The Latest Guidance on Cryptococcosis Treatment in Solid Organ Transplant Recipients

Solid organ transplants (SOT) have grown with medical technology and advanced beyond just kidney and liver. The Organ Procurement and Transplantation Network has reported on not only the variety of solid organ transplants, but also those less conventional, such as uterus, larynx, and face. But beyond the basic supply-and-demand challenges associated with SOT, there are, of course, also the inherent risks to the recipient, namely infection.

In response to the threat of cryptococcosis infections, which is the third most common invasive fungal infection in SOT recipients, the American Society of Transplantation Infectious Diseases Community of Practice has released updated guidelines for the medical management of cryptococcosis in transplant recipients.

Presented in the Journal of Clinical and Translational Research — Clinical Transplantation, the guidelines point out that cryptococcosis infections can be tough to manage because they are often slow-growing, therefore SOT recipients are most likely to experience infection a year or more after transplantation. There have been cases that occur within 3 months, but these are more likely to occur in liver and lung transplant recipients. The 2 most common species causing infections are Cryptococcus neoformans and C gattii. Eight percent of invasive fungal infections in SOT recipients are a result of cryptococcosis, and the incidence in SOT recipients is anywhere between 0.2% and 5%.

Typically found in the environment, this fungus has been known to infect immunocompetent and immunosuppressed individuals. As the investigators note, an infection in a SOT recipient is an indicator of reactivation of quiescent infection (ie, a latent infection that begins to spread). That being said, there have been cases of a primary infection occurring after transplantation, usually a result of inhaling the organism (from bird droppings or soil).

Not surprisingly, immunosuppression is a considerable risk factor for cryptococcosis and those on corticosteroids are at an increased risk. Those who are unlikely enough to experience an infection are often met with non-specific symptoms that can rapidly progress to severe. From pulmonary infections to meningitis, none of the presentations of this fungal infection are particularly pleasant. The investigators note that “overall mortality in SOT patients with cryptococcosis in the current era ranges from 5% to 20%. However, some C gattii infections in SOT recipients have shown mortality up to 70%, despite the use of treatment based on current guidelines.”

In terms of diagnostics, the updated guidelines emphasize the need to determine the site and extent of the disease in order to help provide the most precise and effective antifungal therapy. The investigators recommend that patients who might have a cryptococcosis infection undergo a thorough evaluation including extrapulmonary sites, lumbar puncture, and cultures of the blood, urine, and other necessary tissues. Furthermore, antifungal susceptibility is encouraged to identify those potential species that show potential for fluconazole resistance.

Unfortunately, as the investigators emphasize, there have been no randomized controlled trials of antifungal therapy for SOT recipients who have cryptococcosis infections. Recommendations are pulled from clinical trials involving HIV-infected patients and retrospective SOT recipient data. The investigators note that “lipid amphotericin B plus flucytosine is used as initial treatment of meningitis, disseminated infection, and moderate-to-severe pulmonary infection, followed by fluconazole as consolidation therapy. Fluconazole is effective for mild-to-moderate pulmonary infection. Immunosuppression reduction as part of management may lead to immune reconstitution syndrome that may resemble active disease.” For most experiences, consolidation and pulmonary disease, the duration of treatment is likely to be weeks to months.

Overall, the investigators emphasize the importance of performing a lumbar puncture for diagnosis and evaluation of intracranial pressure, a lipid formation of amphotericin B plus 5-flucytosine as an induction therapy if central nervous system disease is present (or disseminated disease), and fluconazole for consolidation and pulmonary disease, as well as maintenance therapy for CNS. They also note that SOT recipients should not receive routine antifungal prophylaxis against cryptococcosis. Overall, it is important for post-transplantation medical care to be mindful of cryptococcosis infections and the considerable prevalence that exists in SOT recipients. The diagnosis and medical management of these patients is complex, but these new guidelines offer clear and concise strategies to improve patient health.