1570. Cumulative Antibiotic Exposure and Risk for Candidemia
Authors: Dougherty Jack , Turner Nicholas A , Yarrington Michael E , Shaefer Spires S , Moehring Rebekah W , Alexander Barbara D , Park Lawrence P , Johnson Melissa D 
Published: December 2022

Abstract

Background
Broad-spectrum antibiotic use is a known risk factor for candidemia, but the duration and type of antibiotic exposure associated with greatest risk are not well characterized. Measurements of antibiotic days may be useful to assess cumulative burden of selective pressure on the microbiome and risk for candidemia.

Methods
This retrospective cohort study aimed to quantify the effect of antibiotic exposure on risk for candidemia. The primary outcome was hazard for developing candidemia across an array of antibiotic agents, classes and spectra. We measured antibiotic days of therapy (DOT) for adults admitted to Duke University hospitals 1/1/2016–12/31/2021. We excluded patients with community-onset candidemia, defined as growth of Candida spp. in blood culture collected ≤ 48 hours of admission, because antibiotic exposure prior to arrival was not reliably accessible. Time-to-event analyses were performed using the Nelson-Aalen estimator for modeling cumulative hazard functions to compare the proportion of candidemia observed based on exposure to each antibiotic. Logrank tests were used to evaluate for differences between hazard functions with a pre-specified alpha level of 0.05, and exponential cumulative proportional hazards models were implemented to generalize hazard functions.

Results
During 164,185 encounters in 105,330 unique patients, we identified candidemia in 237 patients. Prior to developing candidemia, cases received a total of 9,604 antibacterial DOT distributed across 46 unique antibiotic agents (Fig. 1) Carbapenems were associated with increased hazard for candidemia compared to beta-lactams (p&lt; 0.005) (Figs. 2–3). There were 57 encounters for candidemia where meropenem was administered with a median of 10 DOT prior to onset of candidemia.
Days of Antibiotic Therapy by Agent and Outcome.

Conclusion
This work represents a novel approach to quantifying antibiotic exposure as a risk factor for candidemia. In an unadjusted model, we identified carbapenems as a high-risk class; additional analysis with adjusted regression models will help contextualize exposure risk with respect to comorbidity and illness severity. This work may serve as a reference for antibiotic stewards as they promote appropriate antibiotic use, including reducing overuse of broad-spectrum antibiotics.

Disclosures
Rebekah W. Moehring, MD, MPH, FIDSA, FSHEA, UpToDate, Inc.: Author Royalties Barbara D. Alexander, MD, Astellas: Advisor/Consultant|HealthtrackRx: Advisor/Consultant|HealthtrackRx: Grant/Research Support|Scynexis: Grant/Research Support|UpToDate: Advisor/Consultant Melissa D. Johnson, PharmD, Biomeme: Licensed Transcriptional Signature for Candidemia|Charles River Laboratories: Grant/Research Support|Entasis Therapeutics: Advisor/Consultant|Merck & Co. Inc: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Pfizer, Inc.: Advisor/Consultant|Scynexis Inc.: Grant/Research Support|Theratechnologies: Advisor/Consultant.