En las últimas semanas hemos tenido 2 casos de Criptococosis Meningea en pacientes HIV avanzados. En un caso el diagnóstico fue confirmado y en el segundo existe una fuerte sospecha y se está tratando como tal.
El siguiente artículo está incluido en una amplia revisión publicada en el CID.
Clinical Infectious Diseases 2005;40:S131-S235
This article is in the public domain, and no copyright is claimed.
1058-4838/2005/4005S3-0001
SUPPLEMENT ARTICLE
http://www.journals.uchicago.edu/CID/journal/issues/v40nS3/35615/35615.html
Treating Opportunistic Infections among HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America
Constance A. Benson,1 Jonathan E. Kaplan,2 Henry Masur,3 Alice Pau,3 and King K. Holmes4
1University of Colorado Health Sciences Center, Denver; 2Centers for Disease Control and Prevention, Atlanta, Georgia; 3National Institutes of Health, Bethesda, Maryland; 4University of Washington, Seattle
Cryptococcosis
Epidemiology. Virtually all HIV-1-associated cryptococcal infections are caused by Cryptococcus neoformans var neoformans. Before the advent of ART, approximately 5%–8% of HIV-1-infected patients in developed countries acquired disseminated cryptococcosis [352, 353]. The incidence has declined substantially with use of effective ART. The majority of cases of infection are observed among patients who have CD4+ T lymphocyte counts of <50>200 mm of water) in up to 75% of patients. Disseminated disease is a common manifestation, with or without concurrent meningitis. Approximately half of patients with disseminated disease have evidence of pulmonary rather than meningeal involvement. Symptoms and signs of pulmonary infection include cough or dyspnea and abnormal chest radiographs. Skin lesions might be observed.
Diagnosis. Cryptococcal antigen is almost invariably detected in the CSF at high titer in patients with meningitis or meningoencephalitis. Up to 75% of patients with HIV-1-associated cryptococcal meningitis have positive blood cultures; if disseminated or other organ disease is suspected in the absence of meningitis, a fungal blood culture is also diagnostically helpful. The serum cryptococcal antigen is also usually positive and detection of cryptococcal antigen in serum might be useful in initial diagnosis [354].
Treatment recommendations. Untreated cryptococcal meningitis is fatal. The recommended initial treatment for acute disease is amphotericin B, usually combined with flucytosine, for a 2-week duration followed by fluconazole alone for an additional 8 weeks (AI). This approach is associated with a mortality of <10%>200 mm H2O [355, 360]. In one large clinical trial, 93% of deaths occurring within the first 2 weeks of therapy and 40% of deaths occurring within weeks 3–10 were associated with increased intracranial pressure [360]. The opening pressure should always be measured when a lumbar puncture is performed [360].
The principal initial intervention for reducing symptomatic elevated intracranial pressure is repeated daily lumbar punctures (AII). CSF shunting should be considered for patients in whom daily lumbar punctures are no longer being tolerated or whose signs and symptoms of cerebral edema are not being relieved (BIII). Whether reducing opening pressure leads to a reduction in the mortality and morbidity associated with cerebral edema is unknown. No role exists for acetazolamide to reduce intracranial pressure (DIII).
Monitoring and adverse events. A repeat lumbar puncture to ensure clearance of the organism is not required for those with cryptococcal meningitis and improvement in clinical signs and symptoms after initiation of treatment. If new symptoms or clinical findings occur after 2 weeks of treatment, a repeat lumbar puncture should be performed.
Serum cryptococcal antigen is not helpful in management because changes in titer do not correlate with clinical response [354]. Serial measurement of CSF cryptococcal antigen might be more useful but requires repeated lumbar punctures and is not routinely recommended for monitoring response.
Patients treated with amphotericin B should be monitored for dose-dependent nephrotoxicity and electrolyte disturbances. Supplemental colloidal fluids might reduce the risk for nephrotoxicity during treatment (CIII). Infusion-related adverse reactions (e.g., fever, chills, renal tubular acidosis, hypokalemia, orthostatic hypotension, tachycardia, nausea, headache, vomiting, anemia, anorexia, and phlebitis) might be ameliorated by pretreatment with acetaminophen, diphenhydramine, or corticosteroids administered approximately 30 minutes before the infusion (CIII). Lipid formulations of amphotericin B are less toxic.
Azotemic patients receiving flucytosine should have their blood levels monitored to prevent bone marrow suppression and gastrointestinal toxicity; peak serum levels (2 hours after an oral dose) should be <100>100–200 cells/μL after ART. The numbers of such patients who have been evaluated remain limited. On the basis of these observations and inference from more extensive data regarding safety of discontinuing secondary prophylaxis for other opportunistic infections during advanced HIV-1 disease, discontinuing chronic maintenance therapy among such patients is a reasonable consideration (CIII). Certain HIV specialists would perform a lumbar puncture to determine if the CSF is culture-negative and antigen negative before stopping therapy even if patients are asymptomatic; other specialists do not believe this is necessary. Maintenance therapy should be re-initiated if the CD4+ T lymphocyte count decreases to <100–200 cells/μL (AIII).
Special considerations during pregnancy. Diagnosis and treatment for cryptococcosis among HIV-1-infected pregnant women are the same as for nonpregnant women. Considerations about the use of amphotericin B, fluconazole, and itraconazole are the same as those for mucocutaneous and invasive candidiasis (i.e., amphotericin B should be used in the first trimester to avoid the potential for teratogenicity with fluconazole or itraconazole).
Flucytosine is teratogenic in rats at high doses, but not at doses similar to human exposure [363]. No reports exist about its use in the first trimester of pregnancy in humans. Flucytosine might be metabolized to 5-fluoruracil. It should be used in pregnancy only if clearly indicated.
