Clinical case by uMYwGu

VIEWS: 12 PAGES: 33

									    UCSD I-TECH AETC
                        Telemedicine Series

Cryptococcal Meningitis: Management

                Helder Lopes, M.D.
        Maputo Central Hospital, Mozambique
                   13 June 2011



  ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing
  Medical Education to provide continuing medical education for physicians.The University of California, San Diego School of Medicine designates this
  educational activity for a maximum of one credit per hour AMA PRA Category 1 Credits™.

  Physicians should only claim credit commensurate with the extent of their participation in the activity.
           Case Presentation: D.I
•   62 yo HIV+ male, not on ART
•   Admitted to hospital with headache
•   Altered mental status, no seizures
•   No fever, cough, shortness of breath
•   No gastrointestinal symptoms
•   No urinary symptoms
                 Physical Exam
•   Gen: in coma (GCS 3+3+2=8/15), pale, hydrated
•   HEENT: No icterus, +oral candidiasis, no ulcers
•   Neck: No lymphadenopathy
•   Cardiac: PMI at left 5th intercostal space, no
    murmurs
•   Resp: No cyanosis, crackles or rhonchi
•   Abd: no hepatosplenomegaly, no ascites, no
    asterixis
•   Ext: No edema
•   No cutaneous lesions
            Neurological exam
•   Coma (GCS 8/15 as mentioned previously)
•   +nuchal rigidity
•   Kernig positive
•   Brudzinsky positive
•   Normal reflexes
•   Negative Babinski
•   Motor and sensory exam limited by AMS
                 Problem List
•   HIV infection, untreated
•   Altered mental status
•   Meningeal signs
•   Suspected anemia (pallor)
•   Oral candidiasis
               Lab tests(blood)
•   Wbc-3.200/ml
•   Hb-8.4 g/dl
•   Plt-132000/ml
•   MCV-81.1
•   Neutrophils-2800/ml
•   Lymphocytes-200ml
•   Blood Culture-negative
•   Malaria tests-negative
•   VDRL Negative
              Lab Tests (blood)
•   Na-129mmol/l -(135-147mmol/l)
•   K-3.9mmol/L-(3.5-5.6mmol/l)
•   Urea-6.1mmol/L (3.3-6.7mmol/l)
•   Creatinine-80.5 umol/L (80-115umol/l)
•   Glucose-6.5mmol/L (3.5-6.5mmol/l)
•   TIBC -154ucg/dl-(240-410ucg/dl)
•   Ferritin -600ug/dl-(250-450ug/dl)
•   Iron-35ug/dl -(35-115ug/dl)
              Lab tests (blood)
•   AST-39-(37)
•   ALT-34-(43)
•   Total Bil-1.3mg/dl (1.2mg/dl)
•   Direct Bil-0.4mg/dl (0.4 mg/dl)
•   GGT-39U/l- (13-45U/l)
•   Albumin-34 mg/dL (35-50 mg/dl)
•   Total protein-60 mg/dL (58-89mg/dl)
                  Other Tests
•   Fundoscopy normal
•   CD4 = 27(07%)
•   Non-contrast head CT scan normal
•   No contraindication for Lumbar puncture
•   Urinalysis normal
•   Chest –Xray-No infiltrate,no intrathoracic
    adenophaty,no pleural effusion
                        CSF
• Clear, Unable to measure opening pressure(no devices)
• Glucose-48 mg/dL(45-80mg/dl),Protein-0.66 g/dL(0.45
  mg/dl),Cl-117mEq/l(115-127mEq/l)
• No cells
• Cryptococcus –Antigen + (titer not available)
• Culture –No bacterial growth
• AFB culture- Negative
• VDRL -Negative
• Culture –Cryptococcus +(Sensitivity-95-100%)(8)
• Indian Ink positive-sensitivity-80%(9)
                Diagnosis
• Cryptococcal Meningitis
• AIDS (CD4=27)
• Mild Normocytic Anemia (Cronic Disease?)
             Initial Treatment
• Amphotericin B (0.7mg/Kg/dia)
• Flucitosine ,Lipossomal Anfotericine B and
  Itraconazol no available
• Normal saline
• Lumbar puncture every 2 days to decrease
  pressure (with removal of 30 ml of CSF each
  time).Is it useful?What was initial pressure?
               Hospital Day 3
•   Glasgow 3+3+3=9/15
•   Na-143 mmol/L(
•   K-3.9 mmol/L
•   Urea-11 mmol/L
•   Creatinine-260 mmol/L
•   Glucose-6.6 mmol/L
             Hospital Day 5

• Glasgow 3+4+3=10/15
• But....
• CSF –Gluc35 Prot-44 Cel 3
                       Day 5
•   Na-130mmol/l
•   K-4.4mmol/l
•   Urea-15mmol/l
•   Creatinine-640mmol/l
•   Glucose-9.1mmol/l
•   Acute renal failure caused by amphotericin B?
•   Urine output 1500 ml/day
•   Stoped Amphotericin B
•   Started IV Fluconazole 400 mg every 8
    hours(NEPHROTOXICITY?)
              Hospital Day 11
•   Glasgow 4+3+4=11/15
•   Creatinine-332mmol/L
•   K-4.0mmol/L
•   Seems to improved mentaly
•   Urine output 1900 ml/day
            Hospital Day 14
Creatinine -116 mmol/L
BUT pt had developed:
• Cough
• Fever (38,5°C)
• Dyspnea
• Bilateral Crackles
• SPO2-90%
• Low Blood Pressure (80/40mmHg)
                   Diagnosis
•   Pneumonia Hospital Acquired
•   Sepsis
•   Not possible to check LDH
•   Started ceftriaxone 1gr twice a day
               Hospital Day 15
•   Creatinine-200mmol/L
•   Na -143 mmol/L
•   K-4.5 mmol/L
•   Urea 6.3 mmol/L
•   Glucose-5.5 mmol/L
•   Acute renal failure secondary to sepsis?
              Hospital Day 20
•   No fever
•   Mild cough
•   SpO2 -99%
•   Blood Pressure -130/80mm Hg
•   Blood culture negative
•   Sputum culture negative
•   Creatinine-60.9mmol/L
•   Patient started on d4T/3TC/NVP
             Hospital Day 25
• Glasgow 3+2+2=7/15
• CSF became turbid (secondary infection?)
• CSF: no cells, normal glucose and proteins
• CSF culture –positive for Cryptococcus
  neoformans
• Criptococcal Antigen titers on CSF-Not
  available
• Blood culture negative
                   Day 30
• CSF culture positive for Cryptococcus
  neoformans
• Lumbar puncture –High
  pressure?(ventriculostomy or
  ventriculoperitoneal shunt?)
                                Summary
Hospital       1        3       5        11       14       15        20       25
Day
Urea          6.1      11       15        7       6.0      6.3      5.0       5.6
Creatinine    80.5     260     640       332      116      200      60.9
GCS           8/15    9/15     10/15    11/15    11/15    10/15     9/15     7/15
Symptoms      +++      No       No       No      Resp      No        No       No
UOP          normal   1000     1500     1900     1110     2000      1450     1500
CSF prot      0.48             0.44      0.29     0.50              0.40      0.35
CSF gluc      0.66              35       50                          69       60
CSF cells      0                3         3        2                 7         0
CSF CRAG       +                +         +        +                 +         +
Crypto Cx      +                +         +        +                 +         +
Treatment    Ampho    Ampho   Ampho     Flucon   Flucon   Flucon   Flucon,   Flucon
                              flucon                                ART
 Cryptococcal Meningitis in Resource-
        constrained Settings
• Topics:
• Diagnosis
• Treatment
  – Anti-fungal therapy
  – Management of increased intracranial pressure
                         Diagnosis
• Serum should be tested for the presence of Cryptococcal
  polysaccharide antigen;
   – Serum Cryptococcal antigen is positive in more than 99% of
     patients with cryptococcal meningitis (Disseminated
     Criptococcosis)
• Routine CSF studies should include
   –   Measurement of opening pressure
   –   Fungal cultures
   –   Gram stain and routine culture
   –   India ink smear
   –   Measurement of CSF Cryptococcal antigen titer
   –   Glucose concentration
   –   Protein concentration
   –   Cell count with differential
   –   AFB –Culture
         Anti fungal-treatment
• Cryptococcal meningitis is fatal if untreated. In
  patients with AIDS, a regimen of intravenous
  amphotericin B (0.7 mg per kg) for 2 weeks,
  followed by oral fluconazole (400mg) for
  another 8 weeks, has produced the best
  outcome to date, in prospective trials.
  – The mortality rate was less than 5-15% (6)
            Antifungal Treatment
• Addition of flucytosine to amphotericin B during the
  first 2 weeks of treatment may improve outcomes
   – Trend toward a better CSF sterilization rate, as 60% of
     patients receiving amphotericin B plus flucytosine were
     culture negative at 2 weeks, compared with 51% of
     patients who received amphotericin B alone.
   – Furthermore, the use of flucytosine as initial therapy has
     been associated with a decreased risk of later relapse of
     cryptococcal meningitis
           Antifungal Treatment
• Therapy with the azoles (fluconazole or itraconazole)
  alone is not optimal initial treatment, since response
  rates in all prospective trials have been less than
  50%(3).
• The initial experience with the combination of
  fluconazole (400 mg per day) with flucytosine (150 mg
  per kg per day) as primary treatment resulted in
  promising response rates in selected patients
• Combination of flucytosine and high doses of
  fluconazole (800 to 2000 mg per day) are associated
  with initial response rates of over 70%, which is
  comparable to the rates seen in trials of amphotericin
  B plus flucytosine.(3)
           Management of ICP
• Repeated CSF opening pressure measurement is
  essential.
• Lumbar puncture with ample CSF removal, while
  contraindicated in other conditions with raised
  intracranial pressure, may be required in AIDS-
  related Cryptococcal meningitis with acute life-
  threatening CSF pressure elevation, even with a
  normal CT scan of the head
• Medical approaches, including the use of
  corticosteroids, acetazolamide, or mannitol, have
  NOT been shown to be effective in the setting of
  elevated intracranial pressure in cryptococcal
  meningitis
         Poor Prognosis factors(9)
•   Abnormal mental status
•   High Opening pressure?
•   Low CSF Glucose level
•   Low WBC on CSF
•   Initial Indian ink positive
•   High titers of Cryptococcal Antigen(1:32)?
•   Extra-CNS culture positive sites?
            Some questions
• Did the patient have a relapse or terapeutic
  failure?
• How to Check Pressure whe not available own
  devices?
• How to treat a patient from now?
  References: Cryptococcal Meningitis
• (1).Cryptococcal meningitis in patients with AIDS
• (2).WE Dismukes - Journal of Infectious Diseases, 1988
• (3).Powderly WG. Cryptococcal meningitis in HIV-infected patients.
  Current Infectious Disease Reports 2000, 2:352–357
• (4).Gambarin KJ, Hamill RJ. Management of increased intracranial
  pressure in cryptococcal meningitis. Current Infectious Disease
  Reports 2002, 4:332–338

• (5).Saag MS, Graybill RJ, Larsen RA, et al.: Practice guidelines for
  the management of cryptococcal disease. Clin Infect Dis 2000,
  30:710–718
• (6).Swartz MN. Meningitis: bacterial, viral, and other. In: Goldman L,
  Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders
  Elsevier; 2007:chap 437
• (7)Clinical Infectious Diseases Vol. 22, No. 5, May, 1996
 References: Cryptococcal Meningitis
• (8)Zuger, A., E. Louie, S. R. Holzman, and S. M.
  Simberkoff. 1986. Cryptococcal disease in
  patients with the acquired immunodeficiency
  syndrome. Ann. Intern. Med. 104:234-240.
• (9) Diamond, R. D., and J. E. Bennett. 1974.
  Prognostic factors in cryptococcal meningitis: a
  study in 111 cases. Ann. Intern. Med. 80:176-181.

								
To top