TREATMENT OF ASPERGILLOSIS

Allergic Forms

The management of allergic forms of aspergillosis may involve several strategies, depending on the particular type of allergic aspergillosis and the stage of the disease. Below are some of the treatments that may be used.

Medications 

Steroids (corticosteroids)

Steroids are used to reduce inflammation and manage symptoms. They are used to reduce inflammation in various diseases.

Steroids are commonly used medications, but they have to be used in a very specific way. Here are some common tips for getting the best results from steroids:

• Take your medication exactly as prescribed.
• Your provider may encourage you to take the medicine in the morning—sometimes steroids can cause you to become excessively energetic, so it’s best not to take them at night. If you take the medicine at night, you may be too wound up to sleep.
• They can cause indigestion—your provider may want to provide antacid therapy. Take the steroid with food.
• If you are having mood changes—becoming angry, reactive, or hyper—let your provider know. They may adjust the dose.
• Anticipate that your provider will wean you from steroids over a period of time—you should not stop cold turkey (suddenly and completely).
• If you have diabetes, care must be taken in giving you steroids, since they can elevate your blood sugar.

Antifungal Medications

Sometimes antifungals are used along with corticosteroids or instead of corticosteroids for allergic forms of aspergillosis. Your provider will make the best decision for you. For allergic aspergillosis, itraconazole and voriconazole are the antifungal agents used most often. A more detailed discussion of antifungals is included in the Treatment of Invasive Aspergillosis section below.

Other Medications

Nasal steroids: Nasal spray steroids can be used to reduce inflammation in patients with allergic fungal rhinosinusitis.

Bronchodilators: These are medications to help open the airways and improve breathing. They are used in some of the allergic forms of aspergillosis.

Invasive Aspergillosis 

Invasive aspergillosis is a serious condition, so a lot of effort is made to try to prevent it or treat it aggressively. Some general principles apply to management of invasive aspergillosis. These include:

TREATMENT OPTIONS

In this section, we go over the drugs and other treatments used to manage aspergillosis, with a brief discussion of investigational therapies as well. Prior to the introduction of the triazole antifungals, amphotericin was the recommended therapy for invasive aspergillosis. You will notice that it is the drug that was used as the comparator in many of the older studies.

We have arranged the drugs in alphabetical order by class of drug because sometimes your doctor will recommend switching the antifungal drug class or combining classes of drugs when the first treatment is not effective. While polyenes were the first class of agents used for aspergillosis, triazoles were found effective and safe and are now generally recommended first. But polyenes and even drugs belonging to the class echinocandins are also options for patients who can’t take triazoles or aren’t responding to them.

It’s important to note that we provide generalizations about these therapies. Your provider will work with you to determine the best course of therapy for you. Your provider will consider the type of Aspergillus you have, your medical history, and other factors such as kidney function, other medicines you are taking, and whether you are pregnant or breastfeeding when selecting your therapy.

While all of the drugs listed below are FDA-approved, some are not specifically approved to treat Aspergillus infection but are discussed in the Infectious Diseases Society of America Aspergillus Guidelines.

Finally, all of the data discussed are related to management of invasive aspergillosis in adults. Information for pediatric patients is coming in a later module.

Triazoles 

Triazoles are the most commonly used drugs for invasive aspergillosis. Many of these medicines can be provided both by mouth and vein. They are named by their chemical structure. Azoles can interact with a lot of medications, so your provider will need to consider all the medications you are taking when starting azole therapy. The FDA-approved azoles are listed first.

FDA-approved Triazole Therapies

Polyenes 

These drugs are derivations of amphotericin B and are named for their chemical structure. At this time, these drugs must be given by vein, but a version that can be delivered by mouth is being studied (See Clinical Trials).

Echinocandins

Echinocandins are medications given by vein that inhibit the synthesis of part of the fungal cell wall. These drugs are typically used as alternatives to azoles or as part of a combination approach.

Clinical Trials and Investigational Agents

Clinical trials are research studies that test how well new treatment approaches work. They have an important place in your care as researchers strive to improve current aspergillosis treatments and search for new and better ones. Clinical trials are essential for learning about the management of invasive aspergillosis.

Our most effective antifungal treatments would not be available without the clinical trial process. Unfortunately, many people with aspergillosis, or their loved ones, are unaware of the option for a clinical trial or are unsure about the value of participating.

Your goal is to find the best treatment available whenever you make a treatment decision. While there may be a good standard of care for you or your loved one—care that experts believe is appropriate for your specific diagnosis and treatment history—sometimes the current standard of care is not as effective as you and your healthcare team would like. Other times, the standard of care works for a time but then stops working. In still other instances, there is no standard of care for your situation. Participation in a clinical trial may be the best option for you.

The best time to search for clinical trials is every time you are faced with a treatment decision.

At the time this website has been developed, these are some promising therapies in development for invasive aspergillosis:

• Olorofim is an oral drug that belongs to a novel class of drugs called orotomides. This drug has good activity against a variety of Aspergillus spp. It can penetrate the lung, liver, kidney and brain and has low potential for drug-drug interactions. In the FORMULA-OLS study, olorofim had positive outcomes for patients with invasive aspergillosis and limited or no treatment options. To learn more about the results of this preliminary study, look here
• Fosmanogepix is another drug using a unique mechanism of action—this IV and oral drug interferes with an enzyme necessary for fungal adherence. It also has broad activity against a number of Aspergillus species, alone and in combination with liposomal amphotericin B. A small study that was stopped in 2022 showed promising results in invasive mold infections. A larger study is launching at the time of this writing
• Ibrexafungerp belongs to a new class called the triterpenoid class, which has some similarities to echinocandins but with lower rates of cross-resistance. This drug interferes with the building of the fungal cell wall. Already FDA-approved for vulvovaginal candidiasis treatment and prevention, ibrexafungerp showed favorable responses in a study conducted in patients with refractory fungal diseases, including those with invasive aspergillosis. It’s also being studied in combination with voriconazole specifically for patients with invasive aspergillosis
• Opelconazole is a triazole drug specifically designed for inhalation therapy. Inhalation therapy for invasive pulmonary aspergillosis is appealing because it gets the drug to the areas needed with fewer side effects and drug-drug interactions. Opelconazole is active against a number of Aspergillus species. It has been studied as prophylaxis against aspergillosis and is being studied in combination with other systemic drugs in refractory invasive aspergillosis
• MAT2203 is an oral and non-toxic encochleated form of amphotericin B (CamB). Encochleation means that the drug is wrapped up in fat-based crystals and calcium that protect the drug from getting broken down within the GI tract. Encochleation also allows the drug to be taken up into the bloodstream and released in tissue because of calcium differences. At the time of this writing, a study is planned with MAT2203 after IV amphotericin B therapy for patients who can’t tolerate azoles (the ORALTO trial).

Surgery

Sometimes surgery is needed to manage various forms of invasive aspergillosis. These include:

• Invasive aspergillosis in the sinuses or the eye
• Invasive aspergillosis in the lungs not responding to treatment
• Aspergilloma (fungus ball) (if possible) when the patient is symptomatic, particularly if coughing up blood
• Endocarditis (in combination with antifungal therapy) with replacement of infected valves if necessary
• Osteomyelitis
• Septic arthritis
• Skin lesions when there are burns or a lot of soft tissue wounds.

Supportive Care: This includes measures to support the body’s functions, such as oxygen therapy, IV fluids, and treatment of any underlying conditions. In some cases, growth factors and other immune stimulation drugs can be considered to support neutrophil levels and fight the fungus.