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Background: Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed., Methods: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis., Results: Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001)., Conclusions: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.

Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known., Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis., Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline (P = .94 ). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (P = .034), renal failure at baseline (P = .016), and fungemia (P = .003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P = .007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P = .349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P = .047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P = .004 ) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; P = .008)., Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

Abstract: Background: The role of Th1 and Th2 mediated cytokine responses in the pathogenesis of Cryptococcus neoformans infection in organ transplant recipients has not been defined. Methods: We assessed cytokine levels in the sera and CSF collected prospectively at the time of diagnosis of infection in 25 transplant recipients with cryptococcosis. Serum levels were compared with those in healthy individuals and transplant recipients without cryptococcosis. IFN-γ or IL-12 (Th1)/IL-10 (Th2) ratio <1.0 was considered a dominant Th2 response. Results: Cases had lower ratios of IFN-γ/IL-10 (p =0.03) and IL-12/IL-10 (p =0.03) compared to healthy individuals. Cytokine responses, however, did not differ significantly for cases vs. transplant controls. Cases with fungemia compared to those without fungemia tended to have higher serum IL-10 levels (p =0.07) and lower IL-12/IL-10 ratios (p =0.06). CSF ratios of IFN-γ/IL-10 (p =0.04) and IL-12/IL-10 (p =0.04) were lower in cases with cryptococcal meningitis compared to those without meningitis; 80% (8/10) of the cases with cryptococcal meningitis vs. 0% (4/4) of those without meningitis had CSF IFN-γ/IL-10 ratio of <1.0 (p =0.015). The levels of IL-10 (p =0.04) and IFN-γ (p =0.04) in the CSF in cases with cryptococcal meningitis were significantly higher than those in their serum, respectively. Conclusions: High expression of Th2 phenotype in cryptococcal meningitis and in fungemia suggests that Th dysregulation may contribute to the pathogenesis of cryptococcosis in organ transplant recipients. [Copyright &y& Elsevier]