Cryptococcus neoformansin Organ Transplant Recipients: Impact of Calcineurin‐Inhibitor Agents on Mortality

Abstract

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

Cellulitis Revealing a Cryptococcosis-Related Immune Reconstitution Inflammatory Syndrome in a Renal Allograft Recipient

“…neoformans infections occur with an incidence of 2.8% in renal transplant recipients (3) in a median time of 21 months after transplantation. In this setting, 38% of the patients presented with fungemia in a study (3) and 21% with skin, soft tissue or osteoarticular infection as in our patient in another study (4). A 14% mortality rate has been observed at 3 months reaching up to 33% in case of fungemia (3).…”

Cavitary lung lesion 6 years after renal transplantation

“…Presence of chronic liver disease and use of steroids, T cell depleting antibodies and Alemtuzumab are specifically associated with increased risk of Cryptococcosis. Calcineurin inhibitor based regimens are believed to be protective, being associated more commonly with Cryptococcosis limited to lungs with less likelihood of dissemination [5,6] . Our patient is HBsAg positive.…”

“…If Flucytosine is not available, which was the case initially in our patient, Amphotericin should be given for a minimum of 4-6 wk [5] . Cryptococcal infection has an overall mortality of 14% in solid organ transplant recipients [6] . Early diagnosis and initiation of treatment is the key to survival.…”

Fungal Infections in Transplant and Oncology Patients

“…Current IDSA guidelines recommend amphotericin B plus flucytosine for 2 weeks, followed by fluconazole orally at 400-800 mg for up to 10 weeks, followed by a decreased dose of fluconazole (200 mg) for 6-12 months [115] for CNS or other severe disease. There is some data to suggest that in SOT recipients with isolated pulmonary cryptococcosis, prolonged treatment with oral fluconazole is sufficient and induction therapy with amphotericin B may not be necessary [116].…”