Ryan Marko1, Julia Hajjar2, Vanessa Nzeribe3, Michelle Pittman4, Vincent Deslandes5, Nadia Sant5, Juthaporn Cowan5, Kwadwo Kyermentang5, Tim Ramsay6, Sheryl Zelenitsky7, Salmaan Kanji8. 1. , PharmD, is with The Ottawa Hospital, Ottawa, Ontario. 2. , MSc, is with The Ottawa Hospital, Ottawa, Ontario. 3. , BSc, is with The Ottawa Hospital, Ottawa, Ontario. 4. , BScPharm, is with The Ottawa Hospital, Ottawa, Ontario. 5. , MD, is with The Ottawa Hospital, Ottawa, Ontario. 6. , PhD, is with the Ottawa Hospital Research Institute, Ottawa, Ontario. 7. , PharmD, is with St. Boniface Hospital, Winnipeg, Manitoba. 8. , PharmD, is with The Ottawa Hospital and the Ottawa Hospital Research Institute, Ottawa, Ontario.
Abstract
BACKGROUND: Vancomycin remains widely used for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure rates up to 50% have been reported. At the authors' institution, monitoring of trough concentration is the standard of care for therapeutic drug monitoring of vancomycin. New guidelines support use of the ratio of 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) as the pharmacodynamic index most likely to predict outcomes in patients with MRSA-associated infections. OBJECTIVES: To determine the discordance rate between trough levels and AUC24/MIC values and how treatment failure and nephrotoxicity outcomes compare between those achieving and not achieving their pharmacodynamic targets. METHODS: This retrospective cohort study involved patients with MRSA bacteremia or pneumonia admitted to the study hospital between March 1, 2014, and December 31, 2018, and treated with vancomycin. Data for trough concentrations were collected, and minimum concentrations (C min) were extrapolated. The AUC24/MIC values were determined using validated population pharmacokinetic models. The C min and AUC24/MIC values were characterized as below, within, or above pharmacodynamic targets (15-20 mg/L and 400-600, respectively). Discordance was defined as any instance where a patient's paired C min and AUC24/MIC values fell in different ranges (i.e., below, within, or above) relative to the target ranges. Predictors of treatment failure and nephrotoxicity were determined using logistic regression. RESULTS: A total of 128 patients were included in the analyses. Of these, 73 (57%) received an initial vancomycin dose less than 15 mg/kg. The discordance rate between C min and AUC24/MIC values was 21% (27/128). Rates of treatment failure and nephrotoxicity were 34% (43/128) and 18% (23/128), respectively. No clinical variables were found to predict discordance. Logistic regression identified initiation of vancomycin after a positive culture result (odds ratio [OR] 4.41, 95% confidence interval [CI] 1.36-14.3) and achievement of target AUC24/MIC after 4 days (OR 3.48, 95% CI 1.39-8.70) as modifiable predictors of treatment failure. CONCLUSIONS: The relationship between vancomycin monitoring and outcome is likely confounded by inadequate empiric or initial dosing. Before any modification of practice with respect to vancomycin monitoring, empiric vancomycin dosing should be optimized. 2021 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.
BACKGROUND: Vancomycin remains widely used for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure rates up to 50% have been reported. At the authors' institution, monitoring of trough concentration is the standard of care for therapeutic drug monitoring of vancomycin. New guidelines support use of the ratio of 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) as the pharmacodynamic index most likely to predict outcomes in patients with MRSA-associated infections. OBJECTIVES: To determine the discordance rate between trough levels and AUC24/MIC values and how treatment failure and nephrotoxicity outcomes compare between those achieving and not achieving their pharmacodynamic targets. METHODS: This retrospective cohort study involved patients with MRSA bacteremia or pneumonia admitted to the study hospital between March 1, 2014, and December 31, 2018, and treated with vancomycin. Data for trough concentrations were collected, and minimum concentrations (C min) were extrapolated. The AUC24/MIC values were determined using validated population pharmacokinetic models. The C min and AUC24/MIC values were characterized as below, within, or above pharmacodynamic targets (15-20 mg/L and 400-600, respectively). Discordance was defined as any instance where a patient's paired C min and AUC24/MIC values fell in different ranges (i.e., below, within, or above) relative to the target ranges. Predictors of treatment failure and nephrotoxicity were determined using logistic regression. RESULTS: A total of 128 patients were included in the analyses. Of these, 73 (57%) received an initial vancomycin dose less than 15 mg/kg. The discordance rate between C min and AUC24/MIC values was 21% (27/128). Rates of treatment failure and nephrotoxicity were 34% (43/128) and 18% (23/128), respectively. No clinical variables were found to predict discordance. Logistic regression identified initiation of vancomycin after a positive culture result (odds ratio [OR] 4.41, 95% confidence interval [CI] 1.36-14.3) and achievement of target AUC24/MIC after 4 days (OR 3.48, 95% CI 1.39-8.70) as modifiable predictors of treatment failure. CONCLUSIONS: The relationship between vancomycin monitoring and outcome is likely confounded by inadequate empiric or initial dosing. Before any modification of practice with respect to vancomycin monitoring, empiric vancomycin dosing should be optimized. 2021 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.
Entities:
Keywords:
area under the concentration-time curve; methicillin-resistant Staphylococcus aureus; therapeutic drug monitoring; trough; vancomycin
Authors: Eric R Gregory; Donna R Burgess; Sarah E Cotner; Jeremy D VanHoose; Alexander H Flannery; Brian Gardner; Elizabeth B Autry; Derek W Forster; David S Burgess; Katie L Wallace Journal: J Pharm Pract Date: 2019-03-10
Authors: Emily L Heil; Kimberly C Claeys; Ryan P Mynatt; Teri L Hopkins; Karrine Brade; Ian Watt; Michael J Rybak; Jason M Pogue Journal: Am J Health Syst Pharm Date: 2018-10-17 Impact factor: 2.637