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Cryptococcal Meningitis PowerPoint Presentation

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Description : Approach to Cryptococcal meningitis Management

Tags : health,cryptococcal,Cryptococcal Meningitis case

Published on : Mar 23, 2022 | Views : 2960 | Downloads : 10

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Slide 1-

Case study SB, 31yrs old female who is a known iss pt on HAART (TDF/3TC/EFV) and septrin who reports poor compliance and non adherence to medication Came with c/o of dyspnea at rest with minimal exertion. Also reports productive cough for >1month. She admits pleuritic chest pain. Denies PND and orthopnea but has low grade fever and episodes of sweating in the evening.
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Case study She has a persistent global headache that was not relieved by OTC analgesia not associated with photophobia. O/e J0A+C0O0L0D0 Vitals: BP-100/70mmhg, pulse 100bpm, temperature 380c, weight 38.5kgs Pt was OTPP, GCS 15/15 with positive kerning sign and neck stiffness
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ddx Bacterial Meningitis Chronic, benign lymphocytic meningitis Mycobacterium tuberculous infection Pnuemonia r/o PTB
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investigations Chest X-Ray – Normal CXR Lumbar puncture: No cells Total Protein: 0.58g/L, glucose 5.4 mmol/L; CL – 126 mmol/L (plasma glucose 9.6mmol/L)‏ Cryptococcal Ag - positive Cryptococcal culture – positive HIV test – positive CD4 count – Not Available
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Diagnosis?? Cryptococcal Meningitis.
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Cryptococcal meningitis Edwin chege
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Overview Cryptococcosis is a systemic mycosis caused by two environmental yeast species, Cr. neoformans and Cr. gattii. Cr. neoformans is distributed worldwide and is primarily an opportunistic pathogen, most commonly associated with HIV infection. Cryptococcosis is the most common fungal disease in HIV -infected persons, and it is the AIDS-defining illness for 60-70% of HIV-infected patients.
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Epidemiology The annual incidence of cryptococcosis in the United States is 2-7 cases per 1000 HIV-infected patients, with up to 89% occurring as a CNS manifestation. It is the fourth most common cause of opportunistic infections (after Pneumocystis jiroveci, cytomegalovirus [CMV], and mycobacteria). Its incidence has declined recently because of widespread use of antifungal and antiretroviral agents.
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Epidemiology Worldwide, it is estimated that approximately 1 million cases of HIV-associated cryptococcosis occur annually. In developed countries, the widespread use of highly active antiretroviral therapy (HAART) has lowered the incidence of cryptococcosis, but the incidence and mortality of the disease remain extremely high in areas with uncontrolled HIV disease and limited access to HAART or health care.
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Pathophysiology Cryptococcus neoformans spreads hematogenously to the CNS from pulmonary foci, which may be subclinical. In addition to invading the lung and CNS, cryptococci also invade the skin, bone, and genitourinary tract, but meninges appear to be the preferred site. The reasons are not clear, but several suggestions have been made. Cryptococcal disease usually develops only when CD4+ lymphocyte counts fall below 100 cells/mL. At this stage, macrophage function also is impaired.
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etiology Cryptococcus neoformans is a round or oval yeast, 4-6 mm in diameter, surrounded by a 30-mm-thick capsule. Patients with AIDS typically are affected by C neoformans serotype A.
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Clinical Presentation Headache (73-81%) Fever (62-88%) Malaise (38-76%) Nausea and vomiting (8-42%) Stiff neck (22-44%) Visual disturbances (30%) Altered mental status with somnolence (18-28%) Photophobia (19%) Papilledema (10%) Cranial neuropathies, including nystagmus and amblyopia (6%)
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CT and MRI CT scan is acceptable as a screening study, but MRI, with and without contrast, is the preferred diagnostic imaging modality. CT scan findings may be nonspecific or normal. Cryptococcal pseudocysts may appear as nonenhancing, hypodense lesions on CT scan. Twenty to thirty percent of patients show meningeal enhancement, parenchymal solid mass lesion without hemorrhage (granuloma), atrophy, cerebral edema, or hydrocephalus
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Primary Treatment If left untreated, cryptococcal CNS infections are fatal. Treatment with amphotericin B, flucytosine, fluconazole, and other antifungal agents greatly improves the prognosis, but a mortality rate of 6%, despite aggressive therapy, has been reported.
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Primary Treatment Amphotericin B deoxycholate (0.7-1.0 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally in 4 divided doses) for at least 2 weeks. This is followed by fluconazole (400 mg [6 mg/kg] per day orally) for a minimum of 8 weeks). Lipid formulations of amphotericin B (eg, liposomal amphotericin B [AmBisome], 6 mg/kg/day IV) can be substituted for amphotericin B. Liposomal amphotericin B may lead to quicker improvement with less renal toxicity. Flucytosine may be given intravenously in severe cases and in patients without oral intake.
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Primary Treatment In areas where flucytosine is unavailable, amphotericin B in combination with fluconazole (800-1200 mg/day) or voriconazole (300 mg twice daily) is an effective alternative in patients not receiving interacting medications.
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Maintenance Therapy Maintenance therapy should be continued with fluconazole 200 mg/day. Itraconazole 400 mg/day can be an alternative to fluconazole, but it is less effective.
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Maintenance Therapy Patients with cryptococcal disease who initiate HAART are at risk for cryptococcal immune reconstitution inflammatory syndrome (IRIS). Boulware et al found that in HAART-naive patients with AIDS and prior cryptococcal meningitis who developed IRIS after starting HAART, the cerebrospinal fluid tended to show less inflammation, with decreased CSF leukocytes (25 cells/mL or fewer), protein (50 mg/dL or less), interferon-gamma, interleukin-6, interleukin-8, and tumor necrosis factor-alpha, compared with patients who did not develop IRIS.
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Treatment of Relapse Consider salvage consolidation therapy with fluconazole (800–1200 mg/day orally), voriconazole (200–400 mg twice daily orally), or posaconazole (200 mg orally 4 times daily or 400 mg orally twice daily) for 10–12 weeks. If there are compliance issues and a susceptible isolate, prior suppressive doses of fluconazole may be reinstituted.
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Treatment of Increased Intracranial Pressure increased ICP (>250 mm H2 O) can be relieved by serial spinal taps. Decreasing intracranial pressure can rapidly improve headache, nausea, and vomiting.
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Special Considerations During Pregnancy The diagnosis of cryptococcal infections during pregnancy is similar to that in non-pregnant adults. Treatment should be initiated promptly after a diagnosis is confirmed. It should be emphasized that the postpartum period may be a high-risk period for the development of IRIS.
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Special Considerations During Pregnancy Lipid formulations of amphotericin B are the preferred initial regimen for the treatment of cryptococcal meningoencephalitis, disseminated disease, or severe pulmonary cryptococcosis in pregnant patients. Congenital malformations similar to those observed in animals, including craniofacial and limb abnormalities, have been reported in infants born to mothers who received fluconazole at doses of ≥400 mg/day or more through or beyond the first trimester of pregnancy.
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Special Considerations During Pregnancy However, in general azole antifungals should be avoided during the first trimester of pregnancy. Voriconazole and posaconazole are teratogenic and embryotoxic in animal studies, voriconazole at doses lower than recommended human doses; there are no adequate controlled studies in humans.
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Treatment summary
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Baseline renal impairment If patients have renal impairment at the time of diagnosis, this is not a contraindication to receiving amphotericin B deoxycholate at the standard dose (i.e. 1mg/kg/day); however, creatinine should be monitored frequently and if it deteriorates signifcantly, then amphotericin B may need to be stopped and treatment continued with ﬂuconazole monotherapy. When used as monotherapy during induction, the ﬂuconazole dose would be 1200 mg daily with normal renal function. With a creatinine clearance of 10 - 50 ml/min, the dose of ﬂuconazole used as monotherapy should be reduced by 50% to 600 mg daily, and if creatinine clearance is <10 ml/min, ﬂuconazole should be reduced to 400 mg daily
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Amphotericin B toxicity prevention, monitoring and management Major adverse eﬀects of amphotericin B deoxycholate include renal impairment due to renal tubular toxicity (usually in the second week of therapy), hypokalaemia, hypomagnesaemia, anaemia, febrile reactions and chemical phlebitis. Nephrotoxicity and electrolyte abnormalities may be prevented by pre-hydration, by avoiding concurrent use of other nephrotoxins (e.g. NSAIDs and aminoglycosides) and by routine administration of potassium and magnesium supplements.
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Prevention of amphotericin B deoxycholate-related toxicities Patients should be pre-hydrated with 1 litre of normal saline containing 1 ampoule of potassium chloride (20 mmol) infused over 2 hours before the amphotericin B infusion Twice-daily oral potassium and daily oral magnesium supplementation should be administered (adults)
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Monitoring Baseline and twice-weekly creatinine and potassium (and magnesium, if available) Baseline and weekly haemoglobin Fluid input and output monitoring
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Management of toxicities If creatinine doubles, then 1 dose of amphotericin B may be omitted or pre-hydration can be increased to1 litre 8-hourly. If creatinine remains elevated or repeatedly rises, then amphotericin B should be stopped and fluconazole used. Febrile reactions can be treated with paracetamol (1g) 30 minutes before infusion (if severe, hydrocortisone (25mg IV) can be given before subsequent infusions)
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Timing of ART among patients with CM Start ART 4 - 6 weeks after diagnosis of CM, not to be delayed beyond 6 weeks after diagnosis. In the latter trial, conducted in Uganda and SA, patients who started ART 1 - 2 weeks after CM diagnosis had a 15% higher mortality rate than those who deferred ART until 5 - 6 weeks. Another small trial showed possible excess IRIS in those patients who started early
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Timing of ART among patients with CM If nephrotoxicity occurred on amphotericin B, the renal function should be checked before starting ART to ensure that it has improved (creatinine clearance >60 ml/min) before commencing tenofovir. There are potential interactions between nevirapine and fluconazole, but studies have shown that these interactions do not affect the efficacy or toxicity of therapy
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Complications In patients with AIDS and other causes of immunosuppression who are infected with C neoformans, cure is often impossible, and patients require life-long suppressive therapy. In immunocompromised patients, the overall mortality rate following treatment of cryptococcal meningitis is approximately 25%-30%. Of those who survive, 40% have significant neurological deficits, including loss of vision, decreased mental function, hydrocephalus, and cranial nerve palsies. Relapse occurs in 20%-25% of patients.
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Prognosis CNS cryptococcosis is fatal unless treated. Several studies report acute mortality rates of 6-14%. A minority of patients die within the first 6 weeks after diagnosis, despite treatment. Those who survive usually live for longer than 18 months. In addition, the rate of relapse after treatment is high (30-50%).
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Prognosis Predictors of poor prognosis are controversial, but they have included the following: High CSF cryptococcal antigen titer (>1:1024) Minimal CSF pleocytosis Altered mental status at presentation Positive India Ink preparation Hyponatremia Positive cultures from extrameningeal sites
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Reference Davidsons Principles and practice of medicine_22Ed Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents https://aidsinfo.nih.gov/guidelines www.Medscape.com Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update by the Southern African HIV Clinicians Society
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Questions????
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Credits Dr. Nadia Aliyan Dr. Suchira Udagamasooriya