Dr.Tieman antifungal agents - 8 Flashcards
Risk factors for invasive candidiasis
Prolonged stay in ICU
Central venous catheters
prolonged therapy with broad spectrum antibacterial agents
receipt of parenteral nutrition
recent surgery
hemodialysis
diabetes mellitus
Aspergillus
Mold in the environment
pulmonary system is most common infection
Very difficult to treat
Endemic fungi
Causes disseminated disease via pulmonary infection
common
- histoplasma capsulatum
- blastomyces species
Cryptococcus neoformans
encapsulated yeast that affects CNS
Amphotericin B
Binds to ergosterol and gets inserted into the funcal membrane and leads to leakage of cell and death
1st line in:
Cryptococcus
blastomyces
histoplasma
Mucor
3 formulations
Deoxycholate - 0.5-1 mg/kg/day
Liposomal: 3-5mg/kg daily
Lipid complex: 5mg/kg
AE:
Nephrotoxicity: dose dependent and can increase Scr and BUN (prevention: use normal saline 30 minutes before and after AMB) - EXAM Q
Electrolyte abnormalities: Hypokalemia and hypomagnesemia- EXAM Q
Flucytosine
Same vibe as 5-Fu but works in the fungal cells
Penetrates CSF
Dosing: 25mg/kg/dose PO Q6H
*main use is combo therapy with AmphoB for Cryptococcal meningitis
AE:
Hematologic: bone marrow supression, Monitor CBC, platelets, Scr, BUN
GI upset
Ketoconazole (Nizoral)
Metabolized by the liver
AE:
Hepatotoxicity, endocrine
Lots of drug interactions
Fluconazole (Diflucan)
Dose reduced in renal insufficiency
first line in invasive candidiasis
if C. Albicans: 800mg loading dose, then 400mg daily
if C. glabrata: 800mg daily (loading dose 1200-1600mg)
AE: QTC prolongation, HA, nausea, anorexia, adrenal insufficiency, elevation of hepatic transaminases
First line in:
Candida albicans
Candida Parapsilosis
Candida Tropicalis
Candida lusitaniae
Coccidioides
Itraconazole (sporanox)
Metabolized by CYP3A4 - lots of drug interactions
- oral solution better to take without food but capsules better with food
1st line:
Histoplasmosis: 200mg PO TID x 3 days, then 200mg PO BID
Blastomycosis: 200mg PO TID x 3 days, then 200mg PO BID
SE:
Hepatotoxicity, QTC prolongation
CONTRAINDICATED IN CONGESTIVE HEART FAILURE - EXAM Q
Posaconazole (noxafil)
Decreased absorption with PPIs
IV formulation - AVOID if CRCL <50ml/min
SE: QTC prolongation, N/V, abdominal pain, diarrhea, hypokalemia
Voriconazole (Vfend)
AVOID IV if CLCR <50ml/min
Clinical use
Invasive aspergillosis - FIRST LINE
- loading dose: IV: 6mg/kg IV q12hr for first 24 hours
Maintenance dose
- IV 4mg/kg q 12 hr
- oral: 200mg q12h
Drug interactions CYP3A4, CYP2C9, CYP2C19
SE:
-Visual disturbances –> blurred vision, color changes, photophobia, photopsia, hallucinations - EXAM Q
- elevated liver function test
- QTC prolongation
- Phototoxicity skin reactions
- Diffuse, painful periostitis
Isavuconazole SE
SE:
DOES NOT cause QTC prolongation (Can actually shorten it)
HA
N/V/D
increased LFTS
- least likely to have drug interactions of the azoles
Echinocandins
First line tx for
- C. Glabrata
- C. Krusei
- C. Lusitaniae
- C. Auris
Caspofungin AE
Histamine mediated symptoms, fever, phlebitis at infusion site, N/V, headache
- Not commonly used due to side effect profile
Micafungin (Mycamine)
Give IV
No dose adjustment for renal dysfunction
Clinical use
- Candidemia: 100mg Daily
AE:
Hyperbilirubinemia, Nausea, diarrhea, eosinophilia, rash, pruritus, urticarial
Ibrexafungerp Clinical use
Vulvovaginal candidiasis
- 300mg twice a day for one day
recurrent VVC
- 1 day monthly for 6 months significantly reduced VVC reccurence
CONTRAINDICATED IN PREGNANCY
Oropharyngeal and Esophageal candidiasis
risk factors local and systemic
Local
- Inhaled steroids
- Dentures
- Xerostomia due to drugs
- smoking
- disruption of oral mucosa
Systemic
- drugs
- neonates and elderly
- HIV/AIDs
- diabetes
- malignancies
- nutritional deficiencies
Treatment orapharyngeal candidiasis
Treat for 7-14 days
topical therapy for mild
Nystatin 5ml swish and swallow QID
Systemic therapy for: refractory OPC, pts who cannot tolerate topical, patients with mild to severe, patients with HIV, pts at high risk for disseminated systemic disease (neutropenia)
systemic options
- Fluconazole 100-200mg daily
Treatment esophageal candidiasis
Treat for 14-21 days
systemic therapy always required
- fluconazole 200-400mg PO/IV daily
Vulvovaginal candidiasis treatment
Uncomplicated - sporadic infection that is susceptible to all forms of antifungal therapy regardless of treatment durations
complicated - recurrent VVC, severe disease, non-cadida albicans infection, host factors (immunosuppression, pregnancy)
Topical prescription options
- Nystatin 1 tablet x 14 days
oral script
- fluconazole 150mg tablets, 1 tablet PO x 1 day
