[CRYPTOCOCCAL MENINGITIS. RECENT OBSERVATIONS ON DIAGNOSIS AND TREATMENT].
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Amphotericin B↗
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Optic nerve sheath decompression for visual loss in patients with acquired immunodeficiency syndrome and cryptococcal meningitis with papilledema.
Visual dysfunction developing in association with acquired immunodeficiency syndrome (AIDS) can be multifactorial. Two patients with this syndrome and cryptococcal meningitis had papilledema and visual loss. Both were treated by optic nerve sheath fenestration. One patient had bilateral nonsimultaneous optic nerve sheath fenestrations; visual function improved in one eye. The other patient had bilateral visual improvement after a unilateral optic nerve sheath fenestration. Cryptococcal organisms were present in the dural sheath specimens of both patients despite ongoing therapy with antifungal medication. Postoperative orbital infectious complications did not occur. Autopsy examination of one patient showed that the sites of fenestration were patent. Medical treatment of cryptococcal meningitis associated with AIDS has a guarded prognosis. Optic nerve sheath fenestration offers a treatment alternative for papilledema and visual loss that occur with cryptococcal meningitis.
AIDS-Related Opportunistic Infections↗
Influence of the progression of cryptococcal meningitis on brain penetration and efficacy of AmBisome in a murine model.
BACKGROUND: AmBisome is a small unilamellar vesicle containing amphotericin B. AmBisome is generally unable to pass through the blood-brain barrier, but the distribution of AmBisome in the brain is increased by inflammation, and in consequence, AmBisome exhibits activity against fungal meningitis. We investigated the influence of the progression of cryptococcal meningitis on the brain penetration and efficacy of AmBisome. METHOD: Mice were infected intracerebroventricularly with Cryptococcus neoformans 4 h or 5 days prior to a single dose treatment. RESULTS: The brain tissue level and efficacy of AmBisome when administered 5 days after infection were greater than 4 h after infection. An immunohistochemical study showed that AmBisome-derived amphotericin B was localized at the infected site in the subarachnoid space. When AmBisome was compared with Fungizone at the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in both regimens. CONCLUSION: The brain penetration of AmBisome was enhanced by the progression of cryptococcal meningitis and correlated with the in vivo activity.
Amphotericin B↗
Cryptococcal meningitis complicating remote skull fracture.
A patient in whom cryptococcal meningitis complicated a nine year old depressed frontal skull fracture, an association which has not been reported previously, is recorded. This is also the first case of cryptococcal meningitis recognised in Ethiopia.
Adult↗
Cryptococcal meningitis: the place of itraconazole.
Itraconazole, an orally active broad-spectrum triazole antimycotic, has demonstrated anti-Cryptococcus activity in vitro and in animal models of cryptococcal meningitis. The drug has been used by a number of clinical groups for the treatment of cryptococcal meningitis, predominantly in AIDS patients. A problem that has been found with ketoconazole is the relatively low absorption of the drug in AIDS patients. This has resulted in ketoconazole plasma levels below the MIC90 (1-5 micrograms ml-1) needed to eliminate Cryptococcus neoformans. In addition, tissue levels of ketoconazole are lower than plasma levels. For itraconazole, the required MIC90 for Cr. neoformans is 0.1 microgram ml-1, and the plasma levels in AIDS patients receiving 200-400 mg daily, even in the case of reduced absorption, are well above this MIC90. The itraconazole levels in the brain and in the meninges are higher than the plasma levels. Consequently, itraconazole has been considered a valid candidate for studies in patients with cryptococcal meningitis. Various treatment modalities have been used: primary oral therapy alone or in combination with amphotericin B or 5-fluorocytosine (5-FC); maintenance oral therapy after initial treatment with amphotericin B (with or without 5-FC); and first-line intravenous treatment in severely ill patients. The results were evaluated in four different groups. When the drug was given as primary oral therapy without combination with amphotericin B or 5-FC, the results depended greatly on the dose administered and on the life expectancy of the patient at inclusion. In general, daily doses of 400 mg were better than 200-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS-Related Opportunistic Infections↗
Efficacy and adverse effects of higher dose amphotericin B monotherapy for cryptococcal meningitis in patients with advanced HIV infection.
Treatment with a low daily dose of amphotericin B (0.4 mg/kg) in AIDS patients with cryptococcal meningitis has been associated with low efficacy and high mortality. We report our successful clinical experiences on a higher daily dose of amphotericin B (0.8-1.0 mg/kg) monotherapy in treating cryptococcal meningitis from June 1994 to August 1997 in 13 cases of advanced HIV infection. Most of them (12/13) had at least one of several poor prognostic factors. The mean duration of amphotericin B administration was 26 days (range, 3 to 58 days). Both microbiologically and clinically successful rates of treatment at the end of amphotericin B therapy were high (85%, 11/13). The median duration of negative CSF culture post therapy was 17 days (range, 8 to 33 days). Bone marrow toxicities were; thrombocytopenia (46%) and significant anemia (92%) after a mean of 9 days of treatment. Both, impaired renal function and hypokalemia, were seen in 10 cases (77%), while elevation of amylase and lipase values were present in 6 cases (46%). Our report reveals that a higher daily dose of amphotericin B can achieve a high efficacy in treatment of cryptococcal meningitis in AIDS patients, even though most cases had poor prognostic factors and were in severe immunocompromised states. However, clinicians should monitor higher dose-related adverse effects carefully.
AIDS-Related Opportunistic Infections↗
A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.
To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.
AIDS-Related Opportunistic Infections↗
Maintenance therapy with itraconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome.
We conducted a prospective, open trial to establish the efficacy of itraconazole 400 mg/d as maintenance treatment for cryptococcal meningitis in AIDS patients. Between February 1996 and May 1997, 50 patients were included for analysis. After a mean follow-up of 326 days, 2 of 38 patients (5.3 per cent) had relapses of symptomatic cryptococcal meningitis. Hepatotoxicity occurred in 2 cases. In conclusion, maintenance therapy with itraconazole 400 mg/d is effective in preventing recurrent cryptococcal meningitis.
AIDS-Related Opportunistic Infections↗
Cryptococcal meningitis in non-HIV-infected patients.
There are few reports on cryptococcal meningitis in non-HIV-infected patients in subtropical areas. We reviewed 94 non-HIV-infected patients microbiologically diagnosed with cryptococcal meningitis and hospitalized at National Taiwan University Hospital, 1977-1996. Forty-two patients (44.7%) had underlying diseases. The main initial manifestations were headache (86.2%), vomiting (72.3%) and fever (69. 1%). The 30 patients with T-cell suppression had more acute illnesses (median duration of symptoms: 14 days vs. 29 days), less typical presentations of meningitis, and reduced inflammatory responses compared with the 64 without T cell suppression. There was no statistical difference between patients who received amphotericin B treatment for 10 weeks and those received amphotericin B with subsequent fluconazole treatment, in terms of mortality rate and recurrence rate. Seventy-five patients (79.8%) had satisfactory clinical responses, and two relapsed. Eighteen patients died (19.1%) and 10 of these died within 2 weeks of hospitalization. Patients in this series had outcomes comparable with those from temperate and even tropical countries with high percentages of immunocompetent hosts. Factors significantly associated with death were lymphoma, semicoma, leukocytosis, and initial high titres of cryptococcal antigen in cerebral spinal fluid (especially >/=1 : 512). On multivariate analysis, lymphoma and initial high cryptococcal antigen titres were independent predictors of mortality.
AIDS-Related Opportunistic Infections↗
The improved prognosis of cryptococcal meningitis with amphotericin B therapy.
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Amphotericin B↗
A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.
BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.
Acquired Immunodeficiency Syndrome↗
Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group.
BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.
Acquired Immunodeficiency Syndrome↗
[A case of hemiballismus during cryptococcal meningitis].
We present a case of hemiballismus related to cryptococcal meningitis. A 23 year-old man was hospitalized because of involuntary movements of his left side, confusion, hyperpyrexia, neck stiffness, bilateral papilledema, right hemiparesis and bilateral pyramidal signs. Diagnosis was made by CSF examination demonstrating cryptococci by india ink. CT with contrast showed hyperdense lesions in the head of the right caudate nucleus, in the left internal capsule and in the frontal and occipital lobes. After treatment with amphotericin B, 5-fluorocytosine and haloperidol, he experienced rapid recovery with disappearance of hemiballismus. To our knowledge, this is the first report of hemiballismus caused by cryptococcal meningitis.
Adult↗
[Significance of intracranial hypertension management in cryptococcal meningitis in patients with acquired immunodeficiency syndrome. Report of 2 cases].
Two cases of cryptococcal meningitis and increased intracranial pressure in patients with acquired immunodeficiency are described. Both patients presented high intracranial pressure that persisted despite optimal antifungal treatment (amphotericin B, 5-flucytosine initially, and fluconazole posteriorly). The elevated intracranial pressure produced headache, seizures, and reduced visual and auditory acuity. CAT scan demonstrated absence of ventricular dilatation or focal lesions. Both cases were treated with adequate antifungal therapy, as well as with repeated lumbar punctures and placement of a lumboperitoneal shunt due to the persistence of elevated intracranial pressure. One patient presented with unilateral loss of vision due to optic nerve atrophy. After one year of follow-up, one patient died due to progression of his disease, while the other is still alive and without evidence of neurological disease. Intracranial hypertension is a frequent clinical manifestation of cryptococcal meningitis in patients with acquired immunodeficiency syndrome (AIDS) that requires adequate diagnosis and management. Treatment should be directed towards the reduction of intracranial pressure though repeated lumbar punctures and, in some cases, with lumboperitoneal or ventricular-peritoneal shunts.
Acquired Immunodeficiency Syndrome↗
Elevated cerebrospinal fluid pressures in patients with cryptococcal meningitis and acquired immunodeficiency syndrome.
Increased intracranial pressure has been a noteworthy problem in some of our patients with cryptococcal meningitis and acquired immunodeficiency syndrome (AIDS), and this appears to be a feature observed in patients with cryptococcal meningitis reported in the literature. Whereas most attention of clinicians is presently focused on optimizing the antifungal regimen, so as to improve on high failure rates in cryptococcal meningitis in AIDS, little attention has been paid to the problem of intracranial hypertension. We argue that visual loss and some of the cases of death early after the onset of chemotherapy may be related to high cerebrospinal fluid (CSF) pressure, regardless of antifungal therapy. The possible pathophysiologic mechanisms are discussed, and we postulate that the mechanism is reduced CSF outflow possibly due to increased outflow resistance, not necessarily accompanied by prominent cerebral edema. Optimal therapy of this complication is not yet established, but some measures that may be helpful are ventricular shunting, frequent high-volume lumbar punctures, and possibly glucocorticoids.
Acquired Immunodeficiency Syndrome↗
Cryptococcal meningitis in immunocompetent patients.
Five cases of cryptococcal meningitis (CM) in immunocompetent patients who were initially diagnosed as either tuberculous meningitis or partially treated pyogenic meningitis are presented. There were 3 male and 2 female patients in the age range of 21 to 42 years. These patients presented as subacute meningitis. Additional features were visual impairment (4 cases), papilloedema (3 cases), sixth cranial nerve palsy (3 cases) and ataxic hemiparesis (one case). There was a mediastinal mass of fungal aetiology in one patient. While routine analysis of CSF showed a variable picture, it is the India ink preparation, test for cryptococcal antigen and culture for fungus which gave the diagnosis. These patients were treated with standard antifungal therapy. While one patient died and one patient recovered completely, three other patients were left with permanent visual impairment. It is concluded that CM is uncommon but an important cause of non-acute meningitis and should be included in the list of causes of preventable blindness.
Adult↗
Case Reports. Pulmonary cryptococcosis associated with cryptococcal meningitis in non-AIDS patients.
We report four cases of pulmonary cryptococcosis associated with cryptococcal meningitis in non-HIV infected patients. All four patients had no apparent symptoms and signs of focal lesions that necessitate evaluation for the pulmonary lesion. Two out of four patients had radiologic evidence of pulmonary cavitation and mass lesions simultaneously, an uncommon finding in non-AIDS patients. Diagnostic and therapeutic problems of pulmonary cryptococcosis associated with cryptococcal meningitis are discussed.
Adolescent↗
Lumbar drainage for control of raised cerebrospinal fluid pressure in cryptococcal meningitis: case report and review.
Raised intracranial pressure in the absence of ventricular dilatation is common in cryptococcal meningitis and associated with increased mortality. We report the case of a patient with HIV-associated cryptococcal meningitis, who developed increasing CSF pressure and visual impairment on therapy despite serial lumbar punctures. Insertion of a temporary lumbar drain controlled the opening pressure and resulted in full visual recovery. The advantages and necessary precautions with this approach are reviewed, and alternative protocols for the use of lumbar drains discussed.
AIDS-Related Opportunistic Infections↗