This handout is for endemic mycoses (histoplasmosis / coccidioidomycosis / blastomycosis / paracoccidioidomycosis). Your care team identified this based on: subacute pneumonia / cap-mimic with ohio-mississippi / southwest / great-lakes / latin-american exposure (idsa histo 2007 pmid 17806045; idsa cocci 2016 pmid 27470238; idsa blasto 2008 pmid 18462107).
Other reasons your team may use this plan: fever + weight loss + hepatosplenomegaly + pancytopenia in immunocompromised host — disseminated mycosis (idsa histo 2007 pmid 17806045); mucocutaneous oral / nasopharyngeal / verrucous skin lesions in latin-american or se-us host — paracocci or blasto (shikanai-yasuda 2017 pmid 28746570; idsa blasto 2008 pmid 18462107); subacute basilar meningitis in sw-us / mexico traveler — coccidioidal meningitis (idsa cocci 2016 pmid 27470238).
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 |
|---|---|---|---|---|
| itraconazole | Mild-moderate (histo / blasto / paracocci): 200 mg PO TID × 3 d (load) → 200 mg PO BID × 6-12 mo. Severe step-down (after L-AmB): 200 mg PO BID × ≥ 12 mo. Cocci (alternative to fluconazole): 200 mg PO BID-TID × 3-6 mo. | PO | BID-TID | IDSA histo 2007 PMID 17806045 + IDSA blasto 2008 PMID 18462107 + Shikanai-Yasuda 2017 PMID 28746570 — itraconazole is first-line for mild-moderate histo and blasto and paracocci, and is step-down maintenance after L-AmB for severe disease. TDM trough > 1 µg/mL HPLC (> 2 µg/mL bioassay). Oral solution > capsule absorption; food / acid-pH-dependent capsule absorption; avoid PPIs with capsules. Rifampin is absolute contraindication (CYP3A4 induction destroys levels). Capsule-to-oral-solution-to-IV switching requires re-targeting TDM. |
| amphotericin B liposomal | Severe / disseminated: 3-5 mg/kg IV daily × 1-2 wk → step-down to itraconazole or fluconazole. CNS histoplasmosis: 5 mg/kg IV daily × 4-6 wk → itraconazole BID-TID × ≥ 12 mo. Pregnancy preferred antifungal. | IV | daily | Johnson Ann Intern Med 2002 PMID 12118965 RCT — L-AmB superior to AmB-deoxycholate for moderate-severe disseminated histo in AIDS (clinical success 88% vs 64%; less nephrotoxicity 9% vs 37%; less infusion reactions 25% vs 63%; mortality 1/51 vs 3/22). IDSA histo 2007 PMID 17806045 + IDSA blasto 2008 PMID 18462107 — L-AmB induction for severe / disseminated / CNS. Pregnancy preferred per IDSA cocci 2016 PMID 27470238. |
| amphotericin B | AmB deoxycholate 0.7-1 mg/kg IV daily × 1-2 wk + pre-medicate acetaminophen + diphenhydramine + meperidine + IVF. Only when L-AmB unavailable. | IV | daily | Johnson Ann Intern Med 2002 PMID 12118965 showed inferior to L-AmB (more nephrotoxicity, infusion reactions, mortality); reserved for L-AmB-unavailable settings per IDSA histo 2007 + IDSA blasto 2008. |
| fluconazole | Cocci mild-moderate pulmonary: 400-800 mg PO daily × 3-6 mo. Cocci severe / disseminated: 400-1200 mg PO daily × 6-12 mo. Cocci meningitis: 400-1200 mg PO daily LIFELONG (no taper). Histo / blasto: only when itraconazole intolerant — 800 mg PO daily. | PO | daily | IDSA cocci 2016 PMID 27470238 — fluconazole first-line for cocci across severity tiers; cocci meningitis requires LIFELONG fluconazole 400-1200 mg/d (relapse common on withdrawal per Dewsnup et al CID 1996). Better CNS penetration than itraconazole. QTc + DDI screen (warfarin, tacrolimus, cyclosporine, sulfonylureas, statins, phenytoin, rifampin). |
| voriconazole | Load 6 mg/kg IV q12h × 2 doses → 4 mg/kg IV q12h or 200-300 mg PO q12h. TDM trough 1-5.5 µg/mL. | IV/PO | q12h | IDSA blasto 2008 PMID 18462107 + IDSA cocci 2016 PMID 27470238 — voriconazole rescue for CNS blasto and refractory cocci. CYP2C19 metabolism + TDM required (trough 1-5.5 µg/mL); QTc / visual disturbance / skin photo-toxicity / SCC-risk on prolonged therapy. |
| posaconazole | Delayed-release tablet 300 mg PO BID × 1 d → 300 mg PO daily; suspension 200 mg PO TID with food; IV 300 mg q12h × 2 → 300 mg daily. TDM trough > 1 µg/mL. | PO/IV | daily-TID | IDSA cocci 2016 PMID 27470238 + Restrepo case series — posaconazole salvage for refractory disseminated endemic mycosis. Delayed-release tablet preferred over suspension (better bioavailability + less food dependence). DDI profile mirrors itraconazole (CYP3A4). |
| isavuconazonium | Load 200 mg IV/PO q8h × 6 doses → 200 mg daily. | IV/PO | daily after load | IDSA cocci 2016 + emerging case-series support; fewer DDIs than voriconazole; no QTc prolongation (actually shortens QT); no cyclodextrin vehicle. Limited prospective endemic-mycosis RCT data. |
| terbinafine | 250-500 mg PO daily, often combined with itraconazole for refractory cutaneous / mucocutaneous paracocci or chromoblastomycosis-overlap | PO | daily | Shikanai-Yasuda 2017 PMID 28746570 — terbinafine adjunct considered in select refractory paracocci / chromoblastomycosis-overlap; not first-line for systemic endemic mycoses. |
| sulfamethoxazole / trimethoprim (TMP-SMX) | 160 mg / 800 mg PO BID × 12-24 mo (paracocci alternative when itraconazole unavailable) | PO | BID | Shikanai-Yasuda 2017 PMID 28746570 — TMP-SMX is the historical resource-limited alternative for paracocci; longer duration (12-24 mo) than itraconazole; monitor LFTs + CBC + creatinine + sulfa allergy. |
Plan: Endemic mycoses induction → maintenance ladder by organism × severity × host (IDSA histo 2007; IDSA cocci 2016; IDSA blasto 2008; Shikanai-Yasuda 2017)
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
ID outpatient q1-3 mo through 6-12 mo of therapy + lifelong for cocci meningitis; HIV / transplant clinic concurrent; vaccinations per ACIP after immune-recovery; exposure-avoidance counselling (no spelunking / dusty soil disruption in endemic areas while immunocompromised); fertility / pregnancy planning if azole maintenance ongoing; mental-health screening for post-critical-illness sequelae; pulmonary rehab for fibrotic / cavitary sequelae; relapse vigilance — return of fever / cough / weight loss / mucocutaneous lesion → re-evaluation (IDSA histo 2007; IDSA cocci 2016; IDSA blasto 2008; Shikanai-Yasuda 2017).
Guideline: IDSA histoplasmosis 2007 (Wheat et al CID, PMID 17806045) + IDSA coccidioidomycosis 2016 (Galgiani et al CID, PMID 27470238 / executive summary 27559032) + IDSA blastomycosis 2008 (Chapman et al CID, PMID 18462107) + Brazilian consensus paracoccidioidomycosis 2017 (Shikanai-Yasuda et al RSBMT, PMID 28746570) + ATS Clinical Practice Guideline microbiology of pulmonary fungal infections 2019 (Hage et al Am J Respir Crit Care Med, PMID 31469325) + Johnson et al Ann Intern Med 2002 L-AmB pivotal RCT (PMID 12118965)