(250) Dosing and therapeutic drug monitoring of intravenous vancomycin in cystic fibrosis: A practice survey

Background: If a cystic fibrosis (CF) exacerbation warrants IV antibiotics, vancomycin is first-line for methicillin-resistant Staphylococcus aureus infection. Trough-based therapeutic drug monitoring (TDM) of vancomycin has been used historically, but revised consensus guidelines recommend area under the curve to minimum inhibitory concentration ratio (AUC/MIC)-based TDM.[1] The primary objective of this study was to assess pharmacists’ vancomycin dosing and TDM practices in people with CF (pwCF). A secondary objective was to evaluate AUC/MIC-based TDM implementation strategies.

Methods: An electronic survey was emailed via the CF Foundation Pharmacist listserv to pharmacists affiliated with CF centres on May 4^th, 2021; the survey closed June 17^th, 2021.

Results: Twenty eight pharmacists completed the survey: 71% cared for pediatrics with CF and 36% cared for adults with CF (Table 1). A specific resource, guideline, or nomogram was used by 71% for vancomycin dosing. Most (61%) never used a loading dose (LD). A LD was used ‘Sometimes’ and ‘Always’ by 29% and 11% of respondents, respectively. LD ranged from 20-30mg/kg in adults and 15-25mg/kg in pediatrics. Maximum total daily dose (TDD) was used by 28% of respondents; 4000mg was most common. Trough level was used in 75% and 79% for in- and outpatients, respectively. For adults, 56% targeted 15-20mg/L and 22% targeted 10-15mg/L. For pediatrics, 33% targeted 15-20mg/L and 39% targeted 10-15mg/L. For 3 respondents using peak levels, 35-40mg/L was targeted. AUC/MIC was used in 39% and 21% for in- and outpatients, respectively. Of 11 respondents, 91% targeted an AUC of 400-600mg•h/L. Pharmacist-led education sessions and protocol implementation facilitated the change to AUC/MIC-based TDM; challenges faced were appropriate level timing and AUC/MIC calculation, and staff education. Advantages of AUC/MIC-based TDM included lower vancomycin TDD, less toxicity, and fewer repeat levels needed; no decrease in effectiveness was observed. Common considerations for TDM included: local standard of practice (93%), evidence-based recommendations (61%), personal and/or healthcare team preference (46%), number of vancomycin levels required (43%), and availability of specific software (32%). Of 17 respondents using trough levels, 41% were planning/considering a change to AUC/MIC-based TDM.

Conclusions: Vancomycin dosing and TDM varies between pharmacists caring for pwCF. Since the practice survey conducted in 2015,[2] the proportion of respondents using trough-based vancomycin TDM has decreased, while the proportion using AUC/MIC-based TDM has increased. As well, the proportion of respondents targeting troughs of 15-20mg/L and 10-15mg/L has decreased and increased, respectively. Advantages with AUC/MIC-based TDM have been observed; adequate staff education and strategies to overcome barriers are necessary to implement this practice.

Acknowledgements:

References: 1. Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm. 2020;77(11):835-64.

2. Pettit RS, Peters SJ, McDade EJ, Kreilein K, Patel R, Epps K, et al. Vancomycin dosing and monitoring in the treatment cystic fibrosis: Results of a national practice survey. J Pediatr Pharmacol Ther. 2017;22:406-11.