PCOL Antifungals Flashcards
Types of Yeast
Candida - C. albicans, C. glabrata, C. tropicalis, C. krusei
Cryptococcus
Types of Mold
Aspergillus
Mucor
Rhizopus
Types of Dipmorphic Fungi
Histoplasma
Blastomyces
Coccidiodes
Polyenes Drugs
Ampothericin B
Amphotericin B Spectrum of Coverage
Amophotericin B Indications
Reserved for invasive fungal infections (due to toxicities)
First-line for: Mucormycosis infections, Cryptococcus infections, and Histoplasmosis infections
Second-line for Aspergillosis infections (for pts who cannot tolerate voriconazole)
Last-line for Candida infections (safer options with same efficacy)
Amphotericin B Route of Administration
IV only
Amphotericin B ADRs
Infusion-related reactions (can be treatment-limiting, can give pre-medications before, such as APAP, steroids, and diphenhydramine to help)
Nephrotoxicity (most treatment-limiting, sodium loading with NS before each administration)
Electrolyte abnormalities from nephrotoxicity - hypokalemia, hyponatremia, hypomagnesemia
Amphotericin B DDIs
Avoid use with concomitant nephrotoxic agents (vanco, aminoglycosides, colistin)
Lipid Amphotericin B Formulations Drugs
Abelcet and Ambisome
Lipid Amphotericin B Advantages
Lower risk of infusion-related reactions and nephrotoxicity, but still some risk
Allow us to give higher doses of Amphotericin
When is Ambisome preferred?
For CNS infections
Triazole Drugs
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Isavuconazole
Fluconazole Spectrum of Activity
Fluconazole Indications
Infections due to yeasts: Candida (except krusei) and Cryptococcal
Infections due to Cocci (DOC for most Cocci infections)
Fluconazole Route of Administration
PO and IV
Fluconazole Dose Adjustments for Organ Dysfunction
Renal dose adjustment required if CrCl < 50 (decrease dose by 50%)
ONLY azole that requires renal dose adjustment
Fluconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
Fluconazole DDIs
CYP2C19 - warfarin, phenytoin
Avoid concomitant QT prolonging meds
Itraconazole Spectrum of Activity
Itraconazole Indications
Histoplasmosis infections (outside of CNS)
Alternative for other invasive infections for invasive organisms
Onychomycosis (fungal nail infection)
Itraconazole Route of Administration
PO only (capsules and oral solution)
Can you switch itraconazole formulations in the middle of therapy?
No, they are not interchangeable because they have different bioavailabilities
Which formulation of itraconazole is preferred?
Oral solution because of better absorption
Does itraconazole require dose adjustments for organ dysfunction?
No
Itraconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
Itraconazole BBWs
DDI with other CYP3A4 drugs (cisapride, pimozide, methadone, quinidine) → QT prolongation and ventricular tachyarrhythmias
Can cause exacerbation of CHF (AVOID in pts with history of HF)
Itraconazole Counseling Points
Capsules and tablets should be taken with a full meal for best absorption and should AVOID concomitant administration with antacid, PPI, or H2RA
Oral suspension should be taken on an empty stomach for better absorption
Voriconazole Spectrum of Activity
Voriconazole Indications
First line for Aspergillosis
Second line for yeast infections or dimorphic infections
Voriconazole Route of Administration
PO and IV
Voriconazole Therapeutic Drug Monitoring
Should do therapeutic drug monitoring for Voriconazole
Target trough range: 2-5.5 micrograms/mL
Timing of blood draws:
- If loading dose is given: 30 mins prior to 4th dose
- If loading dose is not given: 30 mins prior to 10th or 11th dose (day 5-6)
Voriconazole Dose Adjustments
Hepatic dose adjustment for Child Pugh A and B
No renal dose adjustment needed, but PO recommended in CrCl < 50 (IV formulation contains cyclodextrin)
Voriconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
Visual disturbances
Photophobia
Hallucinations
Cutaneous malignancy (with long-term use)
Voriconazole DDIs
Contraindicated with rifampin, carbamazepine, long-acting barbiturates, and sirolimus
Posaconazole Spectrum of Activity
Posaconazole Indications
Alternative for Candida, mold, and dimorphic fungi
Prophylaxis to prevent invasive fungal infection in neutropenic host
Posaconazole Route of Administration
PO (tablets and oral suspension) and IV
Which posaconazole oral formulation is preferred?
Delayed release tablets preferred over oral suspension
Posaconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
Posaconazole Dose Adjustments for Organ Dysfunction
No dose adjustment for renal or hepatic dysfunction
PO formulation recommended in pts with CrCl < 50 (IV formulation contains cyclodextrin)
Posaconazole Patient Counseling
Oral suspension - take within 20 mins of full meal or liquid nutritional supplement or acidic carbonated beverage
Delayed release tablet - take with food to minimize gastric irritation
Isuvuconazole Spectrum of Activity
Isuvuconazole Indications
Alternative for invasive Aspergillosis or Mucormycosis infections
Should NOT be used for invasive candidiasis
Isuvuconazole Route of Administration
PO or IV
Isuvuconazole Dose Adjustment for Organ Dysfunction
Dose adjustment not needed in renal or hepatic dysfunctioni
Use with caution in Child Pugh Class. C
Isuvuconazole ADRs
Hepatotoxicity (class effect)
QT shortening - use caution in familial short QT syndrome
Isuvuconazole DDIs
Contraindicated with Rifampin and Lopinavir/ritonavir
Echinocandins Drugs
Caspofungin
Micafungin
Anidulafungin
Echinocandins Spectrum of Activity
Echinocandins Indications
Candidemia (Candida bloodstream infection)
Invasive Candidiasis (NOT CNS infections)
Alternative therapy for Aspergillosis
Echinocandins Dose Adjustment for Organ Dysfunction
Do not require dose adjustment for renal or hepatic dysfunction
Good alternative to azoles in pts with hepatic dysfunction
Echinocandins Route of Administration
IV only
Caspofungin DDIs
Cyclosporine, tacrolimus, rifampin, phenytoin
Micafungin DDIs
Sirolimus, nifedipine
Anidulafungin DDIs
Cyclosporine
Echinocandins ADRs
Well-tolerate (like to use them in critically ill pts in the ICU, no nephrotoxicity or infusion-related reactions like Amphotericin and no hepatotoxicity or QT prolongation like azoles)
Transaminitis - MUCH lesser extent than azoles
Thrombophlebitis (caspofungin)
Infusion-related reaction (anidulafungin) - VERY mild compared to Amphotericin
Flucytosine Spectrum of Activity
Flucytosine Indications
In combination with amphotericin B or fluconazole for Candida or Cryptococcus infections (specifically meningitis)
Should NOT be used as monotherapy - rapid development of resistance
Flucytosine Route of Administration
PO only
Flucytosine Dose Adjustment for Organ Dysfunction
Dose adjustment required for CrCl < 40
Caution with concomitant hepatotoxic agents
Flucytosine ADRs
Bone marrow suppression (can be treatment limiting)
Hepatotoxicity (not usually treatment limiting)
Nystatin Indications
Mild oral candidiasis (thrush)
Nystatin Route of Administration
Oral suspension
Nystatin Patient Counseling
Wait 20-30 min to eat before taking Nystatin; brush teeth at least 30 min after taking because it contains sugar
Terbinafine Indications
Onychomycosis (fungal nail infection)
Tinea infections that do not respond to topical therapy or extensive infection
Terbinafine Route of Administration
PO
Terbinafine Contraindication
Contraindicated in chronic or active liver disease
Terbinafine ADRs
Hepatotoxicity - main toxicity we worry about
Headache - most common
Taste disturbance
May cause decrease in lymphocyte or neutrophil count
Terbinafine Monitoring Parameters
AST/ALT
Taste disturbance
CBC if duration > 6 months and history of preexisting immunosuppression
Griseofulvin Indications
Onychomycosis (fungal nail infection)
Tinea infections that do not respond to topical therapy or extensive infection
Griseofulvin Route of Administration
PO (oral suspension and tablets)
Griseofulvin Contraindications
Chronic or active liver disease
Pregnancy
Porphyria
Males should avoid fathering a child for 6 months after taking
Griseofulvin Patient Counseling
Take with a fatty meal to increase absorption and decrease GI upset
Avoid alcohol - can cause disulfiram reaction
Antifungals Safe in Pregnancy
Amphotericin B - DOC for invasive fungal infection in pregnancy
Topical Azoles - safe for superficial infections in pregnancy
Nystatin - safe for thrush in pregnancy
Topical Terbinafine - use only if treatment cannot be delayed until after pregnancy
Antifungals NOT Safe in Pregnancy
Avoid systemic azoles in pregnancy
Caution use of echinocandins in pregnancy
Flucytosine contraindicated in pregnancy
Systemic terbinafine contraindicated in pregnancy
Griseofulvin contraindicated in pregnancy
Non-invasive Candidiasis
Thrush - mouth or esophagus
Vulvovaginal candidiasis
Signs and symptoms of oral thrush
Curdlike white patches over tongue - “cottony mouth”
Risk factors for oral thrush
Use of inhaled steroids
Denture use
Xerostomia (dry mouth)
Malignancy
AIDS
Signs and symptoms of esphageal thrush
White plaque in esophagus
Painful swallowing, feeling of obstruction when swallowing
Substernal chest pain
N/V
Risk factors for esophageal thrush
Malignancy
AIDS
Long-term Omeprazole use
Treatment of mild oral thrush
Clotrimazole troches
Miconazole mucoadhesive buccal tablets
Nystatin oral suspension
Treatment of moderate to severe oral thrush
Fluconazole PO (systemic)
Treatment Duration for Oral Thrush
7-14 days
What to do if refractory to fluconazole in treatment of oral thrush?
Itraconazole oral solution or Posaconazole oral suspension
Treatment of esophageal thrush
Systemic therapy always needed
Preferred: Fluconazole PO or IV
Alternative: Echinocandin IV
Treatment duration of esophageal thrush
14-21 days
What to do if refractory to fluconazole in treatment of esophageal thrush?
Itraconazole oral solution
Posaconazole oral suspension
Voriconazole
Common Pathogen Causing Vulvovaginal Candidiasis
Candida albicans
Risk Factors for Developing Vulvovaginal Candidiasis
Diabetes
Antibiotic therapy
Pregnancy
Some birth control pills
Signs of Vulvovaginal Candidiasis
Thick, curdy, odorless vaginal discharge
Uncomplicated Vulvovaginal Candidiasis
Sporadic or infrequent VVC AND
Mild-moderate VVC AND
Likely to be C. albicans AND
Non-immunocompromised
Complicated Vulvovaginal Candidiasis
Any one of the following:
Recurrent VVC (at least 4 times in 1 year)
Severe VVC (extensive vulvar erythema, edema, excoriation, fissure formation)
Non-albicans candidiasis
Women with DM, immunocompromising conditions (HIV), debilitation, or immunosuppressive therapy (steroids)
Treatment of Uncomplicated Vulvovaginal Candidiasis
Most can be resolved with topical OTC (cream or suppository): Miconazole, Clotrimazole, Tioconazole
Rx Agents:
Fluconazole 150 mg PO x 1 dose
Butoconazole cream
Teroconazole cream or suppository
Follow-Up for Uncomplicated Vulvovaginal Candidiasis
If symptoms persist after OTC or if you have recurrence within 2 months, see your doctor
Treatment of Recurrent Vulvovaginal Candidiasis
Can use short duration oral or topical azole therapu
May try longer duration 7-14 days of topical therapy of Fluconazole PO q72h x 3 doses
Treatment of Severe Vulvovaginal Candidiasis
Topical azole therapy x 7-14 days OR
Fluconazole 150 mg PO q72h x 2 doses
Risk Factors for Candidemia
Immunosuppression
Catheters
Prior broad-spectrum antibiotics
Intra-abdominal surgery (Candida is normal flora in GI tract)
Empiric Therapy for Candidemia
Echinocandin
Empiric therapy should be started right away
Alternative Empiric Therapy for Candidemia
Fluconazole
Lipid Formulation Amphotericin
Directed Therapy of Candidemia - C. albicans
Fluconazole IV or PO
Directed Therapy of Candidemia - C. glabrata
Echinocandin OR
Fluconazole IV or PO (depending on susceptibility)
Directed Therapy of Candidemia - C. krusei
Echinocandin
Duration of Therapy for Candidemia
2 weeks from first negative blood culture
Adjunctive Measures for Candidemia
Fundoscopic exam to rule out endophthalmitis (if confirmed, azoles preferred over echinocandin and extend therapy to 6 weeks)
IV catheter removal recommended, if catheter presumed source
Follow-up blood cultures to document eradication
Risk Factors for Invasive Aspergillosis Infection
Bone marrow transplant
Hematologic malignancy
Solid organ transplant
AIDS
Long-term steroids
First-Line Treatment of Invasive Pulmonary Aspergillosis
Voriconazole (need therapeutic drug monitoring)
Preferred Alternative Treatment for Invasive Pulmonary Aspergillosis
Amphotericin B (only if patients cannot take voriconazole)
Other Alternative Treatments for Invasive Pulmonary Aspergillosis
Isavuconazole
Voriconazole + Echinocandin (for very invasive disease)
Treatment Duration for Invasive Pulmonary Aspergillosis
Minimum 6-12 weeks
Other Management of Invasive Pulmonary Aspergillosis
Reduce immunosuppression (neutrophil recovery is the best management for this infection)
Surgery for debridement of localized disease
Secondary Prophylaxis of Invasive Pulmonary Aspergillosis
After treatment of active infection is complete, if immunosuppression persists, secondary prophylaxis should be initiated to prevent recurrence (voriconazole, posaconazole, or micafungin)
Risk Factors for Coccidiomycosis
Immunosuppression
Pregnancy
Uncontrolled diabetes
African American or Filipino
Asymptomatic Pulmonary Cocci Infection
No treatment if asymptomatic
Treatment of Symptomatic Pulmonary Cocci Infection
DOC: Fluconazole IV or PO
Itraconazole
Amphotericin B
Treatment of CNS Cocci Infection
DOC: Fluconazole IV or PO
Amphotericin IT (last resort, very low tolerability)
Treatment Duration of Cocci Infection
Minimum 3-6 months
Cocci meningitis: will be on maintenance therapy lifelong
Risk Factors for Cryptococcosis
Uncontrolled HIV
Male
Smokers
Malignancy
Lung conditions
50 + yo
Manifestations of Cryptococcosis
Pneumonia
Meningitis (most common)
Treatment on Cryptococcal Meningitis in HIV+ Pts
Three phases of therapy:
- Amphotericin B plus Flucytosine x at least 2 weeks
- Fluconazole 800 mg PO daily x 4 weeks
- Fluconazole 200 mg PO daily x 1 year (maybe longer or lifetime)
Treatment of Cryptococcal Meningitis in Non-HIV Pts
Three phases of therapy:
- Liposomal Amphotericin B PLUS Flucytosine x at least 4 weeks
- Fluconazole 400-800 mg PO daily x 8 weeks
- Fluconazole 200-400 mg pO daily x 6 months-1 year
Treatment of Mild to Moderate Pulmonary Cryptococcosis
Fluconazole PO x 6-12 months
Treatment of Severe Pulmonary Cryptococcosis
Same as Crypto meningitis
Maintenance therapy of fluconazole continued for 12 months
