# Improved Sixty-Day Mortality in Candidemia with Antifungal Treatment Within 72 Hours of Fever Onset: A Single-Center Retrospective Study in Rural Japan

## TL;DR

Starting antifungal treatment within 72 hours of fever improves survival in candidemia patients at a rural hospital in Japan.

## Contribution

Demonstrates the effectiveness of early antifungal treatment based on fever in resource-limited settings.

## Key findings

- Early antifungal treatment within 72 hours of fever onset was linked to improved 60-day survival.
- CVC use was an independent predictor of mortality in candidemia patients.
- Younger age was associated with better survival outcomes in candidemia cases.

## Abstract

Introduction: Prognostic factor investigations for candidemia have been conducted in large-scale facilities, leading to significant evidence, including early administration of echinocandin antifungal agents and removal of central venous catheters (CVCs). In departments that provide aggressive chemotherapy or transplantation, candidiasis markers are regularly evaluated, and preemptive treatments may be initiated. However, in resource-limited facilities, candidemia detection largely relies on vital signs like fever and blood cultures. This study assessed whether evidence from large-scale facilities applies to such settings. Additionally, while prior studies indicate that early antifungal treatment is based on positive blood cultures, no established criteria exist for early administration based on fever as an indicator. Methods: This study analyzed cases of candidemia from blood cultures at Fukui General Hospital (2014–2024). Patients aged 18 or older with at least one positive blood culture for Candida species and clinical signs of infection were included, while contamination cases were excluded. The patients were categorized into survival and death groups based on 60-day survival from fever onset. The variables collected included age, gender, duration from admission to fever onset, time from fever onset to blood culture collection and antifungal treatment initiation, antifungal treatment within 72 h, serum albumin levels, history of cancer, diabetes, empiric echinocandin treatment, CVC insertion, duration of CVC insertion until fever onset, use of total parenteral nutrition, broad-spectrum antibiotic use, and sequential organ failure assessment (SOFA) score. Fever was defined as a body temperature of 38.0 °C or higher, guiding blood culture collection. Results: Of 30 candidemia cases, 29 were analyzed. Survival was significantly associated with younger age (average 73.3 ± 13.3 vs. 83.1 ± 9.1 years, p = 0.038) and antifungal treatment within 72 h of fever onset (9 vs. 3, p = 0.025). CVC use was of marginal significance (8 vs. 13, p = 0.108). There was a significant difference in the duration (in days) of CVC insertion until fever onset (median [IQR]: 15.5 [11.75–19.5] vs. 30.0 [19.0–39.0], p = 0.027). Logistic regression identified early antifungal treatment (OR = 0.065, p = 0.035) and CVC use (OR = 21.8, p = 0.024) as independent predictors of mortality. Conclusions: Early antifungal treatment within 72 h of fever onset and CVC use were independent predictors of mortality in candidemia. The importance of early antifungal treatment was reaffirmed even in smaller facilities. The impact of CVC insertion on 60-day survival cannot be readily generalized due to the limited sample size. Further research is needed to clarify the impact of fever-based antifungal initiation and CVC use on 60-day survival.