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PubMed1999

Cryptococcal meningitis in renal transplant patients associated with environmental exposure.

Fungal infections in renal transplant recipients are less common than bacterial infections; however, the morbidity from fungal infections is high. There is limited information in the literature concerning post-transplantation cryptococcal infection due to environmental exposure of patients living in high-risk areas. We report three patients who were diagnosed with cryptococcal meningitis after kidney transplantation. Cryptococcal titers prior to transplant surgery were negative in all three patients. These patients all lived in rural areas and demonstrated evidence of environmental exposure leading to subsequent cryptococcal meningitis. All patients had exposure to pigeon and chicken excreta and, after treatment, two patients are alive and well with excellent allograft function. The third patient has marginal renal function but is currently not on dialysis. Early diagnosis is essential for salvage from these potentially lethal infections. Intense headache was a prominent feature in the clinical presentation of our patients, and should signal the need for early sampling and culture of spinal fluid. Meningismus was not present in any of our patients, even when other systemic symptoms were identified. We recommend a high index of suspicion post-transplantation for all patients who may have environmental or occupational exposure to cryptococcus. If infection is detected quickly and treatment instituted promptly, patient recovery and allograft survival are possible. Long-term therapy with fluconazole, a non-nephrotoxic agent, should permit eradication of the infection with preservation of kidney function.

Amphotericin B↗
PubMed1991

Profound papilledema due to cryptococcal meningitis in acquired immunodeficiency syndrome: successful treatment with fluconazole.

Although cryptococcal meningitis is a frequent infection in patients with AIDS, papilledema is rarely reported. We have reported a case of profound papilledema associated with cryptococcal meningitis in a patient with AIDS. After treatment failure with amphotericin B, the patient was successfully treated with fluconazole, and the papilledema resolved.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Cryptococcal meningitis after liver transplantation.

We present our experience with 10 liver transplant recipients in whom cryptococcal meningitis developed after liver transplantation. Disease developed a median period of 3.5 months (range, 2-36 months) after transplantation and patients were diagnosed a median period of 9 days (range, 2-90 days) after initial symptoms. Headache, fever, and mental status changes were the most frequent clinical presentations, while meningismus was found in only 30% of patients. Cerebrospinal fluid analysis was diagnostic in all cases. All patients were treated with amphotericin B and flucytosine. Immunosuppression was either decreased or discontinued during therapy. Five patients died, four as a direct result of cryptococcal infection and one as a result of chronic rejection. Three patients had long-term survival without any sequelae. One long-term survivor suffered blindness consequent to the disease. We conclude that cryptococcal meningitis is a rare complication in liver transplant recipients (0.25%), and has a high mortality rate (50%). Early recognition, combination antifungal therapy, and decrease or discontinuation of immunosuppression are important for cure. No relapse has been seen in surviving patients.

Adult↗
PubMed2006

Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole.

BACKGROUND: AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999-2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. METHODS: Retrospective chart review of adult patients before and after the fluconazole donation. RESULTS: 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days - their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. CONCLUSION: Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

AIDS-Related Opportunistic Infections↗
PubMed1992

Itraconazole in the treatment of cryptococcal meningitis.

The results of an open study of the efficacy of oral itraconazole therapy in 8 patients with cryptococcal meningitis are reported. Therapy is monitored by clinical response with culture, indian ink stain and cryptococcal antigen testing of CSF. Four (50%) of eight patients were cured, two (25%) had partial response, and two (25%) failed. One patient had a relapse but responded to retreatment. No toxicity was observed. Itraconazole is, therefore, suggested as a new treatment for cryptococcal meningitis.

Adolescent↗
PubMed2001

Case report. Recurrence of increased intracranial pressure with antiretroviral therapy in an AIDS patient with cryptococcal meningitis.

We present the case of an AIDS patient with cryptococcal meningitis who, after an excellent clinical and mycological response to antifungal therapy, developed an exacerbation of signs and symptoms, including elevated intracranial pressure and an increase in cerebrospinal fluid cryptococcal antigen and white blood cells, following the initiation of highly active antiretroviral therapy (HAART). Cultures yielded no growth and the patient responded to repeated lumbar punctures without changing or intensifying antifungal therapy. To our knowledge, this is the first report of symptomatic elevated intracranial pressure occurring during HAART-related immune recovery in a patient with cryptococcal meningitis. Exacerbation of symptoms does not necessarily reflect mycological failure that requires a change in antifungal therapy, but may relate to acutely increased intracranial pressure that will respond to simple measures, such as repeated lumbar punctures.

AIDS-Related Opportunistic Infections↗
PubMed1988

Management of cryptococcal meningitis in patients with AIDS.

A case of cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome (AIDS) is described, as well as the epidemiology, pathogenesis, clinical manifestations, diagnosis, and therapeutic management of the disease. In July 1987 a 38-year-old white man was admitted to the hospital because of confusion, disorientation, and headache. His medical history was notable for a positive human immunodeficiency virus test. Culture of the cerebrospinal fluid was positive for Cryptococcus neoformans. The patient was started on amphotericin B 16 mg/day (0.3 mg/kg/day) intravenously and flucytosine 2 g every six hours (150 mg/kg/day) orally. Despite premedication with diphenhydramine and acetaminophen, he experienced rigors that were treated with hydrocortisone and meperidine. Three weeks later he was discharged on flucytosine 2 g orally every six hours and amphotericin B 50 mg intravenously every other day. One week later the patient developed fever and chills; blood cultures were positive for methicillin-sensitive Staphylococcus aureus, and his peripheral leucocyte count was 1.8 X 10(3)/cu mm. Flucytosine was discontinued, and he was treated with intravenous nafcillin while remaining on amphotericin B. In October the patient complained of nausea, vomiting, weakness, and agitation. A CSF latex agglutination titer for cryptococcal antigen was 1:32. He was treated with amphotericin B 50 mg daily until symptoms resolved and then continued on amphotericin B 50 mg twice weekly. Cryptococcosis is the most common life-threatening fungal infection among AIDS patients. In contrast to immunocompetent hosts, this population invariably develops disseminated disease, with 85% having meningeal involvement. The most effective therapy for cryptococcal meningitis in patients with AIDS has not been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1982

Long-lasting, specific immunologic unresponsiveness associated with cryptococcal meningitis.

A sensitive radioimmunoassay and an antibody class-specific enzyme-linked immunosorbent assay were used to determine whether patients cured of cryptococcosis responded normally to immunization with cryptococcal capsular polysaccharide (CPS) and type III pneumococcal polysaccharide. 10 normal volunteers and 8 patients who had been cured of cryptococcal meningitis and who had been cured of cryptococcal meningitis and who had no serious underlying diseases were immunized with both antigens. Geometric mean titers to CPS measured by radioimmunoassay were 1:1 in both groups before vaccination, but were 1:3 in patients and 1:119 in controls following immunization (P less than 0.01, Student's t test). Analysis of the class-specific response to immunization with CPS found little anti-CPS IgG or IgA. Geometric mean postvaccination IgM titers were 1:31 in patients and 1:238 in controls (P less than 0.01). Responses to immunization with type III pneumococcal polysaccharide were similar in patients and controls, with IgA, IgM, and IgG mean titers of 1:1129, 1:369, and 1:158 in patients and 1:1504, 1:1039, and 1:163 in controls (P greater than 0.2 for each antibody class). Cured cryptococcal meningitis is often associated with prolonged specific immunologic unresponsiveness.

Adolescent↗
PubMed1981

Cryptococcal meningitis: treatment of three patients with miconazole.

Three patients with cryptococcal meningitis who were treated with miconazole are reported. All patients had previously received combination therapy with amphotericin B and flucytosine which was unsuccessful. All patients showed clinical improvement, and one obtained a mycological remission. Miconazole was well tolerated, and would appear to be a relatively non-toxic and effective drug in the treatment of cryptococcal meningitis which is refractory to conventional chemotherapy.

Adult↗
PubMed1996

[A case of AIDS with intractable cryptococcal meningitis].

A 38-year-old hemophiliac, who had been infected with HIV by the administration of blood products and had been diagnosed as AIDS by the onset of Pneumocystis carinii pneumonia, was admitted to our hospital with the complaints of headache and vomiting. After he was diagnosed as cryptococcal meningitis using the microscopy, cryptococcal antigen detection and culture of cerebrospinal fluid, treatment with amphotericin-B and fluconazole was started. As there was no clinical improvement, spinal drainage was performed and acetazolamide administered in order to reduce the intracranial pressure. Treatment was changed from AMPH-B and FLCZ to a combined therapy of AMPH-B and itraconazole. As his clinical features showed improvement, he was discharged home on a maintenance dose of ITCZ and acetazolamide after having been hospitalized for three months. This case-report may be of use in the management of cryptococcal meningitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2000

Antifungal therapy for treatment of cryptococcal meningitis.

OBJECTIVE: To compare the curative effects of three different antifungal regimens in the treatment of cryptococcal meningitis. METHODS: Twenty-two patients were divided into 3 groups: Group I was given intravenous amphotericin B alone or combination with flucytosine therapy. Group II received intravenous fluconazole alone or combination with flucytosine. The treatment of Group III was divided into two steps, where the patients received intrathecal amphotericin B plus intravenous amphotericin B with or without intravenous fluconazole until the mycological culture of cerebrospinal fluid (CSF) turned negative, followed by oral fluconazole or itraconazole as maintenance therapy until direct microscopic examination of CSF showed negative once a week for three consecutive weeks. RESULTS: Of the twenty-two patients, 17 (77.3%) were cured, 2 (9.1%) improved, 3 (13.6%) died, and one (4.5%) relapsed. Of the 8 patients in Group I, 5 were cured, 2 improved, one died and one relapsed; Of the 4 patients in Group II, 2 were cured, and 2 died; All the 10 patients in Group III were cured without any recurrence. CONCLUSION: The two-step therapeutic regimen may be suited to the treatment of cryptococcal meningitis.

Adolescent↗
PubMed1996

Raised ICP in a child with cryptococcal meningitis: CT evidence of a distal CSF block.

Raised intracranial pressure (ICP) often complicates the course of cryptococcal meningitis. The pathogenesis of the severely raised cerebrospinal fluid (CSF) pressure commonly associated with this condition is largely unexplained, because the majority of patients have normal cranial computed tomographic (CT) findings when diagnosed. We report a case of cryptococcal meningitis in a child who had severely raised CSF pressure on admission, and in whom repeated CT scanning showed progressive enlargement of the subarachnoid space and ventricular system during the course of treatment. The normalization of these spaces after ventriculoperitoneal (VP) shunting suggests a distal CSF block as the cause of the raised ICP in this patient. The CSF pressure was monitored and treatment with oral acetazolamide and furosemide resulted in a definite, but slow and incomplete lowering of ICP. Intrathecal therapy with hyaluronidase had no beneficial effect on either ICP or the degree of visual loss.

Cerebrospinal Fluid↗
PubMed1995

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗
PubMed1993

Cryptococcal meningitis and AIDS.

Dr. William G. Powderly provides a comprehensive review of the state of our knowledge regarding cryptococcal infection in persons with infection due to human immunodeficiency virus type 1. The introduction of fluconazole and itraconazole increased insight into prognostic factors affecting these patients. The need to suppress this fungal infection in individuals with impaired immunity has greatly altered the management of cryptococcal meningitis; therapy for this condition was established by the landmark study conducted by the Mycosis Study Group in 1979 (Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in treatment of cryptococcal meningitis. N Engl J Med 1979;301:126-31). In this AIDS commentary Dr. Powderly clearly outlines the progress made through clinical investigations and the problems that remain to be resolved.

AIDS-Related Opportunistic Infections↗
PubMed2002

Use of ventriculoperitoneal shunts to treat uncontrollable intracranial hypertension in patients who have cryptococcal meningitis without hydrocephalus.

Between 1997 and 2000, 4 human immunodeficiency virus-negative patients in our institution had cryptococcal meningitis with uncontrollable intracranial hypertension. All 4 patients were treated with antifungal drugs as well as ventriculoperitoneal (VP) shunts for intracranial hypertension. Neurological deficits that were unresponsive to pharmacologic treatment were resolved by use of the VP shunt. Uncontrollable elevation of intracranial pressure associated with cryptococcal meningitis can be resolved by use of a VP shunt, even when imaging studies do not reveal hydrocephalus.

Adult↗