1 Match the drug to the organism
Aspergillus or Penicillium›Itraconazole (classic first line), voriconazole, posaconazole, or isavuconazole
Mucorales (Mucor, Rhizopus)›Posaconazole or isavuconazole · not itraconazole, not voriconazole
Fusarium›Voriconazole or posaconazole · not isavuconazole
Scedosporium apiospermum›Voriconazole (posaconazole as backup) · not isavuconazole
Dark (dematiaceous) molds›Itraconazole, voriconazole, or posaconazole
Fluconazole›No mold coverage. Yeasts only, do not use it to treat a mold.
2 Spectrum at a glance
✓ covers
~ variable or unreliable
× does not cover
Amphotericin B is the broad-spectrum polyene, and it earns a place here. Reach for it as a nasal spray or rinse for stubborn sinus colonization, or oral (non-absorbed, 250 mg per capsule) for gut fungal overgrowth that nystatin did not settle. IV is reserved for invasive disease. It also covers Candida and other yeasts, and covers the Mucor the azoles miss. Fluconazole is a yeast drug, not a mold drug: Candida (but not glabrata or krusei), Cryptococcus, and Coccidioides. Suspect Candida with recurrent thrush or vaginal yeast, after antibiotics or steroids, in diabetes, or the sugar-craving gut-dysbiosis picture. It rides alongside mold illness but is not the mold.
3 Where it goes, and multiple exposures
Brain / CSF infection›Voriconazole or fluconazole, the two that reach spinal fluid. Itraconazole and posaconazole barely enter CSF.
Sinus / lung›Itraconazole or posaconazole (voriconazole also). They concentrate in respiratory tissue.
Gut colonization›Nystatin for luminal only. Itraconazole when you want mucosal levels plus immune modulation. Oral amphotericin (250 mg caps) when nystatin did not settle it.
Skin / eczema›Itraconazole concentrates in skin. Urinary yeast, fluconazole.
Multiple exposures›Cover the gap, not the overlap. Mucor in the mix needs posa or isavu. Fusarium needs vori. For both, or the broadest single agent, posaconazole.
Itraconazole, more than an antifungal. Beyond Aspergillus and Penicillium, itraconazole carries anti-inflammatory and immune-modulating effects the other azoles largely lack: Hedgehog and VEGFR2 inhibition, T-cell and neutrophil suppression. That is why it is favored in gut-driven, neuroinflammatory, and chronic cases, and in pediatric mold and ASD work it is pulsed (about 5 mg/kg, max 100 mg, every 3 to 4 days then every other day, 4 to 6+ months, LFTs at 6 to 8 weeks then every 2 to 3 months). Its brain benefit is systemic immune modulation, not CSF level, which stays low.
4 QT effect, with the facts
↓ shortensIsavuconazole. Shortens the QTc about 5 msec, more at higher drug levels. The QT-sparing choice. Contraindicated in familial or congenital short QT syndrome.
↑ prolongsVoriconazole. Prolongs QTc, and it rises with higher drug levels, part of why it needs level monitoring.
↑ prolongsPosaconazole. Prolongs QTc, but the effect is small, around 4 percent in a trial. The gentlest of the prolongers.
↑ prolongsItraconazole. Prolongs QTc, and it is also a negative inotrope. The bigger flag is heart failure, not just the QT.
↑ prolongsFluconazole. Prolongs QTc, dose related. Negligible at 150 to 200 mg, a concern at 400 to 800 mg and up, or stacked on other QT drugs or low potassium or magnesium.
5 Before you prescribe
Baseline ECG and electrolytes. Before any QT-prolonging azole, check and correct potassium and magnesium. Mold and CIRS patients often start with dysautonomia and electrolyte wasting.
On QT-prolonging Lyme antibiotics? Azithromycin, clarithromycin, the fluoroquinolones. Isavuconazole offsets rather than stacks, so it is the smart pairing.
Short QT syndrome. Do not use isavuconazole. Its QT shortening becomes the risk.
Heart failure or LV dysfunction. Caution or avoid itraconazole for its negative inotropy, apart from the QT question.
How long to treat. The endpoint is clinical: symptoms improving and the urine mycotoxins dropping and clearing on a retest, once the exposure is gone. There is no firm minimum for mold illness, but useful anchors: antifungal courses usually run 3 to 6 months (itraconazole often 4 to 6+ months), the overall protocol 6 to 12 months, and invasive-disease courses a minimum of 6 to 12 weeks. Retest the urine mycotoxins after a real treatment block, around 3 to 6 months and after exposure is removed, not sooner, or the result just reflects what is still mobilizing.
Context: most spectrum data come from invasive disease. In mold illness the organism is usually Aspergillus or Penicillium colonizing the sinuses or gut, so itraconazole, posaconazole, and isavuconazole all cover the usual case. The Fusarium, Mucor, and Scedosporium distinctions matter mainly when one of those shows up on a culture. For Stachybotrys the issue is the mycotoxin (trichothecenes), so remove the exposure and bind it (cholestyramine, charcoal, clay) rather than reaching for an azole. For Wallemia it is mostly an allergen and hypersensitivity problem, so remove the exposure and settle the immune response. One more on inputs: choosing by organism needs a culture or environmental test (EMMA). A urine mycotoxin panel shows toxins, not species, and never shows Mucor.