Lesson
Recognize a Quiet but Dangerous Meningitis
Profound immune loss can permit a high fungal burden with limited inflammation. The presentation is often subacute and may lack classic meningismus.
- Capsule
- Melanin
- CD4 below 100
- Subacute headache
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Place the organism
Cryptococcus neoformans is an encapsulated yeast found worldwide. Inhaled organisms can disseminate hematogenously, cross into the CNS, and exploit weakened cell-mediated immunity.
Read the timeline
Headache, fever, malaise, nausea, cognition change, visual symptoms, or cranial neuropathy usually evolve over days to weeks. Neck stiffness and focal deficits may be absent.
Respect weak inflammation
A low CSF white-cell response does not guarantee mild disease. Advanced immunosuppression can permit heavy fungal burden, high intracranial pressure, and minimal meningeal signs.
Stabilize threats
Evaluate seizure, papilledema, focal deficit, altered consciousness, and herniation risk. These findings determine imaging and lumbar-puncture safety without delaying definitive care unnecessarily.
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Lesson
Stage Antigenemia Before Choosing Intensity
Cryptococcal antigen identifies infection, while CSF pressure, antigen, culture, and inflammatory data define CNS involvement and treatment intensity.
- Serum CrAg
- CSF CrAg
- Fungal culture
- Opening pressure
- Titer
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Use serum CrAg
Serum lateral-flow CrAg is highly sensitive and helps detect disease in advanced HIV. Record the assay and titer because high-titer antigenemia predicts meningitis and mortality.
Perform a complete LP
When safe, measure opening pressure and obtain CSF CrAg, fungal culture, cell count, glucose, protein, and studies for alternative meningitides. Record pressure in centimeters of water.
Treat high-risk antigenemia
Non-CNS symptoms, extrapulmonary disease, diffuse pulmonary disease, or serum LFA titer at least 1:640 requires meningitis-level treatment even if initial CSF is normal.
Use staged fluconazole only in lower-risk disease
Fully asymptomatic antigenemia with normal CSF and lower titer can use fluconazole 800 to 1,200 mg daily for 2 weeks, then 400 to 800 mg for 10 weeks, then 200 mg daily for a total of 6 months with effective ART.
Do not follow titers as culture
Persistent antigen can remain after viable organisms clear. CSF culture and clinical response, not serial titer alone, determine microbiologic control.
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Lesson
Pair Fungicidal Activity With Exposure Control
Preferred induction combines membrane disruption by liposomal amphotericin B with intracellular nucleic-acid inhibition by flucytosine.
- Ergosterol
- Liposomal amphotericin B
- Flucytosine
- Renal adjustment
- Combination therapy
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Use the preferred regimen
Give liposomal amphotericin B 3 to 4 mg/kg IV daily plus flucytosine 25 mg/kg orally every 6 hours for 2 weeks. Formulations are not interchangeable milligram for milligram.
Understand amphotericin
Binding fungal ergosterol creates membrane pores. Liposomal delivery reduces, but does not eliminate, nephrotoxicity, potassium and magnesium wasting, anemia, and infusion reactions.
Understand flucytosine
Fungal cells convert flucytosine into fluorouracil metabolites that disrupt RNA and DNA synthesis. Monotherapy rapidly selects resistance.
Engineer renal dosing
Flucytosine is renally cleared. Adjust the interval as kidney function declines and use drug levels when available, especially because amphotericin can impair clearance during the same course.
Prevent predictable toxicity
Use saline when appropriate, scheduled electrolyte surveillance and replacement, CBC and liver monitoring, and a plan for infusion reactions. Reduce avoidable nephrotoxins.
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Lesson
Treat Pressure as a Separate Emergency
Antifungal therapy does not rapidly correct CSF outflow obstruction. Therapeutic drainage is an independent survival intervention.
- Opening pressure
- Serial LP
- Closing pressure
- CSF diversion
- Vision
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Drain when indicated
With symptoms of raised pressure or opening pressure at least 25 cm water, remove enough CSF to reduce pressure by about 50 percent or to 20 cm water or less.
Repeat daily when needed
Reassess headache, vision, hearing, cognition, and pressure. Repeat therapeutic LP daily until pressure and symptoms stabilize.
Escalate refractory pressure
Persistent elevation despite repeated LP can require a lumbar drain, ventriculostomy, or shunt with specialist support.
Avoid ineffective substitutes
Acetazolamide, mannitol, and routine corticosteroids do not replace CSF drainage and may cause harm. Use steroids only for another clearly defined indication such as severe IRIS.
Document effect
Record opening and closing pressure, volume removed, symptoms before and after, procedural barriers, and the next scheduled assessment.
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Lesson
Let CSF Sterility Determine the Phase Change
A calendar does not prove fungal clearance. Culture and clinical control decide when induction can safely become consolidation.
- Repeat culture
- Sterility
- Fluconazole 800 mg
- Eight weeks
- Persistent infection
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Reassess at 1 to 2 weeks
Repeat LP and culture when clinically indicated, particularly with high burden, poor response, or pressure concerns. Manage pressure at the same procedure.
Use culture as the microbiologic endpoint
A sterile CSF culture supports transition after adequate induction. CrAg titer does not replace culture for viable-organism clearance.
Consolidate at treatment intensity
Use fluconazole 800 mg daily for at least 8 weeks. Adjust for renal function and monitor liver, QT, and interaction risk.
Extend for persistent culture
Continue or intensify induction when CSF remains culture positive. Provide 8 weeks of consolidation from the date culture is confirmed negative.
Investigate failure
Audit dosing weight, infusion completion, flucytosine access and levels, renal adjustment, interactions, susceptibility, immune status, and intracranial pressure.
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Lesson
Delay ART, Then Restore Durable Host Control
Cryptococcal meningitis is an exception to immediate ART. Stabilizing fungal disease and pressure first reduces fatal inflammatory injury.
- Fluconazole 200 mg
- One year
- ART delay
- IRIS
- CD4 recovery
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Maintain after consolidation
Use fluconazole 200 mg daily for at least 1 year from antifungal initiation. Confirm access and interaction safety across the long course.
Delay ART 4 to 6 weeks
Unlike most opportunistic infections, begin ART 4 to 6 weeks after antifungal therapy starts for CNS disease. Earlier ART increases mortality from CNS IRIS.
Recognize IRIS
Recurrent meningitis symptoms with sterile cultures after ART can represent IRIS. Continue ART and antifungal therapy, manage pressure, and reserve corticosteroids for severe inflammation.
Separate relapse
Positive culture suggests microbiologic relapse or failure rather than IRIS. Reinduce and investigate adherence, interaction, exposure, and resistance.
Stop only after recovery
Stop maintenance after at least 1 year when the patient is asymptomatic, HIV RNA is suppressed, and CD4 is at least 100 cells/mm3. Restart if CD4 falls below 100.
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Lesson
Monitor the Whole Antifungal Sequence
Toxicity changes by phase: amphotericin injures kidney and electrolytes, flucytosine suppresses marrow, and fluconazole adds hepatic, QT, and interaction risk.
- Creatinine
- Potassium
- CBC
- Liver
- QT
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During induction
Monitor creatinine, potassium, magnesium, CBC, liver tests, infusion reactions, volume status, and interacting nephrotoxins frequently. Replace electrolytes proactively.
Protect flucytosine exposure
Renal dysfunction requires interval adjustment. Concentration-related toxicity includes neutropenia, thrombocytopenia, anemia, and liver injury.
During fluconazole phases
Monitor hepatic function, renal dose needs, QT risk, and CYP interactions with ART, anticoagulants, anticonvulsants, immunosuppressants, and other drugs.
Reject class substitution
Echinocandins do not have clinical activity against Cryptococcus. A familiar antifungal class is not an acceptable substitute without organism-specific evidence.
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Lesson
Match Treatment to Site and Burden
Cryptococcosis outside the meninges ranges from low-risk focal lung disease to disseminated infection that deserves CNS-level treatment.
- Pulmonary
- Disseminated
- High titer
- Pregnancy
- CNS staging
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Treat disseminated disease like CNS disease
Non-CNS extrapulmonary disease and diffuse pulmonary cryptococcosis receive the same induction approach as meningitis and require CNS evaluation.
Identify lower-risk pulmonary disease
Mild focal pulmonary infiltrates with negative serum CrAg can use fluconazole 400 mg daily for 6 to 12 months with effective ART, guided by symptom resolution.
Interpret antigenemia by risk
Low-titer, asymptomatic, CSF-negative infection can use staged fluconazole. High titers or systemic symptoms require meningitis-level treatment.
Coordinate pregnancy care
Life-threatening CNS disease generally requires amphotericin-based treatment. Azole and flucytosine decisions require current pregnancy evidence and maternal-fetal, HIV, and infectious-disease expertise.
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Lesson
Build a Three-Phase System With Pressure Control
Cryptococcal meningitis care is not one prescription. It is a coordinated sequence of fungal killing, CSF drainage, culture clearance, consolidation, delayed ART, and maintenance.
- Induction
- Pressure
- Consolidation
- ART
- Maintenance
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Own induction
Confirm exact amphotericin formulation and weight-based flucytosine, daily delivery, renal adjustment, electrolyte replacement, CBC, liver tests, and infusion support.
Own pressure
Record opening and closing pressure, symptoms, drainage volume, daily reassessment, and the escalation pathway for refractory pressure.
Own culture
Track every CSF culture to final result. Positive culture changes induction length and resets the consolidation clock.
Own transitions
Start fluconazole consolidation at the correct dose, delay ART 4 to 6 weeks, then move to maintenance without a medication gap.
Own long-term recovery
Track adherence, interactions, HIV RNA, CD4, symptoms, relapse signals, maintenance duration, stopping criteria, and restart criteria.
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Module test
Check the connections.
Each attempt draws 10 questions from the complete 100 question bank.
Each attempt draws a fresh set and rearranges the answer choices.
References
Current clinical foundation.
Lecture material was synthesized with the following contemporary guidance. Verify local policy and current guidance before applying clinical information.