Microbiology · Year 2 · from Microbiology

Case 1: Cryptococcal Meningitis in HIV

Presentation

A 38-year-old man with HIV (not on antiretroviral therapy, last CD4 count 45 cells/μL) presents with 2 weeks of progressive headache that has become severe over the past 3 days. He also reports neck stiffness, low-grade fever, and mild confusion. He has no photophobia or focal neurologic deficits. Lumbar puncture shows an opening pressure of 42 cm H2O, CSF with 35 WBC/μL (95% lymphocytes), protein 85 mg/dL, and glucose 28 mg/dL. India ink preparation reveals encapsulated yeast organisms. Serum and CSF cryptococcal antigen are both strongly positive at titers >1:1024.

Clinical Image

India ink preparation of cerebrospinal fluid demonstrating encapsulated yeast cells of Cryptococcus neoformans. The capsule appears as a clear halo around the organism against the dark ink background.

Image Source: Lecture image - Cryptococcus diagnosis

Questions

  1. What is the diagnosis, and why is this patient at particular risk?
  1. What is the significance of the markedly elevated opening pressure?
  1. What is the recommended treatment approach for cryptococcal meningitis?
  1. What complications should be anticipated during treatment?

Answers

  1. Diagnosis and risk factors: This is cryptococcal meningitis caused by Cryptococcus neoformans. This patient is at high risk because of AIDS with CD4 count <100 cells/μL. Cryptococcal meningitis is an AIDS-defining illness and occurs almost exclusively in severely immunocompromised patients. C. neoformans is found in soil contaminated with pigeon droppings and is acquired through inhalation. Its polysaccharide capsule is the major virulence factor, inhibiting phagocytosis and allowing CNS invasion.
  1. Significance of elevated opening pressure: The markedly elevated opening pressure (normal <20 cm H2O) is critical for both morbidity and mortality. Elevated intracranial pressure (ICP) is the primary cause of early death in cryptococcal meningitis. The organism's polysaccharide capsule and inflammatory response obstruct CSF outflow. Management requires:
  • Therapeutic lumbar puncture: Remove enough CSF to reduce pressure by 50% or to normalize
  • Daily LPs may be needed until pressure normalizes
  • Ventriculoperitoneal shunt for refractory cases
  • This is often overlooked but is as important as antifungal therapy
  1. Treatment approach: Treatment follows a three-phase strategy:
  • Induction (at least 2 weeks): Liposomal amphotericin B + flucytosine (5-FC) - this combination has demonstrated superior fungicidal activity
  • Consolidation (8 weeks): Fluconazole 400-800 mg daily
  • Maintenance (indefinite until immune reconstitution): Fluconazole 200 mg daily
  • ART initiation: Delay 4-6 weeks after starting antifungal therapy to reduce IRIS risk
  • Maintenance can be discontinued after CD4 >100 cells/μL for >3 months on suppressive ART with undetectable viral load
  1. Anticipated complications:
  • Elevated ICP causing herniation (monitor and treat aggressively)
  • Drug toxicities: Nephrotoxicity and electrolyte abnormalities (amphotericin B), bone marrow suppression (flucytosine), hepatotoxicity (fluconazole)
  • Immune reconstitution inflammatory syndrome (IRIS): Paradoxical worsening after ART initiation as immune system mounts inflammatory response; may present with worsening headache, fever, lymphadenopathy, or new neurologic findings; managed with corticosteroids while continuing both antifungal and ART
  • Relapse: High without maintenance therapy

All cases for this lecture as Markdown