Morning Report: Cryptococcal Meningitis

Thanks to Dr. Grock for presenting today’s Morning Report!

The Sign Out

45 yo M h/o AIDS (CD4=8, not on HAART) presents with voluminous non-bloody diarrhea x 3 days and near syncope/light-headedness today. No recent travel/antibiotics. He reports trying to drink a lot of fluid, but is a little nauseous, few episodes of vomiting, hasn’t been able to keep up with his losses. No fevers. VS wnl except for mild tachycardia. ECG/CXR nml, Labs off.

Sign Out Plan: F/U CBC/CMP and admit for dehydration/diarrhea/sick.

You see the patient and he complains of headache – gradual onset, occipital, throbbing, associated with midline neck pain, general malaise and has dry MM. CBC significant for WBC=1, CMP unremarkable except for low albumin.

You admit the patient…What are you missing?

AIDS patients have little to no immune system function.
They can be floridly septic/have terrible meningitis and not develop a fever.
Here, WBC and HR = SIRSs criteria.
Non-muscular, midline neck stiffness in AIDS patient = meningitis work-up.

To diagnose

Need prior CT Head noncon/coags, ?CTH w/contras (if neuro def or if CTH w/ lesions).
If CNS lesions WITH mass effect think Toxo, primary CNS lymphoma, brain abscess (from near anything)
If CNS lesions WITHOUT mass effect think Progressive Multifocal Leukoencephalopathy, HIV encephalopathy, CMV

LP results:

Opening pressure=45. Why is this important?
Tube 1: 3 wbc, 2 rbc. Tube 4: 1 wbc, 0 rbc

What do you do with this? (A little help: gram stain returns with yeast)

Diagnosis: Cryptococcal Meningitis

“uniformly fatal within approximately 2 weeks if untreated”
Commonly presents with F/HA/photophobia/N/V/coma
CSF WBC usually <20, glucose/protein nml, crypto ag CSF and serum >90%/99% sens

Treatment

Amphotericin B (use lipid formulation if CKD/AKI) and flucytosine (vs fluconazole)
Ampho + either flucytosine/fluconazole better than ampho alone (faster CSF sterilization and decreased mortality).
Some data that ampho +flucytosine better at csf sterilization than ampho/fluconazole.
NEJM paper: 299 patients, decreased mortality in ampho + flucytosine arm (p = 0.08 @ day 14, p = 0.04 @ day 79) with NNT 7 (according to a website calculator)
Serial LP’s if OP >250
HAART therapy? (IRIS)
- NEJM paper:
  - 117 randomized crypto meningitis (stopped early)
  - Increased Mortality with starting ART < 2wks vs 5wks.
  - Early ART worse in pt’s with wbc<5 in csf.
- Cochrane “This systematic review shows that there is insufficient evidence in support of either early or late initiation of ART. For the moment, because of the high risk of immune reconstitution syndrome in patients with cryptococcal meningitis, we recommend that ART initiation should be delayed until there is evidence of a sustained clinical response to antifungal therapy. However, large studies with appropriate comparison groups, and adequate follow-up are warranted to provide the evidence base for effective decision making.”
Maintenance therapy with fluconazole

References:

Principles of Critical Care, 3^rd ed, chapter 48

Njei B¹, Kongnyuy EJ, Kumar S, Okwen MP, Sankar MJ, Mbuagbaw L.Optimal timing for antiretroviral therapy initiation in patients with HIV infection and concurrent cryptococcal meningitis. Cochrane Database Syst Rev. 2013 Feb 28;2:CD009012. doi: 10.1002/14651858.CD009012.pub2.

David R. Boulware, M.D. et al. Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis N Engl J Med 2014; 370:2487-2498. June 26, 2014DOI: 10.1056/NEJMoa1312884

Jeremy N. Day, M.D., Ph.D. et al. Combination Antifungal Therapy for Cryptococcal Meningitis N Engl J Med 2013; 368:1291-1302April 4, 2013DOI: 10.1056/NEJMoa1110404

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