Abstract & Commentary
Systemic Antifungal Therapy in ICU Patients Without Documented Invasive Fungal Infection
By David J. Pierson, MD, Editor, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Editor for Critical Care Alert.
Synopsis: As shown by this large cross-sectional cohort study of critically ill patients, it remains unclear when systemic antifungal therapy should be used and which patients should receive it. Most of the patients receiving such therapy did not have invasive fungal infection, and in the majority of instances it was not given in accordance with current practice guidelines.
Source: Azoulay E, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med 2012;40:813-822.
Investigators representing three professional societies carried out a point-prevalence assessment of the use of systemic antifungal therapy (SAT) in patients in ICUs in France and Belgium on December 8, 2008. The goals were to determine how prevalent empirical SAT was in critically ill patients who did not have documented invasive fungal infection (IFI), and what demographic, clinical, and outcome variables correlated with this practice. Of 453 ICUs affiliated with two of the sponsoring societies, 169 (37%) participated in the study. In the participating ICUs, protocols for the use of antifungal agents were in place in 56%, and routine cultures for colonization were carried out in 90%; 16% of the units used antifungal prophylaxis.
Of the 2047 patients evaluated, 154 (7.5%) received SAT on the study day; 54 of these had a proven ISI and 100 (65%) did not. Agents used were fluconazole in 60%, caspofungin in 24%, voriconazole in 8%, and liposomal amphotericin B in 5% of patients. Patients were more likely to receive SAT if they were more severely ill, had severe sepsis, had undergone emergency surgery, had a diagnosis of malignancy, or were colonized with Candida species. SAT was also positively correlated with smaller hospital size, solid organ transplantation activity, a higher annual incidence of candidemia, the uncontrolled use of fluoroquinolones in the institution, and routine SAT in septic patients. When compared to patients who did not receive SAT, 28-day mortality (~ 20%) was no different in the patients who received SAT, despite their initially having been more severely ill. The authors suggest that because the patients receiving empirical SAT might have been predicted to have worse survival than patients who were not given SAT, the lack of a significant mortality difference might indicate a beneficial effect of the latter.
Commentary
This study found that 7.5% of all ICU patients were receiving SAT on the day of assessment, and that two-thirds of these did not have a documented IFI. Further, patients usually received SAT for reasons that were not listed in current guidelines. One might be tempted to conclude that SAT tends to be prescribed unnecessarily, but the situation is not so simple. In an accompanying editorial,1 Ostrosky-Zeichner points out that empirical SAT in critically ill patients is driven by two factors: our current far-from-perfect ability to diagnose IFI, and studies indicating that a delay of as little of 1-2 days in instituting appropriate antifungal therapy can make an important difference in patient outcome. It used to be that treating IFI meant using amphotericin B and incurring its attendant renal toxicity and other adverse effects. However, now that a number of substantially less-toxic agents are readily available, this obstacle to empirical therapy has been removed, a factor that doubtless has contributed to today's widespread use of SAT in patients without documented IFI.
This study was carried out in France and Belgium, and the participating ICUs had a higher prevalence of protocols for both surveillance fungal cultures and the use of antifungal therapy than may be present in American units. Thus, the findings may not be quantitatively applicable to the practice environment in the United States. Nonetheless, SAT is widely used, and often in patients deemed at high risk for ISI but without definite proof. Until evidence from clinical trials can better inform the decision making, this will likely remain an area influenced heavily by individual patient risk factors, local practice pReferences, and institutional policies.
Reference
- Ostrosky-Zeichner L. Systemic antifungal therapy in patients without documented invasive fungal infection: A peek into the world of empirical antifungal therapy. Crit Care Med 2012;40:997-998.
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