Impact of Duration and Spectrum of Antibiotic Exposure on Risk for Hospital-onset Candidemia

Background: Numerous studies have found broad-spectrum antibiotic exposure to be a risk factor for invasive candidiasis, but the risk of candidemia across the spectrum of antibiotic activity and duration of therapy is not well-defined. This retrospective study aims to characterize the hazard for candidemia with respect to depth and breadth of antibiotic exposure among hospitalized adults.

Methods: In this retrospective cohort study of adults admitted to a three-hospital health system from 2016 to 2021, we assessed the impact of duration and spectrum of antibiotic exposure as a risk factor for development of hospital-onset candidemia. Days of antibiotic spectrum coverage for groups of antibiotics were determined using an antimicrobial spectrum index. A proportional hazard regression model was constructed to contextualize the impact of antibiotic exposure among other established risk factors for invasive candidiasis.

Results: Over 1.2 million days of antibiotic therapy were administered across 162,913 hospital admissions, which included 236 episodes of hospital-onset candidemia. Broad-spectrum antibiotic administration was associated with increased hazard for candidemia in univariable analysis only. Among patients who developed candidemia, broader antibiotic exposure was associated with earlier-onset candidemia, and these patients had high rates of comorbidity and severe illness. In multivariable analysis, neutropenia, shock, total parenteral nutrition use, cirrhosis, and acute renal failure, but not broad-spectrum antibiotics, were associated with increased hazard for candidemia.

Conclusions: Numerous prior studies have associated broad-spectrum antibiotic use with risk for invasive candidiasis. In this large cohort of hospitalized adults with high rates of antibiotic exposure, we did not find an association between duration/spectrum of antibiotic exposure and risk for hospital-onset candidemia when controlling for other risk factors. Further study is warranted to assess the impact of dysbiosis on the risk of invasive candidiasis.