Epidemiology of Cryptococcosis and Cryptococcal Meningitis in a Large Retrospective Cohort of Patients After Solid Organ Transplantation

Abstract

Background.Cryptococcosis is the third most common invasive fungal infection in solid organ transplant (SOT) recipients. There are no nationally representative data describing the incidence, risk factors, and outcomes of cryptococcosis after SOT.Methods.We assembled a large cohort of adult SOT recipients using Classification of Diseases, Ninth Revision, Clinical Modification billing data from Healthcare Cost and Utilization Project State Inpatient Databases of Florida (2006–2012), New York (2006–2011), and California (2004–2010). Demographics, comorbidities, death, and cryptococcal infections coded during hospitalization were identified.Results.A total of 42634 adults with SOT were identified during the study period. Cryptococcal disease was identified in 0.37% (n = 158), 44% of which had meningitis (n = 69). Median time to diagnosis of cryptococcosis was 464 days (range, 4–2393). The median time to onset of cryptococcosis was earlier for lung (191 days; range, 7.5–1816), heart (195 days; range, 4–1061), and liver (200 days; range, 4–1581) compared with kidney transplant recipients (616 days; range, 12–2393; P < .001, log rank test). Very early-onset disease (<30 days after transplantation) more frequently occurred in liver and lung transplant recipients. Lung transplant recipients had the highest risk of cryptococcosis (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.21–3.60). Cryptococcosis was associated with death (HR, 2.29; 95% CI, 1.68–3.11), after adjusting for age, type of SOT, and other comorbidities.Conclusions.Cryptococcosis is rare after SOT, but it is associated with significantly increased risk of death. Lung transplant recipients are at highest risk for cryptococcosis among SOTs. Nonkidney transplants have earlier onset of cryptococcosis and higher risk of death compared with kidney transplant recipients.

Outcomes of cryptococcosis in renal transplant recipients in a less‐resourced health care system

“…Over the course of 13 years, 0.8% of renal transplant recipients developed cryptococcosis, and most occurred a long time after transplantation. The incidence of cryptococcosis in renal transplant recipients observed in this study was similar to the low incidence rates reported by other groups (0.3%‐5.5%), but with high mortality . Among these 47 patients, the majority had received AMBd (87.2%) as first‐line therapy.…”

“…Cryptococcosis is specifically recognized as the second most common invasive fungal infection in renal transplant recipients in many countries, including Brazil, with incidence rates ranging from 0.3% to 5.5% and overall mortality rates as high as 20%‐50% have been reported . Amphotericin B formulations are considered the best option for primary therapy and the 2010 IDSA Guidelines recommend lipid formulations of amphotericin B .…”

Fatal fulminant cryptococcemia complicating sarcoidosis: Is it to be expected?

“…The detection of CrAg was greatly improved with the advent of point-of-care diagnostic assays, such as a lateral flow assay for use in serum and other sample types — including whole blood from finger stick samples [10]. However, a “screen and treat” approach based on testing for cryptococcal antigenemia followed by preemptive administration of antifungals is not part of standard practice in non-HIV infected patients [3], while it is a consolidated practice in resource-limiting settings with high incidence of HIV and cryptococcal diseases [14].…”

“…As currently understood, with the advent of effective antiretroviral therapy, the majority of cryptococcosis cases in nations as ours occurs among non-HIV-infected patients [2], especially in those who have a co-existing immunocompromised state [3]. In these patients, lack of suspicion for, and/or delay in diagnosis of cryptococcosis may increase the likelihood of unfavorable outcome [4].…”

Cryptococcal infection in lung transplant recipients: A 5‐year retrospective review at an Australian transplant center

“…Given the exposure of the allograft to the external environment, lung transplant (LTx) recipients might be considered to have the highest risk of cryptococcosis compared with other SOT recipients . Despite this, relatively little is known about cryptococcal infection in this group of patients.…”