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Lana

Cryptococcal Meningitis

Introduction
Cryptococcus neoformans is an encapsulated yeast. Infection with the encapsulated yeast Cryptococcus neoformans a subacute or chronic infection which may affect the lungs or the skin but most commonly manifest as meningitis, especially in immunocompromised. Cryptococcosis represents a major life-threatening fungal infection in patients with severe HIV infection and individuals with suppressed immunity those receiving organ transplant, reticuloendothelial malignancy, corticosteroid treatment, or sarcoidosis.

Signs and symptoms
The presentation in cryptococcosis varies with the site of infection and the patient’s immune status. Signs and symptoms of pulmonary cryptococcosis in immunocompetent patients are as follows:
•    Cough (54%)
•    Cough with the production of scant mucoid sputum (32%)
•    Pleuritic chest pain (46%)
•    Low-grade fever, dyspnea, weight loss, and malaise (less common)

HIV-infected patients with pulmonary cryptococcosis may present with the following:
•    Fever (84%)
•    Cough (63%)
•    Dyspnea (50%)
•    Headache (41%)
•    Weight loss (47%)

Other possible findings in pulmonary infection are as follows:
•    Pleuritic pain
•    Hemoptysis
•    Rales or pleural rub
•    Acute respiratory distress syndrome (ARDS)

HIV-infected patients may have minimal or nonspecific symptoms. Common symptoms are as follows:
•    Headache
•    Confusion
•    Lethargy
•    Obtundation
•    Coma
•    Normal or mildly elevated temperature
•    Nausea and vomiting (with increased intracranial pressure)
•    Fever and stiff neck (with an aggressive inflammatory response; less common)
•    Blurred vision, photophobia, and diplopia
•    Hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements
 
After lung and CNS infection, the next most commonly involved organs in disseminated cryptococcosis include the skin, the prostate, and the medullary cavity of bones. Cutaneous manifestations (10-15% of cases) are as follows:
•    Papules, pustules, nodules, ulcers, or draining sinuses
•    Umbilicated papules in patients with AIDS
•    Cellulitis with necrotizing vasculitis in organ transplant recipients

Other less common forms of cryptococcosis include the following:
•    Optic neuritis or endophthalmitis
•    Myocarditis
•    Chorioretinitis
•    Hepatitis
•    Peritonitis
•    Renal abscess
•    Myositis
•    Adrenal involvement

Diagnosis
The workup in patients with suspected cryptococcosis includes the following:
•    Cutaneous lesions: Biopsy with fungal stains and cultures
•    Blood: Fungal culture, cryptococcal serology, and cryptococcal antigen testing
•    Cerebrospinal fluid: India ink smear, fungal culture, and cryptococcal antigen testing
•    Urine and sputum cultures, even if renal or pulmonary disease is not clinically evident
•    In AIDS patients with cryptococcal pneumonia, culture of bronchoalveolar lavage washings

With possible CNS cryptococcosis, especially in patients who present with focal neurologic deficits or a history compatible with slowly progressive meningitis, obtaining a CT or MRI scan of the brain prior to performing a lumbar puncture.

With pulmonary cryptococcosis, radiographic findings in patients who are asymptomatic and immunocompetent may include the following:
•    Patchy pneumonitis
•    Granulomas ranging from 2-7 cm
•    Miliary disease similar to that in tuberculosis
 
Treatment
Pulmonary cryptococcosis resolves without specific therapy in most immunocompetent patients. Antifungal therapy is necessary for the following:
•    Pulmonary cryptococcosis in immunosuppressed hosts
•    CNS cryptococcosis
•    Disseminated nonpulmonary non-CNS cryptococcosis
 
Treatment for cryptococcal meningitis in patients with AIDS is as follows:
•    Amphotericin B, 0.7-1 mg/kg/day for 2 weeks, with or without
•    Flucytosine, 100 mg/kg/day in 4 divided doses for 2 weeks
•    Flucytosine speeds clearance of viable yeast from CSF but is potentially toxic, especially in patients with renal dysfunction
•    After 2 weeks, fluconazole at 400 mg/day for a minimum of 8-10 weeks
Alternative initial therapies include the following:
•    A lipid formulation of amphotericin B, 4-6 mg/kg/day for 3 weeks
•    Fluconazole, 400-800 mg/day plus flucytosine for patients unable to tolerate amphotericin B

Guidelines published in 2000 recommended maintenance therapy with fluconazole at 200 mg/day for life.[1] Guidelines published in 2002 supported discontinuation of suppressive therapy if CD4 counts remained greater than 200 cells/µL but reinstitution if the CD4 counts fall to fewer than 200 cells/µL.[2]

Management of intracranial pressure in cryptococcal meningitis is as follows:
•    Monitor CSF pressure during the initial phase of therapy
•    If the opening pressure exceeds 250 mm H 2 O, remove CSF to reduce the closing pressure to below 200 mm H 2 O or at least 50% of the elevated opening pressure

In patients without AIDS, treatment of cryptococcal meningitis is as follows:
•    Amphotericin B (0.7-1 mg/kg/day) alone for 6-10 weeks or in combination with flucytosine (100 mg/kg/day in 4 divided doses) for 2 weeks, followed by fluconazole for a minimum of 10 weeks
•    Base therapy duration on CSF examination results
•    Consider weekly CSF examination until culture conversion is documented and cultures remain negative for 4 weeks
•    CSF protein abnormalities may persist for years despite successful therapy; thus, an elevated CSF protein as the only residual abnormality should not dictate prolonging therapy
Pulmonary cryptococcosis can be treated with observation only, if the following criteria are met:
•    CSF chemistry parameters are normal
•    CSF culture, India ink preparation, and serology results are negative
•    Urine culture results are negative
•    The pulmonary lesion is small and stable or shrinking
•    The patient has no predisposing conditions for disseminated disease

Antifungal treatment for cryptococcal pulmonary disease is as follows:
•    Mild-to-moderate disease: Fluconazole for 6-12 months, itraconazole for 6-12 months, or amphotericin B
Severe disease: Amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day) for 6-10 weeks, or for 2 weeks followed by fluconazole at 400 mg/kg/day for at least 10 weeks, possibly followed by further consolidation therapy for 6-12 months.

Summary
Cryptococcal meningitis is a common opportunistic infection in AIDS patients. Cases also occur in patients with other forms of immunosupression and in apparently immunocompetent individuals. Mortality from HIV-associated cryptococcal meningitis remains high (10–30%), even in developed countries, because of the inadequacy of current antifungal drugs and the complication of raised intracranial pressure. In cohorts of HIV-infected patients from sub-Saharan Africa, cryptococcosis has accounted for 13–44% of all deaths. Optimal current therapy is with amphotericin B 0.7–1 mg/kg/day plus flucytosine 100 mg/kg/day for 2 weeks, followed by fluconazole 400 mg/day for 8 weeks and 200 mg/day thereafter.

References
•    1. [Guideline] Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis. 2000 Apr. 30(4):710-8.
•    2. [Guideline] Kaplan JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002 Jun 14. 51:1-52.

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Metabolism

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Motility Test

Motility is the ability of an organism to move by itself by means of propeller like flagella unique to bacteria or by special fibrillation that produce a gliding form of motility.