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Effectiveness and Safety of Empirical Antifungal Strategies in Critically Ill, Non-Neutropenic Patients: A
Shahad A Albakri1, Ahmad K Aljabri2, Emad A Alharbi2
1Pharmaceutical Care Department, King Fahad Hospital, Ministry of Health, Madinah, Saudi Arabia.
Introduction:
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in critically ill patients. While early empirical antifungal therapy (EAFT) is a common strategy to combat diagnostic delays, the choice of agent and its overall benefit remain debated. This study evaluates the clinical outcomes and safety profiles associated with different empirical antifungal strategies in non-neutropenic ICU patients with suspected IFIs.
Methods:
A retrospective observational study was conducted on 324 non-neutropenic patients who received EAFT in eight ICUs from 2015 to 2023. Data on demographics, comorbidities, treatments, and outcomes were collected from medical records. The primary endpoints were survival, clinical improvement, and incidence of confirmed fungal infection. Mortality predictors were identified using multivariate logistic regression.
Results:
Among the 324 patients, the overall in-hospital mortality rate was 78.70%. Mortality was significantly lower in the group receiving fluconazole (63.16%) compared to those receiving caspofungin (76.80%), liposomal amphotericin B (75%), and anidulafungin (84.83%) (p = 0.028). Regarding safety, fluconazole demonstrated the lowest incidence of hepatotoxicity (13.16%) and nephrotoxicity (7.89%). In contrast, anidulafungin was associated with the highest rate of hepatotoxicity (33.79%, p=0.035), and caspofungin was associated with the highest rate of nephrotoxicity (39.52%, p=0.003). Only 17.28% of patients achieved clinical improvement. After the initiation of EAFT, a fungal infection was confirmed in only 7.41% of patients.
Conclusion:
Fluconazole-based EAFT was associated with lower mortality rates compared to other antifungal agents. However, with a confirmed fungal infection rate of only 7.41%, these findings suggest that current patient selection for EAFT is suboptimal. The high overall mortality, coupled with the low infection confirmation rate, underscores the need for improved risk stratification tools to ensure the judicious use of antifungals in this critically ill population.
Insights
Early empirical antifungal therapy (EAFT) in critically ill patients showed fluconazole was linked to lower mortality. However, low confirmed fungal infection rates suggest suboptimal patient selection for EAFT.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pharmacology
Background:
- Invasive fungal infections (IFIs) contribute significantly to morbidity and mortality in critically ill patients.
- Early empirical antifungal therapy (EAFT) is frequently used to address diagnostic delays, but optimal agent selection and benefits are debated.
- Non-neutropenic ICU patients with suspected IFIs present a complex challenge for timely and effective treatment.
Purpose of the Study:
- To evaluate the clinical outcomes and safety of different empirical antifungal strategies in non-neutropenic ICU patients.
- To compare the efficacy of fluconazole, caspofungin, liposomal amphotericin B, and anidulafungin in this patient population.
- To identify predictors of mortality in critically ill patients receiving EAFT.
Main Methods:
- Retrospective observational study of 324 non-neutropenic patients receiving EAFT in ICUs (2015-2023).
- Data collection included demographics, comorbidities, treatments, and outcomes.
- Multivariate logistic regression was used to identify mortality predictors.
Main Results:
- Overall in-hospital mortality was 78.70%.
- Fluconazole was associated with significantly lower mortality (63.16%) compared to caspofungin (76.80%), liposomal amphotericin B (75%), and anidulafungin (84.83%) (p=0.028).
- Fluconazole showed the best safety profile regarding hepatotoxicity and nephrotoxicity; anidulafungin had the highest hepatotoxicity, and caspofungin the highest nephrotoxicity. Only 7.41% of patients had confirmed fungal infections.
Conclusions:
- Fluconazole-based EAFT demonstrated lower mortality rates in non-neutropenic ICU patients with suspected IFIs.
- The low rate of confirmed fungal infections (7.41%) indicates that current patient selection for EAFT may be suboptimal.
- Improved risk stratification tools are needed to optimize the use of antifungals in critically ill populations.
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