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PubMed1995

Amphotericin B as primary therapy for cryptococcosis in patients with AIDS: reliability of relatively high doses administered over a relatively short period.

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.

AIDS-Related Opportunistic Infections↗
PubMed1999

Fluconazole, with or without dexamethasone for experimental cryptococcosis: impact of treatment timing.

The time of initiation of fluconazole treatment with or without dexamethasone, and the impact on mycological outcome and drug pharmacokinetics were assessed in a murine model of disseminated cryptococcosis. Non-infected mice and mice with disseminated cryptococcosis were given saline, dexamethasone, or fluconazole +/- dexamethasone, 1 or 8 days after infection. Cfus were counted in tissues, and fluconazole concentrations were determined in plasma and tissues by HPLC and a bioassay. Despite fluconazole tissue and plasma concentrations which were above the minimal inhibitory concentration, the numbers of cfus in brain and lung tissues were reduced after early (P = 0.002 and 0.04, respectively), but not after late fluconazole treatment. The administration of dexamethasone did not have a deleterious effect on the number of cfus, fluconazole pharmacokinetics or antifungal activity. In conclusion, the size of the fungal burden influences the effective level of fluconazole activity in lung and brain. These results strongly suggest that potential antifungal agents should be studied following both early and late administration in experimental cryptococcosis.

Animals↗
PubMed1993

Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

MRI of choroidal plexus involvement in intracranial cryptococcosis.

OBJECTIVE: The sensitivity of medical imaging in the diagnosis of intracranial cryptococcosis is poor. MRI can provide additional information in establishing this diagnosis. MATERIALS AND METHODS: We present two cases of CNS cryptococcosis (HIV negative) studied by MRI and discuss the involvement of the ventricles and the choroid plexuses. RESULTS: The choroid plexuses are unusually enlarged and they enhance intensely. Intraventricular loculations were also noted including entrapment of CSF in the temporal horns. CONCLUSION: The constellation of these findings is highly suggestive of cryptococcosis.

Adult↗
PubMedDate not supplied

Dentate nuclei involvement in AIDS patients with CNS cryptococcosis: imaging findings with pathologic correlation.

PURPOSE: Our goal was to describe the involvement of the dentate nuclei in AIDS patients with CNS cryptococcosis since this finding has not been emphasized in previous radiological literature. METHOD: Plain and contrast-enhanced CT of the brain (10 and 10), MR studies (1 premortem and 1 postmortem), and autopsy findings in 11 AIDS patients with CNS cryptococcosis were reviewed. The imaging studies and pathological specimens were analyzed for signs of meningitis, presence of dilated Virchow-Robin spaces, gelatinous pseudocysts, cryptococcoma, ventriculomegaly, choroid plexus, and ependymal lesions. RESULTS: Five of 11 patients were found at autopsy to have macroscopically visible "cystic" lesions in the dentate nuclei that were not detected on CT (10 patients), but were seen on premortem MR (1 patient). Macroscopic supratentorial (basal ganglia, thalamic, midbrain) lesions were detected by CT in 5 of 11 patients and by MR in 2 of 2 patients. Enhancement of the leptomeninges was seen in only 1 patient by CT despite pathological evidence of cryptococcal meningitis in all 11 patients. Dilated Virchow-Robin spaces were seen in all 11 pathologic specimens and in the 2 MR studies but not on CT. Communicating hydrocephalus was detected by CT in two patients. CONCLUSION: CT scans of the brain underestimate infratentorial parenchymal cryptococcal disease. MR is a more sensitive procedure to evaluate cerebellar and brainstem cryptococcosis, including the dentate nuclei, which in our autopsy series was not an uncommon site to be infected with cryptococcal gelatinous pseudocysts.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Pulmonary cryptococcosis: CT and pathologic findings.

PURPOSE: The purpose of this work was to describe the CT and pathologic findings of pulmonary cryptococcosis. METHOD: CT scans of 11 patients (7 immunocompromised, 4 immunocompetent) with proven pulmonary cryptococcosis were analyzed for number, morphologic characteristics, and distribution of parenchymal abnormalities as well for presence of lymphadenopathy and pleural effusion. Pathology of lung specimens obtained by open biopsy or resection (n = 5) and transbronchial biopsy (n = 1) was reviewed by one dedicated pulmonary pathologist. RESULTS: Pulmonary nodules, either solitary or multiple, were the most common CT finding, present in 10 of 11 patients (91%); associated findings included masses (n = 4), CT halo sign (n = 3), and consolidation (n = 2). On histologic examination, focal areas of ground-glass attenuation surrounding or adjacent to nodules were found to represent airspace collections of macrophages and proteinaceous fluid. CONCLUSION: Pulmonary cryptococcosis should be considered in the differential diagnosis of solitary or multiple pulmonary nodules (with or without associated CT halo sign), particularly in immunocompromised patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis.

A case of hepatobiliary dysfunction as the initial manifestation of disseminated cryptococcosis is described. The patient was admitted with symptoms of hepatitis with cholestatic jaundice. Antibody tests for hepatitis B and C and human immunodeficiency virus were negative. The patient continued to deteriorate clinically. Eventually, the patient succumbed to hepatic failure. Autopsy disclosed systemic cryptococcosis that caused extensive necrosis of the liver. In review of the literature, only nine cases of cryptococcal infection presenting as hepatitis, cholangitis, and cholecystitis as initial manifestation were reported. Four of these patients had been subjected to exploratory laparotomy for clinical suspicion of acute abdomen. One patient developed cirrhosis as a result of cryptococcal hepatitis. Two patients succumbed to hepatic failure. Cryptococcosis is known to occur commonly in immunocompromised patients, yet only two reported cases presenting as hepatitis were associated with immunocompromised status.

Aged↗
PubMed1999

Rapid respiratory deterioration and sudden death due to disseminated cryptococcosis in a patient with the acquired immunodeficiency syndrome.

We report the case of a patient with the acquired immunodeficiency syndrome (AIDS) whose death occurred within 30 hours of hospitalization due to disseminated cryptococcosis, manifested by dizziness, cough, and shortness of breath. The clinical picture was consistent with pneumocystis pneumonia, and antibiotic therapy with corticosteroids was initiated. Despite initial improvement, the patient's condition quickly worsened, resulting in cardiorespiratory arrest and death. Autopsy revealed cryptococci in several organs. Sudden, rapid deterioration and death are rare consequences of disseminated cryptococcosis, and steroids may worsen the course of the disease. On the basis of this case and review of similar cases in the literature, we recommend early consideration of disseminated cryptococcosis in AIDS patients with pneumonia. Early diagnosis and appropriate therapy are essential to reduce morbidity and mortality.

AIDS-Related Opportunistic Infections↗
PubMed2004

Primary cutaneous cryptococcosis in a lung transplant recipient.

Cryptococcal skin lesions are found in 10 to 15% of patients with disseminated cryptococcosis. Primary skin inoculation by Cryptococcus neoformans is rare but has been reported. We report the first known case of primary cutaneous cryptococcosis in a lung transplant recipient. Our patient, a 57-year-old man, underwent left single-lung transplantation and presented with a nonhealing ulcer 50 months later. Skin histopathology and culture confirmed C. neoformans. Serum and cerebrospinal fluid cryptococcal antigen tests were negative. The lesion healed after treatment with fluconazole. To date, disseminated disease is not evident. Primary cutaneous cryptococcosis has been reported in kidney and liver recipients but not in lung transplantation recipients. Nonhealing ulcers in immunocompromised patients mandate aggressive diagnostic procedures. Differential diagnosis of these cutaneous lesions should consider fungi, including C. neoformans.

Cryptococcosis↗
PubMed2006

Population-based surveillance for cryptococcosis in an antiretroviral-naive South African province with a high HIV seroprevalence.

OBJECTIVES: To measure the burden of disease and describe the epidemiology of cryptococcosis in Gauteng Province, South Africa. DESIGN AND METHODS: The study was an active, prospective, laboratory-based, population-based surveillance. An incident case of cryptococcosis was defined as the first isolation by culture of any Cryptococcus species from any clinical specimen, a positive India ink cryptococcal latex agglutination test or a positive histopathology specimen from a Gauteng resident. Cases were identified prospectively at all laboratories in Gauteng. Case report forms were completed using medical record review and patient interview where possible. RESULTS: Between 1 March 2002 and 29 February 2004, 2753 incident cases were identified. The overall incidence rate was 15.6/100 000. Among HIV-infected persons, the rate was 95/100 000, and among persons living with AIDS 14/1000. Males and children under 15 years accounted for 49 and 0.9% of cases, respectively. The median age was 34 years (range, 1 month-74 years). Almost all cases (97%) presented with meningitis. Antifungal therapy was given to 2460 (89%) cases of which 72% received fluconazole only. In-hospital mortality was 27% (749 cases). Recurrences occurred in 263 (9.5%) incident cases. Factors associated with death included altered mental status, coma or wasting; factors associated with survival included employment in the mining industry, visual changes or headache on presentation. CONCLUSIONS: This study demonstrates the high disease burden due to cryptococcosis in an antiretroviral-naive South African population and emphasizes the need to improve early recognition, diagnosis and treatment of the condition.

AIDS-Related Opportunistic Infections↗
PubMed1996

Disseminated cryptococcosis with cutaneous lesions.

A case of disseminated cryptococcosis in an HIV-negative patient presenting with cutaneous lesions is described for the first time in Egypt. The patient, a 16-year-old male, presented with cough, expectoration, loss of weight, and cutaneous lesions, mainly on the face and trunk. The lesions consisted of vegetating crusted plaques discharging purulent to sanguinous fluid and flattened, shiny, erythematous to brownish plaques. Anorexia, headache and personality changes soon followed. Histopathological examination of lesions was highly suggestive of a deep mycosis, particularly cryptococcosis. The fulminant disease advanced with central nervous system involvement. The progression was not arrested when systemic antifungal therapy was administered late in the disease course. Pathological examination of lungs, liver, pancreas and spleen revealed disseminated infection with no evidence of other underlying pathology. Disseminated cryptococcosis is a morbid infection, rare in an area where heightened awareness and raised index of suspicion will surely allow earlier diagnosis, management and better prognosis.

Adolescent↗
PubMed1992

Cutaneous cryptococcosis: recurrence following oral fluconazole treatment.

A case of recurrent cutaneous cryptococcosis in an immunocompromised patient is described. The patient presented with a non-healing cutaneous ulcer due to infection with Cryptococcus neoformans. Extensive investigation failed to reveal any evidence of associated systemic cryptococcosis. Treatment with oral fluconazole resulted in complete resolution of the ulcer but after several months a second cutaneous cryptococcal lesion appeared, strongly suggesting dissemination from an underlying systemic focus. This case illustrates the hazards associated with making a diagnosis of isolated cutaneous cryptococcosis and the necessity for prolonged follow-up of patients who present in this way.

Administration, Oral↗
PubMed1990

Cryptococcosis in a renal unit.

Cryptococcosis is a known opportunistic infection in immunosuppressed hosts. We report our experience of all cases presenting to our Department between December 1975 and September 1988. Eight post-renal transplant patients and three systemic lupus erythematosus (SLE) patients were affected. All were receiving treatment with steroids, in association with either azathioprine or cyclosporin. The diagnosis of cryptococcal meningitis was initially based on a positive cerebrospinal fluid (CSF) cryptococcal antigen, by latex agglutination test, and subsequently confirmed by cultures. Common clinical presentations, in descending order of frequency, included headaches, fever, mental confusion, epilepsy and papilloedema. Meningism was not a prominent feature. CT brain scans were obtained in eight patients and one showed a focal lesion and one showed cerebral atrophy. Four patients also had an abnormal chest X-ray (CXR) and one had disseminated cryptococcosis. Amphotericin and 5-fluorocytosine were the mainstay of therapy, although ketoconazole alone was subsequently used in three selected patients with cure. Four early deaths occurred in patients with delayed diagnosis and treatment, usually in association with other severe concurrent infections. We conclude that awareness of cryptococcosis is essential in immunocompromised hosts presenting with headache with, or without, mental confusion or fever.

Adolescent↗
PubMed1996

A latex cryptococcal antigen agglutination test for diagnosis and monitoring of therapy for cryptococcosis.

A latex cryptococcal antigen agglutination test (LCAT) was performed on sera obtained during the first 14 days of treatment from 58 animals (46 cats, 9 dogs, 2 koalas and 1 long billed corella) with cryptococcosis. The same commercial kit was used for all samples, and most serum samples were treated with pronase before testing. Sera from all 58 cases tested positive with the qualitative LCAT protocol (using undiluted sera), while sera from all 26 cats without cryptococcosis tested negative. Titres determined using the quantitative protocol ranged from 1 to > or = 131 072 (median titre between 2048 and 4096), with 57 of 58 cases (including all 8 animals that presented for neurological signs) having titres > or = 2 and thus considered positive according to the manufacturer's recommendations. The LCAT titre was positively correlated with disease severity (r = 0.4169; P = 0.0011), and patients with disseminated skin and/or lymph node involvement had significantly higher titres than those that did not (P = 0.0157). The presence of neurological signs, the species of the patient, concurrent viral disease (in cats) and the biotype of the isolate had no significant association with the LCAT titre. Cats that died of active cryptococcosis despite treatment did not have significantly higher titres (P = 0.3010) than those that responded to treatment. Sequential LCAT determinations obtained in 37 patients during treatment provided a useful quantitative indication of clinical progress, although the decline in titre lagged somewhat behind clinical improvement. Generally, the antigen titre declined by 2 to 4 fold per month during successful therapy. Although there are insufficient data to make unequivocal recommendations, we suggest that either antifungal therapy be continued until the LCAT titre declines to less than 1, or therapy be discontinued after a 32 fold or greater reduction in titre, with periodic monitoring of the serum antigen titre. Treatment of serum samples with pronase substantially increased the sensitivity of the LCAT.

Agglutination Tests↗
PubMed1990

Current status of cryptococcosis in Canada.

The concurrent use of microscopic, cultural, histopathologic and immunologic procedures enabled us to diagnose 91 cases of cryptococcosis, belonging to cutaneous, pulmonary, meningeal and disseminated types, from the time this mycosis was first reported in Canada in 1953 to the present. These cases occurred predominantly in Quebec (43%) followed by Alberta, British Columbia, Ontario, Saskatchewan, Manitoba, New Brunswick and Newfoundland. It is not known whether any Cryptococcus neoformans infections have occurred elsewhere in Canada. The clinical and laboratory findings indicate that infections occurred in debilitated as well as nondebilitated individuals. Nearly 25% of the infections were seen in individuals having the acquired immune deficiency syndrome (AIDS) in provinces of Alberta, British Columbia, Ontario and Quebec. In some of the AIDS cases, the latex agglutination (LA) test demonstrated exceptionally high titres of circulating cryptococcal antigen (1:256 to 1:32,768). Cr. neoformans infections occurred more commonly in males than in females, and there were 11 fatal cases of cryptococcosis. The incidence of Cr. neoformans in Canada is probably higher than our data suggest because cryptococcosis is not notifiable in Canada and underreporting is likely.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory Mycosis in Kyoto].

During the 7 years from 1990, thirty-two patients (20 in male and 12 in female, mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To clarify the essential points for early diagnosis of pulmonary cryptococcosis, we reviewed the clinical records and chest images. Three patients had a past history of pulmonary tuberculosis and eleven patients had underlying disorders such as malignancy, chronic pulmonary diseases and so on, but no HIV infection, which would affect this disease. Eighteen patients did not have any past history nor complications. The symptoms such as cough, sputum, chest pain and fever were generally of low-grade, 14 patients had no symptom at diagnosis. Except of some patients with severe infections and severe underlying disorders, laboratory findings such as inflamatory and nutritious markers were almost within near the normal range. On plain chest X-ray films the distribution of lesions was almost in proprtion to the volume of the lobes. The multifocal nudular and/or infitrative shadows wer observed in about 2/3 cases and single lesion in about 1/3. The width of lesions were minimal except of one case with interstitial pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the lesions were almost located in the outer zone, the lesions which were adjacent to the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the nodular/infitrative shadows were observed in three cases. Pulmonary cryptococcosis is air-borne and almost a chronic infection except in AIDS patients, so careful planning for examination is essential with considerations of the characteristics of clinical and imaging features of this infection.

Adult↗
PubMed1992

Efficacy and safety of amphotericin B colloidal dispersion compared with those of amphotericin B deoxycholate suspension for treatment of disseminated murine cryptococcosis.

The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated cryptococcosis. Mice were treated intravenously with either ABDS at 0.2, 0.8, or 3.2 mg/kg of body weight per dose or ABCD at 0.8, 3.2, 6.4, 12.8, or 19.2 mg/kg dose three times per week for 2 weeks. Excluding mice treated with ABDS at 3.2 mg/kg, which was acutely lethal in 100% of mice, and ABCD at 19.2 mg/kg, which also resulted in two early deaths, the survival of ABCD- and ABDS-treated groups was prolonged over survival of controls (P < or = 0.05). Survival of ABCD (3.2 mg/kg)-treated mice was improved over that of ABDS (0.2 mg/kg)-treated mice (P < 0.05); however, comparisons of mice given all other dosages of ABCD with mice given sublethal dosages of ABDS did not demonstrate differences in survival. Comparative fungal burdens in organs showed a decrease in liver (P < 0.05) and spleen (P < 0.05) burdens for ABCD with the 19.2-mg/kg therapy versus those with ABDS with the 0.8-mg/kg therapy and liver burdens for ABCD with the 12.8-mg/kg therapy versus ABDS with the 0.8-mg/kg therapy (P < 0.05). There was no difference in organ burdens between therapy with ABCD at 0.8 mg/kg and ABDS at 0.8 mg/kg. These data show that the efficacy of ABCD is equal to that of ABDS on a milligram-per-kilogram basis for murine disseminated cryptococcosis. Because of its decreased toxicity, greater efficacy with ABCD could be achieved through doses fourfold higher than the 100% lethal dose for ABDS. Thus, ABCD shows promise as an effective but less toxic alternative to ABDS for the treatment of disseminated cryptococcosis.

Amphotericin B↗
PubMed1968

Value and interpretation of serological tests for the diagnosis of cryptococcosis.

MAXIMAL SEROLOGICAL DIAGNOSIS OF CRYPTOCOCCOSIS MAY BE ACCOMPLISHED THROUGH THE CONCURRENT USE OF THREE TESTS: the latex agglutination (LA) test for cryptococcal antigen, and the indirect fluorescent antibody (IFA) and tube agglutination (TA) tests for Cryptococcus neoformans antibodies. These tests were applied to 141 serum and cerebral spinal fluid specimens from 66 culturally proven cases of cryptococcosis and to 42 sera from normal subjects and from patients with other systemic mycotic diseases. The LA test was sensitive and completely specific; of the sera from proven cases, 55% were positive. With the TA test, 37% of the specimens were positive and the test was highly specific. With the IFA test, 38% of the specimens were positive and the test appears to be the least specific of the three. Cross-reactions were most evident with blastomycosis and histoplasmosis case sera. When the three tests were used concurrently, 87% of the cryptococcosis case specimens were positive and permitted a presumptive diagnosis of C. neoformans infections in 61 (92%) of the 66 patients whose specimens were examined.

Amphotericin B↗