In this episode, I’ll discuss empiric vs pre-emptive antifungal therapy.
The current standard of care for high-risk neutropenic patients with persistent fever is to start empiric antifungal therapy. This is done because the potential of missing a fungal infection in such patients can be catastrophic, so some unnecessary antifungal usage is justified to avoid the excess mortality that would come with waiting for more objective signs of a fungal infection.
However there are diagnostic tests such as galactomannan that have the potential to narrow down which high-risk neutropenic patients with a fever are likely to benefit from antifungal therapy.
To explore this topic a group of researchers split 549 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients into two groups. The empiric therapy group was given casopfungin if they developed persistent fever, and the pre-emptive group was only given caspofungin if they met diagnostic screening criteria based on galactomannan (GM) screening and a chest CT-scan. It is not clear to me why the researchers called the second group the “pre-emptive” strategy as it more accurately could be called a diagnostic-driven approach.
This was a non-inferiority study and the primary endpoint was overall survival 42 days after randomization.
At day 42, overall survival of the diagnostic-driven approach was non-inferior to standard of care empiric therapy. Likewise, the rates of invasive fungal disease (IFD) by day 84 were not different between groups.
However, the rate of caspofungin use in the diagnostic-driven approach was only 27%, compared with 63% in the empiric therapy group.
The authors concluded:
The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.
Look for diagnostic criteria such as galactomannan to start playing a role in the initiation of antifungal therapy in some patients.
To access my free download area with 20 different resources to help you in your practice, go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.