161. Flucytosine Utilization and Dosing Practices at an Academic Medical Center

Abstract Background The typical dose of flucytosine is 25 mg/kg/dose every 6 hours for severe infections due to Candida and Cryptococcus. Many hospital protocols use ideal body weight (IBW) for initial dosing to achieve a goal peak serum concentration of 30-80 mcg/mL, but this is supported by very limited data. Our objective was to evaluate flucytosine dosing strategies, describe safety concerns, and explore financial benefits associated with using IBW. Methods All inpatient flucytosine orders for adults from 1/1/2015 through 10/31/2020 were retrospectively evaluated. Doses, weight used, flucytosine levels, adverse events, and potential cost savings associated with IBW dosing were characterized. Results During this period, 35 patients received flucytosine. The most common indications were cryptococcal meningitis (73%), pulmonary cryptococcosis (14%), and candidiasis (11%). Most patients were receiving concurrent liposomal amphotericin B (92%). Based on body mass index, most patients were overweight or obese (60%). Actual body weight was used for initial dosing in most cases (81%). Flucytosine peak monitoring was performed in 51% of cases. Initial peak levels were supratherapeutic in 10/19 cases (53%). Of those 10 patients, 70% were overweight/obese, and 60% would have received a lower initial dose if IBW had been used with dose rounding to the nearest 500mg capsule. Adverse events for all patients included new onset cytopenias, hepatic and renal dysfunction, occurring in 20%, 11%, and 60% respectively. Those with supratherapeutic levels had higher rates of new onset hepatic and renal dysfunction, 30% and 90% respectively. In 32% of cases, using IBW would have resulted in a lower daily dose, with an average dose reduction of 1888 mg, resulting in a mean cost savings per patient of &640/day using average wholesale price. Conclusion Most flucytosine orders were not dosed using IBW, which may have led to supratherapeutic levels. Using IBW for dosing in overweight patients may lead to reduced toxicity and potential cost savings. The default dosing weight for flucytosine in our electronic medical record will be set to IBW to encourage change. Disclosures Trevor C. Van Schooneveld, MD, FACP, BioFire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Insmed (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Rebiotix (Individual(s) Involved: Self): Scientific Research Study Investigator Bryan Alexander, PharmD, Astellas Pharma (Advisor or Review Panel member) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Grant/Research Support) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Individual(s) Involved: Self): Research Grant or Support

Background. The typical dose of flucytosine is 25 mg/kg/dose every 6 hours for severe infections due to Candida and Cryptococcus. Many hospital protocols use ideal body weight (IBW) for initial dosing to achieve a goal peak serum concentration of 30-80 mcg/mL, but this is supported by very limited data. Our objective was to evaluate flucytosine dosing strategies, describe safety concerns, and explore financial benefits associated with using IBW.
Methods. All inpatient flucytosine orders for adults from 1/1/2015 through 10/31/2020 were retrospectively evaluated. Doses, weight used, flucytosine levels, adverse events, and potential cost savings associated with IBW dosing were characterized.
Results. During this period, 35 patients received flucytosine. The most common indications were cryptococcal meningitis (73%), pulmonary cryptococcosis (14%), and candidiasis (11%). Most patients were receiving concurrent liposomal amphotericin B (92%). Based on body mass index, most patients were overweight or obese (60%). Actual body weight was used for initial dosing in most cases (81%). Flucytosine peak monitoring was performed in 51% of cases. Initial peak levels were supratherapeutic in 10/19 cases (53%). Of those 10 patients, 70% were overweight/obese, and 60% would have received a lower initial dose if IBW had been used with dose rounding to the nearest 500mg capsule. Adverse events for all patients included new onset cytopenias, hepatic and renal dysfunction, occurring in 20%, 11%, and 60% respectively. Those with supratherapeutic levels had higher rates of new onset hepatic and renal dysfunction, 30% and 90% respectively. In 32% of cases, using IBW would have resulted in a lower daily dose, with an average dose reduction of 1888 mg, resulting in a mean cost savings per patient of $640/day using average wholesale price.
Conclusion. Most flucytosine orders were not dosed using IBW, which may have led to supratherapeutic levels. Using IBW for dosing in overweight patients may lead to reduced toxicity and potential cost savings. The default dosing weight for flucytosine in our electronic medical record will be set to IBW to encourage change.
Disclosures Background. Antibiotic resistance is increasing worldwide, largely driven by excessive antibiotic use. Antibiotic stewardship (AS) interventions have traditionally focused on acute care, long-term care, and ambulatory settings. However, as patients transition from one care setting to another, AS interventions should address antibiotic orders (agent, dose, duration) between the hospital and the home. The purpose of this study is to determine the appropriateness of a total course of antibiotics, including inpatient and outpatient prescriptions, to aid in prioritizing AS interventions.
Methods. A single-center, retrospective study was performed to evaluate antibiotic duration for adult patients discharged from a large quaternary-care academic hospital. All antibiotic prescribing data, including pre-admission, during admission, and after hospital discharge, as well as information on indication, was collected from the electronic medical record. Descriptive statistics were used to summarize the data collected.
Results. 196 patients were included in the study. There were 100 instances of disagreement on antibiotic indication between the discharge summary and reviewer. However, 70% of patients were discharged on an appropriate antibiotic. The majority of patients (75%) were prescribed excess antibiotic days beyond guideline recommended total duration, and 68% of patients did not have appropriate duration of antibiotics post-discharge. Of those with excess duration, 31% were prescribed penicillins, 23% were prescribed cephalosporins, and 20% were prescribed trimethoprim/sulfamethoxazole. Excess antibiotic duration was associated most commonly with an unknown diagnosis (23%), a skin and soft tissue infection diagnosis (16%), and antibiotic prophylaxis (12%).
Conclusion. The results of this study showed that patients were often prescribed excess antibiotics at discharge, and the total duration of antibiotics from pre-admission to post-discharge were prolonged beyond guideline-recommended duration. Understanding the total duration of antibiotic prescription, including post-discharge and pre-admission durations, is key in assessing risk from antibiotics and targeting AS interventions.