TREATMENT OF INVASIVE CANDIDIASIS

Early treatment of invasive candidiasis is important for optimal outcomes. For this reason, therapy is often started as early as possible. The treatment may be classified as prophylaxis, empiric therapy, or pre-emptive/targeted therapy.

• Prophylaxis is often started in people who are at very high risk of invasive candidiasis. This includes certain patients with cancer, who have received transplants, who have had low blood counts, and certain patients in the intensive care unit. Providers will look at the number of risk factors (as outlined in the risk factor section) when deciding on whether to provide prophylaxis or not.
• Empiric therapy Sometimes, clinicians will treat empirically for invasive candidiasis, particularly in someone who has a lot of risk factors and has symptoms suggesting an infection, such as a fever. However, and wherever possible, it’s best to have a signal pointing to Candida when initiating therapy. This could be a positive Beta-D-glucan or PCR test. When therapy is guided by such testing, it’s called pre-emptive.
• Targeted therapy is therapy begun when the diagnostic testing has established an invasive candidiasis infection.

Treatment should be guided by the species and antifungal susceptibility testing. This is because certain species are more likely to be resistant at baseline. And therapy should be adjusted based on the findings of antifungal susceptibility. See the Science Sidebar on Candida Resistance.

TREATMENT OPTIONS

In this section, we go over the overall strategies as well as the drugs and other treatments used to manage invasive candidiasis. with a brief discussion of investigational therapies. Generally speaking, the echinocandin drug class is recommended as first-line empirical therapy, with fluconazole as an alternative in certain patients. The species of the organism and the resistance profile are important considerations.

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 Candida 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. For these specific considerations, please speak with your provider about how these factors impact the selection of your therapy.

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

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

Echinocandins 

Echinocandins are medications given by vein that inhibit the synthesis of part of the fungal cell wall. Echinocandins are the preferred drugs for treating invasive candidiasis.

Triazoles

Triazoles are named by their chemical structure. These drugs can interact with a lot of medications, so your provider will need to consider all the medications you are taking when starting azole therapy. Fluconazole, a type of triazole, is an alternative to an echinocandin for invasive candidiasis. The IDSA recommends that it be considered in select patients who are not critically ill and are not likely to have a fluconazole-resistant species. For more on resistant Candida, see the Science Sidebar.

FDA-approved

Other Azoles

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. Amphotericin B type products are generally recommended when the infection is suspected to be caused by Candida that is resistant to azoles or echinocandins, if the patient can’t tolerate an azole, or if there is limited availability.

Antimetabolites

Antimetabolite drugs interfere with the energy production of cells. Flucytosine is an antimetabolite sometimes used as part of combination therapy for invasive candidiasis.

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 invasive candidiasis treatments and search for new and better ones. Clinical trials are essential for learning about the management of invasive candidiasis.

Our most effective antifungal treatments would not be available without the clinical trial process. Unfortunately, many people with invasive candidiasis, 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 was developed, there are some promising therapies in development for invasive candidiasis.

• Fosmanogepix/manogepix is a drug that uses a unique mechanism of action—this IV and oral drug interferes with an enzyme necessary for fungal adherence. Fosmanogepix has shown promising results in clinical trials for invasive candidiasis. It appears to have activity against drug-resistant Candida strains. For a summary of data, please read the following article as well as a more recent review.
• 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 has shown benefit in an open-label study for invasive candidiasis. Ibrexafungerp is being evaluated in some larger invasive candidiasis studies.
• 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 but allows the drug to be taken up into the bloodstream and released in tissue because of calcium differences. At the time of this writing, MAT2203 has special FDA status as an investigational agent for management of invasive candidiasis among other fungal infections. To learn more about MAT2203 for invasive candidiasis, read this article.

Non-pharmacologic management

In order to provide the best possible care for patients with invasive candidiasis, providers need to consider management strategies beyond drugs. These include:

• Eye examination. Candida can affect the eye, causing a condition called Candida endophthalmitis. This condition can lead to vision loss. While there is some controversy over the role of examinations for this condition, a dilated eye exam is recommended by the IDSA.
• Source control. If there is a source of Candida within the body, it is important to control (and if possible) remove that source. A lot of times this can be a central venous catheter. Other times, if there is Candida in the intra-abdominal region, management such as drainage or surgical repair may be required, However, sometimes, the source cannot be controlled. See the SCIENCE SIDEBAR: Chronic Candidiasis on the Living with Invasive Candidiasis page to learn more about special situations where source control is difficult.
• If a person has Candida blood cultures that remain positive, fevers, or disease in the heart valve, an echocardiogram should be considered.
• Infectious-diseases consult. If your healthcare facility provides an infectious diseases consult, you are likely to have better outcomes. It’s worth asking for one!

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.