This handout is for cryptococcal meningitis (hiv-associated and non-hiv). Your care team identified this based on: subacute headache + fever in hiv / immunocompromised host (1-2 wk evolution) (who 2022; idsa 2010 perfect).
Other reasons your team may use this plan: ams over days-weeks in cd4 < 100 or transplant recipient (who 2022; dhhs 2024 oi); visual obscurations / diplopia / papilledema / cn vi palsy — elevated icp phenotype (graybill cid 2000 pmid 10619732); serum crag lfa positive in cd4 < 100 — reflex lp (who 2022; dhhs 2024 oi).
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| liposomal amphotericin B | AMBITION: 10 mg/kg IV × 1 dose (single-dose induction). Alternative 2-wk induction: 3-4 mg/kg IV daily × 14 d. | IV | single dose (AMBITION) OR daily × 14 d | AMBITION Jarvis NEJM 2022 PMID 35320642 — single-dose L-AmB + flucytosine + fluconazole non-inferior to 7-d L-AmB regimen; 10-wk mortality 24.8% vs 28.7%; less nephrotoxicity / anaemia. Preferred where flucytosine available (WHO 2022 Strong recommendation). |
| amphotericin B deoxycholate | 0.7-1 mg/kg IV daily × 14 d (combined with flucytosine) | IV | daily × 14 d | IDSA 2010 Perfect — historical standard; more nephrotoxic + infusion reactions; preferred only when L-AmB unavailable. Pre-medicate acetaminophen + meperidine for chills. Day NEJM 2013 PMID 23550668 demonstrated AmB + flucytosine combination improves survival vs AmB monotherapy (HR 0.61 at 70 d). |
| flucytosine | 100 mg/kg/day PO divided q6h × 14 d (AMBITION + IDSA induction) | PO | q6h × 14 d | IDSA 2010 Perfect + AMBITION Jarvis NEJM 2022 + ACTA Molloy NEJM 2018 — synergistic with polyene; reduces relapse + improves CSF sterilisation. TDM target peak 30-80 µg/mL (toxicity > 100 → bone marrow suppression). Renal-adjust per CrCl. |
| fluconazole | Induction (AMBITION + ACTA): 1200 mg PO daily × 14 d. Consolidation: 800 mg PO daily × 8 wk. Maintenance / secondary prophylaxis: 200 mg PO daily. | PO | daily | AMBITION Jarvis NEJM 2022 PMID 35320642 + ACTA Molloy NEJM 2018 PMID 29539274 — 1200 mg/d component of high-dose oral / single-dose-AmB regimens. Consolidation 800 mg × 8 wk per IDSA 2010 Perfect. Maintenance 200 mg/d until immune recovery (CD4 > 200 × 12 mo on ART) per WHO 2022. |
| voriconazole | 6 mg/kg IV q12h × 2 doses load then 4 mg/kg q12h; TDM trough 2-5 µg/mL for CNS | IV/PO | q12h | IDSA 2010 Perfect — rescue option for refractory / azole-resistant disease; CNS-penetrating with TDM 2-5 µg/mL trough target. Limited large-RCT data in cryptococcal-specific use. |
| isavuconazonium | 200 mg IV/PO q8h × 6 doses load then 200 mg daily | IV/PO | daily after load | No prospective RCT for cryptococcal meningitis; salvage option per IDSA 2010 + ECIL series; fewer DDIs than voriconazole; no QTc prolongation. |
| acetazolamide | NOT recommended for cryptococcal raised ICP | n/a | n/a | IDSA 2010 Perfect + WHO 2022 — acetazolamide, mannitol, hypertonic saline, and corticosteroids NOT effective for cryptococcal raised ICP and may worsen outcomes (Newton Lancet 2002 reported harm with acetazolamide; CRYPTODEX Beardsley NEJM 2016 showed worse outcomes with adjunctive dexamethasone). Therapeutic LP is the evidence-based intervention. |
| dexamethasone | NOT recommended for routine cryptococcal meningitis; consider only for severe IRIS | IV/PO | per IRIS protocol if used | CRYPTODEX Beardsley NEJM 2016 demonstrated harm (higher 6-mo mortality + more disability + adverse events) with adjunctive dexamethasone in induction; therefore NOT used routinely. Reserved for documented severe cryptococcal IRIS with clinical decompensation after ART initiation, per DHHS 2024 OI; preferred initial step is NSAIDs ± continued antifungals while continuing ART. |
Plan: Cryptococcal meningitis induction → consolidation → maintenance ladder (WHO 2022; IDSA 2010 Perfect; AMBITION 2022; ACTA 2018)
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Outpatient ID + HIV / transplant clinic q1-2 wk during consolidation, q monthly during maintenance; serial neurologic + visual + audiologic exam; ART initiation at 4-6 wk if HIV (COAT NEJM 2014); discontinue maintenance fluconazole when CD4 > 200 × 12 mo + VL suppressed on ART; vaccinations per ACIP; counsel C. gattii / pigeon-droppings exposure avoidance; relapse risk highest in first 6 mo — re-LP if clinical change (WHO 2022; IDSA 2010 Perfect; DHHS 2024 OI)
Guideline: WHO 2022 Guidelines for diagnosing, preventing and managing cryptococcal disease + IDSA 2010 (Perfect) Clinical Practice Guidelines for the Management of Cryptococcal Disease + DHHS / CDC / IDSA OI Guidelines (clinicalinfo.hiv.gov 2024 web edition) — anchored by AMBITION 2022, ACTA 2018, COAT 2014, Day 2013, and Graybill 2000 pivotal trials