PCOL Antifungals Flashcards
(123 cards)
1
Q
Types of Yeast
A
Candida - C. albicans, C. glabrata, C. tropicalis, C. krusei
Cryptococcus
2
Q
Types of Mold
A
Aspergillus
Mucor
Rhizopus
3
Q
Types of Dipmorphic Fungi
A
Histoplasma
Blastomyces
Coccidiodes
4
Q
Polyenes Drugs
A
Ampothericin B
5
Q
Amphotericin B Spectrum of Coverage
A
6
Q
Amophotericin B Indications
A
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)
7
Q
Amphotericin B Route of Administration
A
IV only
8
Q
Amphotericin B ADRs
A
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
9
Q
Amphotericin B DDIs
A
Avoid use with concomitant nephrotoxic agents (vanco, aminoglycosides, colistin)
10
Q
Lipid Amphotericin B Formulations Drugs
A
Abelcet and Ambisome
11
Q
Lipid Amphotericin B Advantages
A
Lower risk of infusion-related reactions and nephrotoxicity, but still some risk
Allow us to give higher doses of Amphotericin
12
Q
When is Ambisome preferred?
A
For CNS infections
13
Q
Triazole Drugs
A
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Isavuconazole
14
Q
Fluconazole Spectrum of Activity
A
15
Q
Fluconazole Indications
A
Infections due to yeasts: Candida (except krusei) and Cryptococcal
Infections due to Cocci (DOC for most Cocci infections)
16
Q
Fluconazole Route of Administration
A
PO and IV
17
Q
Fluconazole Dose Adjustments for Organ Dysfunction
A
Renal dose adjustment required if CrCl < 50 (decrease dose by 50%)
ONLY azole that requires renal dose adjustment
18
Q
Fluconazole ADRs
A
Hepatotoxicity (class effect)
QT Prolongation (class effect)
19
Q
Fluconazole DDIs
A
CYP2C19 - warfarin, phenytoin
Avoid concomitant QT prolonging meds
20
Q
Itraconazole Spectrum of Activity
A
21
Q
Itraconazole Indications
A
Histoplasmosis infections (outside of CNS)
Alternative for other invasive infections for invasive organisms
Onychomycosis (fungal nail infection)
22
Q
Itraconazole Route of Administration
A
PO only (capsules and oral solution)
23
Q
Can you switch itraconazole formulations in the middle of therapy?
A
No, they are not interchangeable because they have different bioavailabilities
24
Q
Which formulation of itraconazole is preferred?
A
Oral solution because of better absorption
25
Does itraconazole require dose adjustments for organ dysfunction?
No
26
Itraconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
27
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)
28
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
29
Voriconazole Spectrum of Activity
30
Voriconazole Indications
First line for **Aspergillosis**
Second line for yeast infections or dimorphic infections
31
Voriconazole Route of Administration
PO and IV
32
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)
33
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)
34
Voriconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
**Visual disturbances**
**Photophobia**
**Hallucinations**
**Cutaneous malignancy** (with long-term use)
35
Voriconazole DDIs
Contraindicated with **rifampin, carbamazepine, long-acting barbiturates**, and **sirolimus**
36
Posaconazole Spectrum of Activity
37
Posaconazole Indications
Alternative for Candida, mold, and dimorphic fungi
Prophylaxis to prevent invasive fungal infection in neutropenic host
38
Posaconazole Route of Administration
PO (tablets and oral suspension) and IV
39
Which posaconazole oral formulation is preferred?
Delayed release tablets preferred over oral suspension
40
Posaconazole ADRs
Hepatotoxicity (class effect)
QT Prolongation (class effect)
41
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)
42
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
43
Isuvuconazole Spectrum of Activity
44
Isuvuconazole Indications
Alternative for invasive Aspergillosis or Mucormycosis infections
Should NOT be used for invasive candidiasis
45
Isuvuconazole Route of Administration
PO or IV
46
Isuvuconazole Dose Adjustment for Organ Dysfunction
Dose adjustment not needed in renal or hepatic dysfunctioni
Use with caution in Child Pugh Class. C
47
Isuvuconazole ADRs
Hepatotoxicity (class effect)
**QT shortening** - use caution in familial short QT syndrome
48
Isuvuconazole DDIs
Contraindicated with **Rifampin** and **Lopinavir/ritonavir**
49
Echinocandins Drugs
Caspofungin
Micafungin
Anidulafungin
50
Echinocandins Spectrum of Activity
51
Echinocandins Indications
Candidemia (Candida bloodstream infection)
Invasive Candidiasis (NOT CNS infections)
Alternative therapy for Aspergillosis
52
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
53
Echinocandins Route of Administration
IV only
54
Caspofungin DDIs
Cyclosporine, tacrolimus, rifampin, phenytoin
55
Micafungin DDIs
Sirolimus, nifedipine
56
Anidulafungin DDIs
Cyclosporine
57
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
58
Flucytosine Spectrum of Activity
59
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
60
Flucytosine Route of Administration
PO only
61
Flucytosine Dose Adjustment for Organ Dysfunction
Dose adjustment required for CrCl \< 40
Caution with concomitant hepatotoxic agents
62
Flucytosine ADRs
**Bone marrow suppression** (can be treatment limiting)
Hepatotoxicity (not usually treatment limiting)
63
Nystatin Indications
Mild oral candidiasis (thrush)
64
Nystatin Route of Administration
Oral suspension
65
Nystatin Patient Counseling
Wait 20-30 min to eat before taking Nystatin; brush teeth at least 30 min after taking because it contains sugar
66
Terbinafine Indications
Onychomycosis (fungal nail infection)
Tinea infections that do not respond to topical therapy or extensive infection
67
Terbinafine Route of Administration
PO
68
Terbinafine Contraindication
Contraindicated in chronic or active liver disease
69
Terbinafine ADRs
Hepatotoxicity - main toxicity we worry about
Headache - most common
Taste disturbance
May cause decrease in lymphocyte or neutrophil count
70
Terbinafine Monitoring Parameters
AST/ALT
Taste disturbance
CBC if duration \> 6 months and history of preexisting immunosuppression
71
Griseofulvin Indications
Onychomycosis (fungal nail infection)
Tinea infections that do not respond to topical therapy or extensive infection
72
Griseofulvin Route of Administration
PO (oral suspension and tablets)
73
Griseofulvin Contraindications
Chronic or active liver disease
Pregnancy
Porphyria
Males should avoid fathering a child for 6 months after taking
74
Griseofulvin Patient Counseling
Take with a fatty meal to increase absorption and decrease GI upset
Avoid alcohol - can cause disulfiram reaction
75
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
76
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
77
Non-invasive Candidiasis
Thrush - mouth or esophagus
Vulvovaginal candidiasis
78
Signs and symptoms of oral thrush
Curdlike white patches over tongue - “cottony mouth”
79
Risk factors for oral thrush
Use of inhaled steroids
Denture use
Xerostomia (dry mouth)
Malignancy
AIDS
80
Signs and symptoms of esphageal thrush
White plaque in esophagus
Painful swallowing, feeling of obstruction when swallowing
Substernal chest pain
N/V
81
Risk factors for esophageal thrush
Malignancy
AIDS
Long-term Omeprazole use
82
Treatment of mild oral thrush
Clotrimazole troches
Miconazole mucoadhesive buccal tablets
Nystatin oral suspension
83
Treatment of moderate to severe oral thrush
Fluconazole PO (systemic)
84
Treatment Duration for Oral Thrush
7-14 days
85
What to do if refractory to fluconazole in treatment of oral thrush?
Itraconazole oral solution or Posaconazole oral suspension
86
Treatment of esophageal thrush
Systemic therapy always needed
Preferred: Fluconazole PO or IV
Alternative: Echinocandin IV
87
Treatment duration of esophageal thrush
14-21 days
88
What to do if refractory to fluconazole in treatment of esophageal thrush?
Itraconazole oral solution
Posaconazole oral suspension
Voriconazole
89
Common Pathogen Causing Vulvovaginal Candidiasis
Candida albicans
90
Risk Factors for Developing Vulvovaginal Candidiasis
Diabetes
Antibiotic therapy
Pregnancy
Some birth control pills
91
Signs of Vulvovaginal Candidiasis
Thick, curdy, odorless vaginal discharge
92
Uncomplicated Vulvovaginal Candidiasis
Sporadic or infrequent VVC AND
Mild-moderate VVC AND
Likely to be C. albicans AND
Non-immunocompromised
93
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)
94
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
95
Follow-Up for Uncomplicated Vulvovaginal Candidiasis
If symptoms persist after OTC or if you have recurrence within 2 months, see your doctor
96
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
97
Treatment of Severe Vulvovaginal Candidiasis
Topical azole therapy x 7-14 days OR
Fluconazole 150 mg PO q72h x 2 doses
98
Risk Factors for Candidemia
Immunosuppression
Catheters
Prior broad-spectrum antibiotics
Intra-abdominal surgery (Candida is normal flora in GI tract)
99
Empiric Therapy for Candidemia
Echinocandin
Empiric therapy should be started right away
100
Alternative Empiric Therapy for Candidemia
Fluconazole
Lipid Formulation Amphotericin
101
Directed Therapy of Candidemia - C. albicans
Fluconazole IV or PO
102
Directed Therapy of Candidemia - C. glabrata
Echinocandin OR
Fluconazole IV or PO (depending on susceptibility)
103
Directed Therapy of Candidemia - C. krusei
Echinocandin
104
Duration of Therapy for Candidemia
2 weeks from first negative blood culture
105
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
106
Risk Factors for Invasive Aspergillosis Infection
Bone marrow transplant
Hematologic malignancy
Solid organ transplant
AIDS
Long-term steroids
107
First-Line Treatment of Invasive Pulmonary Aspergillosis
Voriconazole (need therapeutic drug monitoring)
108
Preferred Alternative Treatment for Invasive Pulmonary Aspergillosis
Amphotericin B (only if patients cannot take voriconazole)
109
Other Alternative Treatments for Invasive Pulmonary Aspergillosis
Isavuconazole
Voriconazole + Echinocandin (for very invasive disease)
110
Treatment Duration for Invasive Pulmonary Aspergillosis
Minimum 6-12 weeks
111
Other Management of Invasive Pulmonary Aspergillosis
Reduce immunosuppression (neutrophil recovery is the best management for this infection)
Surgery for debridement of localized disease
112
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)
113
Risk Factors for Coccidiomycosis
Immunosuppression
Pregnancy
Uncontrolled diabetes
African American or Filipino
114
Asymptomatic Pulmonary Cocci Infection
No treatment if asymptomatic
115
Treatment of Symptomatic Pulmonary Cocci Infection
DOC: Fluconazole IV or PO
Itraconazole
Amphotericin B
116
Treatment of CNS Cocci Infection
DOC: Fluconazole IV or PO
Amphotericin IT (last resort, very low tolerability)
117
Treatment Duration of Cocci Infection
Minimum 3-6 months
Cocci meningitis: will be on maintenance therapy lifelong
118
Risk Factors for Cryptococcosis
Uncontrolled HIV
Male
Smokers
Malignancy
Lung conditions
50 + yo
119
Manifestations of Cryptococcosis
Pneumonia
Meningitis (most common)
120
Treatment on Cryptococcal Meningitis in HIV+ Pts
Three phases of therapy:
1. Amphotericin B plus Flucytosine x at least 2 weeks
2. Fluconazole 800 mg PO daily x 4 weeks
3. Fluconazole 200 mg PO daily x 1 year (maybe longer or lifetime)
121
Treatment of Cryptococcal Meningitis in Non-HIV Pts
Three phases of therapy:
1. Liposomal Amphotericin B PLUS Flucytosine x at least 4 weeks
2. Fluconazole 400-800 mg PO daily x 8 weeks
3. Fluconazole 200-400 mg pO daily x 6 months-1 year
122
Treatment of Mild to Moderate Pulmonary Cryptococcosis
Fluconazole PO x 6-12 months
123
Treatment of Severe Pulmonary Cryptococcosis
Same as Crypto meningitis
Maintenance therapy of fluconazole continued for 12 months
