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The Use of Combination Antifungal Therapy is Not a Black and White Issue

Infectious disease thinking means starting with a treatment having activity to the target fungi with the option of changing the class of drug if necessary, beginning treatment early, and being aware of co-morbidities.

When faced with a breakthrough mold infection, considering combination therapy can be prudent. The odds are that the offending mold is more resistant and/or virulent. Prompt action is needed, as breakthrough does not bode well for the patient’s prognosis. And, combination therapy can be less toxic than higher doses of 1 drug. “In the optimal scenario, a cautious early pre-emptive use of combination therapy with early re-evaluation seems the most logical and theoretically plausible in real-life,” said Dr. Kontoyiannis.

“I’m not really against combination therapy. And I agree that the clinical data does not reflect real-life. I have done thousands of clinical consults and no 2 have ever been the same. Yet, we have created homogenized patient populations, which makes if very challenging to gain insights on therapy in the face of such variability,” said Lindsey Baden, MD; Infectious Disease, Brigham & Women's Hospital, Boston, Massachusetts.

Gleaning insights from the existing data—knowing that it has largely been based on homogeneous patient populations—that can be fruitfully applied to the decidedly non-homogeneous patients who are a fact of everyday life is challenging. Nonetheless, some important information can be gleaned. Acting sooner rather than later is best. Using more drug is not necessarily good, as that can breed toxicity.

Given these considerations, Dr. Baden argued that combination therapy may have a role to play. “It can manage diagnostic uncertainty and lessen the concern for antifungal resistance. The lower dose of agents can minimize toxicity or shorten the antimicrobial course. And synergistic activity can improve clinical outcome, although there is very limited in vivo data,” said Dr. Baden. On the other hand, potential harms of the combination approach include drug antagonism or interaction, and increased treatment cost.

It is worth considering what we are trying to achieve with combination therapy, according to Dr. Baden. A current treatment like azole-based treatment has a success rate of 60%-80%. That may be near the top end, given that there always be some patients for whom treatment fails. “We have about a 10%-20% margin to work with. So, a 30%-50% relative benefit of combination therapy means an approximately 3%-10% absolute benefit in a very noisy model,” he explained.

Dr. Baden also stressed the need to remember that treating a fungal disease means treating the underlying reason for the disease, not just the disease itself. Initiatives directed at aspects including nutrition and other co-morbid conditions can pay off in terms of future infections.
Dimitrios P. Kontoyiannis: Pfizer: Research Contractor, Research support, and Speaker honorarium; Astellas: Research Contractor, Research support and Speaker honorarium; Merck: Honorarium, Speaker honorarium; Cidara: Honorarium, Speaker honorarium; Amplyx: Honorarium, Speaker honorarium; F2G: Honorarium, Speaker honorarium
Lindsey Baden: none


MEET-THE-PROFESSOR SESSION Combination Antifungal Treatment for Mold Infections: Pros and Cons
Combination Antifungal Treatment for Mold Infections: Pros
Dimitrios P. Kontoyiannis, MD, ScD, PhD (Hon), FACP, FIDSA, FECMM, FAAM, The University of Texas MD Anderson Cancer Center, Houston, TX
Combination Antifungal Treatment for Mold Infections: Cons
Lindsey Baden, MD, Brigham & Women's Hospital, Boston, MA
Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at
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