding: NoDisclosures: None

scholarly journals Development of a Population Pharmacokinetic Model for Parecoxib and Its Active Metabolite Valdecoxib after Parenteral Parecoxib Administration in Children

2012 ◽  
Vol 116 (5) ◽  
pp. 1124-1133 ◽  
Author(s):  
Bruce Hullett ◽  
Sam Salman ◽  
Sean J. O'Halloran ◽  
Deborah Peirce ◽  
Kylie Davies ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Pharmacokinetic Model ◽  
Inhibitory Concentration ◽  
Prediction Interval ◽  
Cyclooxygenase 2 ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Concentration Time

Background Parecoxib is a cyclooxygenase-2 selective inhibitor used in management of postoperative pain in adults. This study aimed to provide pediatric pharmacokinetic information for parecoxib and its active metabolite valdecoxib. Methods Thirty-eight children undergoing surgery received parecoxib (1 mg/kg IV to a maximum of 40 mg) at induction of anesthesia, and plasma samples were collected for drug measurement. Population pharmacokinetic parameters were estimated using nonlinear mixed effects modeling. Area under the valdecoxib concentration-time curve and time above cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib were simulated. Results A three-compartment model best represented parecoxib disposition, whereas one compartment was adequate for valdecoxib. Age was linearly correlated with parecoxib clearance (5.0% increase/yr). There was a sigmoid relationship between age and both valdecoxib clearance and distribution volume. Time to 50% maturation was 87 weeks postmenstrual age for both. In simulations using allometric-based doses the 90% prediction interval of valdecoxib concentration-time curve in children 2-12.7 yr included the mean for adults given 40 mg parecoxib IV. Simulated free valdecoxib plasma concentration remained above the in vitro 50% inhibitory concentrations for more than 12 h. In children younger than 2 yr, a dose reduction is likely required due to ongoing metabolic maturation. Conclusions The final pharmacokinetic model gave a robust representation of parecoxib and valdecoxib disposition. Area under the valdecoxib concentration-time curve was similar to that in adults (40 mg), and simulated free valdecoxib concentration was above the cyclooxygenase-2 in vitro 50% inhibitory concentration for free valdecoxib for at least 12 h.

scholarly journals Evaluation of Vancomycin Use in Late-Onset Neonatal Sepsis Using the Area Under the Concentration–Time Curve to the Minimum Inhibitory Concentration ≥400 Target

2015 ◽  
Vol 37 (6) ◽  
pp. 756-765 ◽  
Author(s):  
Jiraganya Bhongsatiern (JJ) ◽  
Chris Stockmann ◽  
Jessica K. Roberts ◽  
Tian Yu ◽  
Kent E. Korgenski ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Neonatal Sepsis ◽  
Inhibitory Concentration ◽  
Late Onset ◽  
Time Curve ◽  
Concentration Time

Should the Vancomycin Minimal Inhibitory Concentration be used as an Infant Critical Care Regular Criteria?

2020 ◽  
Vol 21 (11) ◽  
pp. 1052-1058
Author(s):  
Nadielle S. Bidu ◽  
Bruno J.D. Fernandes ◽  
Jucelino N.C. Filho ◽  
Regina E.A. Bastos ◽  
Joice N.R. Pedreira ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Minimal Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Therapeutic Monitoring ◽  
Therapeutic Window ◽  
Serum Concentrations ◽  
Concentration Data ◽  
Therapeutic Success ◽  
Trough Serum Concentration ◽  
Trough Serum

Background: Vancomycin is the first-line antibiotic used for the treatment of staphylococcal infections. Because of its narrow therapeutic window and the pharmacokinetics variability, vancomycin trough serum concentration should be monitored. However, due to the increased cases of staphylococcus’ commensal species infections and the case of vancomycin resistance, the minimal inhibitory concentration should be considered on antimicrobial therapy. Objective: This article aimed to show the importance of the minimal inhibitory concentration to infants on vancomycin therapy as regular criteria. Materials and Methods: Three infants in the use of vancomycin, hospitalized in the same maternity hospital, and that had at least one blood culture performed during the intensive-care-unit hospitalization were included in the study. Vancomycin serum concentrations were determined by particleenhanced- turbidimetric inhibition-immunoassay. The vancomycin minimal inhibitory concentration data were interpreted by following the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The trough serum concentration range of 10 to 20 mg.L-1 was considered therapeutic. Results: All three patients had at least one infection by S. epidermidis, being one patient exhibit vancomycin- resistant S. epidermidis infection. All patients had stoppages in the vancomycin treatment, and the minimal inhibitory concentration was performed for only one patient. Conclusion: The data obtained from these patients also showed the need to perform therapeutic monitoring by using minimal inhibitory concentration values, because, although the serum concentrations were within the reference range, they are insufficient to guarantee patient therapeutic success.

In Vitro Antibacterial activity of ethanolic extract of Myrsine africana against laboratory Strains of Pathogenic Organisms

2016 ◽  
Vol 5 (04) ◽  
pp. 4512
Author(s):  
Jackie K. Obey ◽  
Anthoney Swamy T* ◽  
Lasiti Timothy ◽  
Makani Rachel
Keyword(s):  
Antibacterial Activity ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
E Coli ◽  
Zones Of Inhibition ◽  
In Vitro Antibacterial Activity ◽  
Myrsine Africana

The determination of the antibacterial activity (zone of inhibition) and minimum inhibitory concentration of medicinal plants a crucial step in drug development. In this study, the antibacterial activity and minimum inhibitory concentration of the ethanol extract of Myrsine africana were determined for Escherichia coli, Bacillus cereus, Staphylococcus epidermidis and Streptococcus pneumoniae. The zones of inhibition (mm±S.E) of 500mg/ml of M. africana ethanol extract were 22.00± 0.00 for E. coli,20.33 ±0.33 for B. cereus,25.00± 0.00 for S. epidermidis and 18. 17±0.17 for S. pneumoniae. The minimum inhibitory concentration(MIC) is the minimum dose required to inhibit growth a microorganism. Upon further double dilution of the 500mg/ml of M. africana extract, MIC was obtained for each organism. The MIC for E. coli, B. cereus, S. epidermidis and S. pneumoniae were 7.81mg/ml, 7.81mg/ml, 15.63mg/ml and 15.63mg/ml respectively. Crude extracts are considered active when they inhibit microorganisms with zones of inhibition of 8mm and above. Therefore, this study has shown that the ethanol extract of M. africana can control the growth of the four organisms tested.

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