Central nervous system candidiasis beyond neonates: Lessons from a nationwide study.

Though candidiasis is the most frequent invasive fungal infection, Candida spp. central nervous system (CNS) infections are rare but severe. To further describe clinico-patho-radiological presentations of this entity, we report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included. Seventeen patients (70%) had CNS localization secondary to disseminated candidiasis (10 with hematologic malignancies [HM]; the seven other patients had infective endocarditis [IE]). Among patients with HM, seven previously had lumbar puncture for intrathecal chemotherapy, the three others had IE. Among patients with disseminated infection, magnetic resonance imaging (MRI) evidenced meningitis (17%), micro-abscesses (58%), or vascular complications (67%). Seven patients (30%) had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use, diabetes mellitus, or no identified predisposing condition (n = 1 each). All evaluated patients with isolated CNS involvement had meningitis on cerebrospinal fluid (CSF) and intracranial hypertension. For the latter patients, MRI evidenced meningitis (71%) or abscesses (57%). Among all patients, cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. CSF ßDGlucan or mannan Ag were positive in respectively 86% and 80% of cases. Mortality attributed to CNS candidiasis was 42%: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection. CNS candidiasis are isolated or occur during disseminated infection in patients with HM and lumbar puncture for intrathecal chemotherapy or during IE. Clinical, radiological finding and outcome highly vary according to CNS localized versus disseminated candidiasis. LAY SUMMARY: Candida is a yeast and is the most common cause of fungal infections worldwide. Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged ≥ 28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n = 2), CARD9 deficiency (n = 2), intravenous drug use (n = 1), diabetes mellitus (n = 1), or no identified risk factor (n = 1).During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.

Paracoccidioidomycosis in the Central Nervous System

Paracoccidioidomycosis is a systemicmycosis caused by the Paracoccidioides brasiliensis fungus, which is endemic in Latin America. Brazil is the country with the highest number of cases. The affection of the central nervous system (CNS), a potentially fatal condition, occurs in 12% of the cases. The following forms of presentation are identified:meningeal, which is unusual;meningoencephalitic; and pseudotumoral, the latter two being more frequent. Imaging tests are essential for the diagnosis, but the histological identification of the fungus is required for confirmation of the pathology. The clinical picture depends on the neuraxial location.We present a case of amale rural worker, with expansive lesions in the CNS compatible with paracoccidioidomycosis.

Pre-operative Voriconazole in patients undergoing surgery for Central Nervous System fungal infections: Special Report.

Fungal infections of the central nervous system (CNS) are uncommon. Despite several advancements in diagnosis and treatment of these infections, the mortality rates remain high. The current retrospective study was planned to define the demographic and clinical features of patients with CNS fungal infections. Conducted at Aga Khan University Hospital, Karachi, and comprising CNS fungal infections operated between January 2000 and December 2015. The study analysed whether a short course of pre-operative anti-fungal therapy may improve outcomes in these patients. There were 47 cases confirmed on histopathology and/or microbiology. Outcome measures used were Glasgow coma score (GCS), Glasgow outcome score (GOS) and Karnofsky performance score (KPS). The overall 30-day mortality was 20(42.5%). Fungal infections of the CNS can occur in both immune-compromised and immune-competent patients. Early diagnosis, radical surgery, pre-operative anti-fungal therapy for at least 2 weeks, pre- and postoperative Voriconazole therapy results in more favourable outcomes.

A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?

BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper. SEARCH STRATEGY: An extensive Medline literature search was performed for case reports published between 1994 and 2015. RESULTS: In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%. CONCLUSIONS: Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.

Pharmacokinetics-pharmacodynamics of antifungal agents in the central nervous system.

INTRODUCTION: Mortality from invasive fungal disease involving the central nervous system (CNS) is excessive. Achieving therapeutic drug concentrations at the site of infection within the CNS is always difficult and its evaluation is complex due to anatomical barriers and variable pathophysiological lesions. Areas covered: This review provides an updated summary of the CNS PK of antifungal therapies. It considers factors that influence the success of antifungal regimens for CNS infection as well as preclinical and clinical data that quantify antifungal pharmacokinetics (PK) in the CNS. Furthermore, it presents state-of-the-art technologies to enhance the clinical use of existing antifungal drugs, and introduces novel antifungal drugs in development. Expert opinion: The antifungal drugs currently available are either suboptimal, or are being used suboptimally, for CNS disease. Therapeutic drug monitoring is mandatory to enhance their effectiveness. Novel drugs in development may offer more efficacious options. In all cases, contemporary technologies to assess CNS PK offer the opportunity to enhance our understanding and use of antifungal drugs for CNS fungal disease.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Autopsy and biopsy study of paracoccidioidomycosis and neuroparacoccidioidomycosis with and without HIV co-infection.

Paracoccidioidomycosis (PCM) is a systemic mycosis prevalent among immunocompetent patients in Latin America. This study aimed to describe the frequency, demographics and clinical characteristics of central nervous system PCM (NPCM) and PCM in an endemic region, and the impact of human immunosuppression virus (HIV) co-infection. This was a retrospective study of autopsy and biopsy reports from the Medical Pathology Section of the Hospital de Clinicas, UFPR, Curitiba, Southern Brazil, between 1951 and 2014. PCM was present in 0.1% of 378,323 cases examined, with 5.7% being NPCM. Infection was prevalent in working-age men, agricultural workers and rural residents. Numbers of HIV autopsy cases increased over time, while those of PCM cases decreased. Prevalence of co-infection of HIV/PCM and HIV/NPCM was 1.6%, and 0.4%, respectively. Adrenals were affected more frequently in the NPCM group compared with the PCM group. Mortality was higher on NPCM group. The clinical course of PCM in HIV patients resembles an acute/sub-acute infection. Association of NPCM and HIV is rare, while diagnosis of NPCM is difficult, it should be considered a differential diagnosis in HIV patients who live in, or have visited, endemic areas and present with neurological symptoms.

Invasive mold infections of the central nervous system in patients with hematologic cancer or stem cell transplantation (2000-2016): Uncommon, with improved survival but still deadly often.

BACKGROUND: Historically considered to have very poor outcome, there is paucity of recent data regarding invasive mold infections (IMIs) of the central nervous system (CNS) in patients with hematologic cancer (HC) or stem cell transplantation (SCT). METHODS: We reviewed the records of HC patients and/or SCT recipients who were diagnosed with CNS IMIs (EORTC/MSG criteria) at MD Anderson Cancer Center (1/1/2000-6/31/2016). Risk factors for survival at day (d) 42 post diagnosis were assessed. RESULTS: We identified 40 such patients (16 with proven infection). The incidence density was 3.8 cases/100000 patient days and mortality remained stable throughout the study period. Most patients had active HC and neutropenia at diagnosis (95% and 53% respectively). Of the 25 patients with a microbiological diagnosis, Aspergillus spp and Mucorales accounted for 85% of cases. CNS IMIs were deemed to be secondary to hematogenous spread in 31 (77%), mostly (90%) fungal pneumonia. CNS lesions typically presented as solitary ring-enhancing abscesses in MRI (26; 65%). Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%); Mortality 42d was 48%. In univariate analysis, lack of surgical drainage (p = 0.01), absence of giant cells (p = 0.01) and granulomas (p = 0.03) were associated with increased 42d mortality. In multivariate analysis, co-infection was associated with increased (p = 0.005), while steroid tapering was associated with decreased mortality (p = 0.01). CONCLUSIONS: Although less lethal, improved outcome in these uncommon infections was related only to immune response in histopathology, steroid tapering and possibly surgical drainage. In a contemporary 16-year cohort of 40 patients with hematologic cancer and mold infections of Central Nervous System, 42-day mortality was 48%. Improved survival was related to immune response in histopathology, absence of co-infections, corticosteroid tapering and possibly surgical drainage.

An updated comprehensive systematic review of Cladophialophora bantiana and analysis of epidemiology, clinical characteristics, and outcome of cerebral cases.

Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.

Epidemiology and outcomes of invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients in the era of antifungal prophylaxis: a single-centre study with focus on emerging pathogens.

With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp., Cladosporium sp., Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g(-1)  dl(-1) increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

Intracranial Fungal Granulomas: A Single Institutional Clinicopathologic Study of 66 Patients and Review of the Literature.

INTRODUCTION: Fungal granulomas of the central nervous system are rare and have a high rate of mortality and morbidity, irrespective of treatment. The authors report their experience of managing 66 patients during 15 years and discuss the clinical, radiological, surgical, and pathologic findings. This series is among the largest reported. MATERIAL AND METHODS: A retrospective analysis was performed on patients with intracranial fungal granulomas (ICFGs), treated in the authors' institution, between January 1997 and May 2011. Only mass-forming histopathologically proven ICFGs were included in this study. RESULTS: The age of the patients ranged from 7 years to 67 years (mean = 32.3 years), and most patients were in the third and fourth decades of life. The study population comprised 47 male and 19 female patients. The most common symptom was headache (41 patients), followed by vomiting (16 patients) and blurring of vision (16 patients). Only 3 patients presented with fever. The duration of symptoms was less than 6 months in all cases and less than 3 months in 39 cases. Anterior cranial fossa and frontal lobe was involved in 35 cases (54.5%), followed by middle cranial fossa in 20 cases (30.3%). Three cases had granulomas in the cerebellopontine angle. Three cases had multicompartmental involvement, and 4 had multilobar involvement. Nine patients had predisposing factors for fungal infection Based on clinical and imaging data, preoperative diagnosis of a possible fungal lesion was made in 44 (some had only computed tomography imaging) patients. All the patients were treated surgically, followed by antifungal treatment with amphotericin-B and/fluconazole/itraconazole for a period of 6 weeks. Eight patients had symptomatic recurrence of lesions 3-12 weeks after treatment and underwent reoperation. Six patients were lost to follow-up. Nine patients died in the postoperative period (within 30 days postoperatively). Fifteen patients died during follow-up because of recurrent lesions, repeat surgery, renal failure, and unrelated causes. Overall mortality was 24 (36.3%). Poor neurologic status before surgery, emergency craniotomy, severe brain edema with mass effect, and opening of ventricles during surgery were associated with poor outcome. Aspergillus species were the causative organism in an overwhelming majority of patients (n = 52) followed by Mucor in 7 cases, Cladosporium in 3 cases, eumycetoma in 2 cases, and maduramycosis and blastomycosis in 1 case each. CONCLUSION: ICFGs have high rates of morbidity and mortality. Early diagnosis, radical surgery, and antifungal treatment for 6 weeks may improve outcome. Poor neurologic status of patients at the time of presentation, immunocompromised state, contamination of ventricular cerebrospinal during surgery, and renal failure (attributable to amphotericin-B) are associated with poor outcome.

Looks like a stroke, acts like a stroke, but it's more than a stroke: a case of cerebral mucormycosis.

Mucormycosis is a fungus that exhibits angiocentric growth and can cause a thrombotic arteritis. Infection with this organism is uncommon and cerebral involvement is most often secondary to direct invasion through the paranasal sinuses. Here, we present a case of mucormycosis with cerebral involvement without sinus disease, which resulted in ischemic stroke with rapid progression resulting in death.

Late-onset sepsis in very low birth weight infants: a Brazilian Neonatal Research Network Study.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants. AIM: To determine the incidence, risk factors and etiology of LOS. METHODS: LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days. RESULTS: Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation. CONCLUSION: LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.

Rhinocladiella mackenziei as an emerging cause of cerebral phaeohyphomycosis in Pakistan: a case series.

Six cases of Rhinocladiella mackenziei cerebral phaeohyphomycosis are being reported for the first time in Pakistan. Identification was confirmed by DNA sequencing (isolates and fixed tissue). Diabetes, head trauma, immunosuppressive treatment, and postpartum state were present in 4 cases. Two survivals and 3 fatalities occurred, with 1 patient lost to follow-up.

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases.

AIM: To investigate mortality risk factors in patients with zygomycosis. PATIENTS AND METHODS: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. RESULTS: We identified twenty-five patients with proven zygomycosis. The primary site of infection was rhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008). CONCLUSION: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment.

Outcomes of central nervous system cryptococcosis vary with host immune function: results from a multi-center, prospective study.

BACKGROUND: Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients. METHODS: We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n = 54), HIV-negative immunosuppressed patients (n = 21), and non-immunosuppressed patients (n = 11). RESULTS: Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p < 0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p = 0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p = 0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p = 0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p = 0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p = 0.05). The mortality rate was greatest for non-immunosuppressed patients (p = 0.04). CONCLUSION: CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.

Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era.

BACKGROUND: Central nervous system (CNS) involvement with Blastomyces dermatitidis is an uncommon and potentially fatal complication of blastomycosis. METHODS: We retrospectively reviewed 22 patients with CNS blastomycosis at our institutions from 1990 through 2008 (13 proven, 5 probable, and 4 possible cases). RESULTS: Magnetic resonance imaging was used in most patients, alone or in addition to computed tomography. CNS blastomycosis manifested as epidural abscess (1 of 22), meningitis (7 of 22), intracranial mass lesions (10 of 22), and concomitant intracranial mass lesions and meningitis (4 of 22). All patients received amphotericin B deoxycholate or a lipid formulation of amphotericin B as part of their treatment regimens. Most patients received amphotericin B followed by a prolonged course of oral azole therapy (voriconazole, fluconazole, or itraconazole). Four (18%) of 22 patients died during follow-up. CONCLUSIONS: On the basis of these data, we recommend initial treatment with a lipid formulation of amphotericin B followed by a prolonged course of oral azole therapy, preferably voriconazole.

Cutaneous cryptococcosis in solid organ transplant recipients.

Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system (88.9%, 16/18), lung (33.3%, 6/18), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure (75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis.

Central nervous system involvement in cryptococcal infection in individuals after solid organ transplantation or with AIDS.

BACKGROUND: Cryptococcus neoformans is an important pathogen of immunocompromised hosts. Manifestations of cryptococcal infection have not been compared between populations based on the nature of the underlying immune deficiencies. METHODS: The Prospective Antifungal Therapy Alliance (PATH) is a registry that collects clinical data from patients with invasive fungal infections from medical centers in North America. Univariate analyses and group comparisons were conducted from the PATH registry for cases of infection due to Cryptococcus species occurring between March 2004 and April 2008. RESULTS: A total 235 cases of proven infection due to Cryptococcus species were documented, all of which were due to C. neoformans (52 in solid organ transplant [SOT] recipients, 107 in patients infected with the human immunodeficiency virus [HIV], and 76 with neither HIV nor organ transplantation). A total of 140 cases manifested as meningitis (25 in SOT recipients, 88 in HIV-positive patients, and 27 in those with neither risk factor). Of individuals with cryptococcal infection, 44.2% of SOT recipients had central nervous system (CNS) disease, while 84.1% of those with HIV infection presented with CNS involvement (P=0.0265). SOT recipients receiving calcineurin inhibitors (CNIs) were less likely to have CNS involvement in cryptococcal infection (40.1% versus 66.7%). Overall, 12-week mortality for patients with cryptococcal infection in the PATH Alliance registry was 22.6% (21.2% for SOT, 15.9% for HIV-infected patients, and 32.9% for patients with risk factors other than HIV infection or organ transplantation). CONCLUSIONS: In a prospectively assembled cohort of individuals with proven infection due to C. neoformans, CNS involvement was more common in individuals with HIV infection than in SOT recipients. The role of CNIs in the reduction of risk for CNS cryptococcosis remains to be defined. Overall survival of patients with cryptococcal infection in immunocompromised hosts has improved over time. Observed differences in the context of various host immune deficits provide a basis for further investigation of cryptococcosis and other opportunistic infections.