Prophylactic Antifungal Agents in Acute Myeloid Leukemia – MD Magazine

 
 
Yoav Golan, MD, MS, FIDSA, attending physician and associate professor of medicine at Tufts University School of Medicine, Boston, MA, compares the spectrum of activity of various antifungal agents and their important role in antifungal prophylaxis in acute myeloid leukemia (AML).
 
 
When it pertains to antifungal prophylaxis, of course, the very first crucial step is just what to choose, which antifungal we need to use. We already discussed several of the characteristics that would certainly make an antifungal attractive for prophylaxis availability as an oral agent, also as activity versus molds and not merely versus Candida.
 
One of the crucial and informative studies is a study that compared the usage of posaconazole as compared to others usually used antifungal prophylaxis itraconazole in AML patients that undergo chemotherapy including fluconazole. This study included patients that had AML or myelodysplastic syndrome, and were 13 years of age and older. In this study, patients were randomized to receive either posaconazole or fluconazole and were treated multiple times about cycles of neutropenia. vital endpoints in this study was overall mortality by the end of induction therapy for AML and occurrence of invasive fungal infections, and particularly invasive mold infections. The study showed that the group treated along with posaconazole had a lesser risk of invasive fungal infection and particularly lesser risk of invasive Aspergillosis. The study likewise showed that the all-induce mortality at the end of chemotherapy and after the end of antifungal prophylaxis was substantially lesser for this group of patients treated along with posaconazole.
 
Another antifungal that’s usually used for prophylaxis in the AML population is voriconazole. Voriconazole has actually activity versus Candida also as molds. There haven’t been clinical trials that prove to superiority of voriconazole over fluconazole or itraconazole, which are considered, in some centers, as standard prophylaxis. However, voriconazole is being used in lots of centers for this indication.
 
Many of the centers about the country, also as in lots of others countries, usage posaconazole for their high-risk patients, meaning those along with significant neutropenia that’s expected to last for much more compared to seven days. Over the past year-and-a-half or so, we have actually seen the addition of brand-new formulations of posaconazole to our armamentarium. In the past, we had posaconazole solution that would certainly be taken three times a day, and Among the shortcomings was the reasonable bioavailability of this agent. We now have actually a posaconazole pill that’s often provided as 300 mg as soon as daily. This pill, and the method it’s produced, has actually increased the bioavailability of posaconazole, allowing its administration just as soon as everyday and resulting in blood levels of posaconazole that are a lot greater compared to the blood levels obtained along with the prior formulation of solution. Along with that, we likewise enjoyed the addition of intravenous posaconazole that Can easily be provided to those patients that cannot ingest any type of pills due to significant mucositis or others reasons.
 
When deciding on an antifungal prophylactic agent, Along with effectiveness, one has actually to think about the cost of an agent. Of course, this criterion need to not stand by itself and has actually to be contrasted along with the potential incentive from the agent, and a cost-effectiveness need to be after that calculated. The question is not merely exactly how a lot we have actually to spend to obtain a pill, however whether the insurance covers it—which is the case along with the majority of antifungals including posaconazole—however very is it valuable to the patient and affordable? Does it have actually reasonable cost? As soon as looking at antifungal prophylaxis in general, one would certainly strongly argue that allowing a fungal infection to happen and treating a fungal infection—which needs prolonged admissions and the usage of rather costly antifungals for a rather long period of time—also as the consequences of those infections, will certainly clearly suggest from a cost-effectiveness perspective that prevention is the most effective method to go. And there are several studies that highlighted the attractive cost-effectiveness profile of antifungal strategies.
 
Of the available antifungal strategies, we have actually discussed, specifically, the reality that posaconazole showed superiority over others agents in a clinical trial of AML patients. however the question is Can easily we afford posaconazole? As soon as looking at the cost of posaconazole, including the cost of the newer formulations of posaconazole, again, as opposed to the cost of joining the hospital and the cost of a fungal infection, it comes to be right away clear that the everyday cost that’s measured by hundreds of dollars is contrasted along with thousands and tens of thousands of dollars that are invested in treating existing fungal infections. That leads to the conclusion that efficient antifungal therapies and antifungal therapies that have actually much better ability to stay clear of invasive antifungal infections have actually a potential of likewise being cost-efficient due to the fact that they reduce the cost of care overall.