Anti fungal

Mainly caused by :

-Surgery
-Cancer
-HIV
-Transplant bone marrow
-Broad spectrum antibiotic
Mainly caused by :

-Surgery
-Cancer
-HIV
-Transplant bone marrow
-Broad spectrum antibiotic
Amphotericin
 Produced by : Streptomyces nodosus
 Amphoteric polyene (many double bound) macrolide (large lactone ring, 12/more
atoms)

 Limited usage by renal toxicity => packaged in lipid associated delivery system
• Poorly absorbed
• 90% bound by protein
• T ½ 15 days, not affected by renal or hepatic failure
• Only 2-3% distributed on cerebral fluid => intrathecal needed on fungal meningitis
Mechanism of action :

Resisten :
Ergosterol
binding
impaired,
Modifyed sterol
target molecule
 Usage :
• Candida albicans and Cryptococcus
neoformans;
• endemic mikosis: Histoplasma
capsulatum, Blastomyces dermatitidis,
ESO :
and Coccidioides immitis;
• the pathogenic molds : Aspergillus
1. Infusion related (fever,
fumigatus , mucormycosis.
• Resistance : Candida lusitaniae and chills, muscle spasms, vomiting, headache, and
hypotension)
Pseudallescheria boydii
2. Cumulative toxicity
• Dosage = 0,5-1 mg/kg/d for systemical •Renal damage (azotemia, may need dialysis)
fungal disease, bcz prolonged administration >4g cumulative
• Mycotic corneal ulcer => topical drop = dosage
subconjunctival injection manifest : renal tubular acidosis. Severe
• Fungal arthritis => local injection potas + mg wasting => + loading NaCl
• Candiduria = irrigation bladder •Liver function (anemia, ↓ EPO)
•Intrathecal (seizure, arachnoiditis)
 Flucytosine (5-FC)
 Found 1957 on antineoplasma agent
 Water soluble
 Narrow spectrum
 Only on north America (oral formulation)

USAGE
•100 MG/KF/D
•>90% absorbed
•Peak serum reached at 1-2 h (toxicity, raised peak on HIV and renal impairement
patient => maintain 50-100 mcg/ml)
•Poor protein bound, distributed widely on body fluid
•Eliminated by glomerular filtration T1/2 = 3-4 h
 Usage :
Mechanism of action : •Sinergis with amphotericin B in vitro or in vivo proved
•Monotherapy for UTI fluconazole resistance
•For cryptococcal meningitis => + amphotericin B
•For chromoblastomycosis => + itraconazole
•restricted to C neoformans, some Candida sp, and the dematiaceous
molds that cause
chromoblastomycosis.

ESO :
•Toxic 5-FU
•Bone marrow toxicity, anemia, leukopenia, trombositopenia

Human cells unable to convert

selective toxicity to the fungal

Resistance :

Altered metabolism of flucytosine => developed rapid on

monotherapy
Azoles 5 membered ring
 Usage :
•Candida, C neoformans, the endemic mycoses
Mechanism of action : (blastomycosis, coccidioidomycosis, histoplasmosis), the
dermatophytes, and, in the case of itraconazole, posaconazole,
isavuconazole, and voriconazole, even Aspergillus infections +
amphotericin-resistan organisms such as P boydii.

ESO :
•GIT Upset
•Abnormalities on hepatic enzymes

IMIDAZOL : lesser degree of selectivity with CYP450 human

Interaction ↑, adverse effect ↑

 Ketoconazole :

•Inhibit CYP450
mammalian
•Not used in USA

Fluconazole Itraconazol
voriconazole •good cerebrospinal
penetration •400 mg/d
•100-400 mg/d •Oral BA ↑ •BA >90%
•Increased absorb w/ food •Interaction < itra < keto •Interaction w/cyclosporine, HmgCoAreductase,
•Reduced BA w/ rifampicin •100 -800 mg/d tacrolimus (inhibisi cyp3A4)
•1st choice of dimorphic •IC usage = amphotericin B •ESO : rash, hepatic enzyme, visual disturbance ,
fungi Histoplasma, for candiuria resolve 30’ (IV only)
Blastomyces, and •Fpr cryptococcal •Tx : candida sp (itraconazole)
Sporothrix meningitis, mucocutaneous •Aspergilosis
•For dermatophytosis candidiasis •Environtmentl mold
andonycomycosis •Infection on bone marrow •1-5 mcg/ml
transpl / AIDS
 Cont’d

Isavuconazole
pocasonazole
•Liquid oral 800 mg/d, q 12/q6 h •Preparat : isovuconazolesulfat (newest triazol)
•Absorbed better with food •Strong interaction with CYP34A inhibitor
•Tx : Serious local infection,
(ritonavir) inducer (rifampin) 2-day loading dose
aspergillus, candida,bone marrow
transplant, profilaks for leukemia
of 372 mg administered every 8 hours,
chemotherapy isavuconazonium sulfate is given as a single
•Interaction : tacrolimus, 372-mg daily dose
cyslosporine
 Echinocandin
 Cyclic peptides linked to fatty acid
 Tx : candida + aspergillus sp
 Dosage : IV load 70 mg, followed 50 mg
 Anidafulangin T1/2 = 24-48 h, for esofag candidiasis, candidemia,
 Caspofungin for mucocutaneous infection
 Micafungin, ↑ liver enzyme
 ESO : well tolerated, hypersensitivity, minor GIT Upset,
Mechanism of action :
Oral systemics for mucocutan

Terbinafine
-Fungicidal effect => interfere
ergosterol synthesis
-250 mg/d 12 weeks,
-Onikomikosis, efikasi >
griseofulvin/itranakonazol
Topical

NISTATIN

-Too toxic for systemic

delivery
-Tx : candida sp Topical azole
-Local infection :
oropharingeal, vaginal, -Clotrimazol
intertrigo -miconazol