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Infectious Disease > PCOL Antifungals > Flashcards

PCOL Antifungals Flashcards

1
Q

Types of Yeast

A

Candida - C. albicans, C. glabrata, C. tropicalis, C. krusei
Cryptococcus

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2
Q

Types of Mold

A

Aspergillus
Mucor
Rhizopus

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3
Q

Types of Dipmorphic Fungi

A

Histoplasma
Blastomyces
Coccidiodes

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4
Q

Polyenes Drugs

A

Ampothericin B

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5
Q

Amphotericin B Spectrum of Coverage

A
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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)

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7
Q

Amphotericin B Route of Administration

A

IV only

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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

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9
Q

Amphotericin B DDIs

A

Avoid use with concomitant nephrotoxic agents (vanco, aminoglycosides, colistin)

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10
Q

Lipid Amphotericin B Formulations Drugs

A

Abelcet and Ambisome

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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

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12
Q

When is Ambisome preferred?

A

For CNS infections

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13
Q

Triazole Drugs

A

Fluconazole

Itraconazole

Voriconazole

Posaconazole

Isavuconazole

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14
Q

Fluconazole Spectrum of Activity

A
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15
Q

Fluconazole Indications

A

Infections due to yeasts: Candida (except krusei) and Cryptococcal

Infections due to Cocci (DOC for most Cocci infections)

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16
Q

Fluconazole Route of Administration

A

PO and IV

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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

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18
Q

Fluconazole ADRs

A

Hepatotoxicity (class effect)

QT Prolongation (class effect)

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19
Q

Fluconazole DDIs

A

CYP2C19 - warfarin, phenytoin

Avoid concomitant QT prolonging meds

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20
Q

Itraconazole Spectrum of Activity

A
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21
Q

Itraconazole Indications

A

Histoplasmosis infections (outside of CNS)

Alternative for other invasive infections for invasive organisms

Onychomycosis (fungal nail infection)

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22
Q

Itraconazole Route of Administration

A

PO only (capsules and oral solution)

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23
Q

Can you switch itraconazole formulations in the middle of therapy?

A

No, they are not interchangeable because they have different bioavailabilities

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24
Q

Which formulation of itraconazole is preferred?

A

Oral solution because of better absorption

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25
Q

Does itraconazole require dose adjustments for organ dysfunction?

A

No

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26
Q

Itraconazole ADRs

A

Hepatotoxicity (class effect)

QT Prolongation (class effect)

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27
Q

Itraconazole BBWs

A

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)

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28
Q

Itraconazole Counseling Points

A

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

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29
Q

Voriconazole Spectrum of Activity

A
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30
Q

Voriconazole Indications

A

First line for Aspergillosis

Second line for yeast infections or dimorphic infections

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31
Q

Voriconazole Route of Administration

A

PO and IV

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32
Q

Voriconazole Therapeutic Drug Monitoring

A

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)
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33
Q

Voriconazole Dose Adjustments

A

Hepatic dose adjustment for Child Pugh A and B

No renal dose adjustment needed, but PO recommended in CrCl < 50 (IV formulation contains cyclodextrin)

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34
Q

Voriconazole ADRs

A

Hepatotoxicity (class effect)

QT Prolongation (class effect)

Visual disturbances

Photophobia

Hallucinations

Cutaneous malignancy (with long-term use)

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35
Q

Voriconazole DDIs

A

Contraindicated with rifampin, carbamazepine, long-acting barbiturates, and sirolimus

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36
Q

Posaconazole Spectrum of Activity

A
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37
Q

Posaconazole Indications

A

Alternative for Candida, mold, and dimorphic fungi

Prophylaxis to prevent invasive fungal infection in neutropenic host

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38
Q

Posaconazole Route of Administration

A

PO (tablets and oral suspension) and IV

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39
Q

Which posaconazole oral formulation is preferred?

A

Delayed release tablets preferred over oral suspension

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40
Q

Posaconazole ADRs

A

Hepatotoxicity (class effect)

QT Prolongation (class effect)

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41
Q

Posaconazole Dose Adjustments for Organ Dysfunction

A

No dose adjustment for renal or hepatic dysfunction

PO formulation recommended in pts with CrCl < 50 (IV formulation contains cyclodextrin)

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42
Q

Posaconazole Patient Counseling

A

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

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43
Q

Isuvuconazole Spectrum of Activity

A
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44
Q

Isuvuconazole Indications

A

Alternative for invasive Aspergillosis or Mucormycosis infections

Should NOT be used for invasive candidiasis

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45
Q

Isuvuconazole Route of Administration

A

PO or IV

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46
Q

Isuvuconazole Dose Adjustment for Organ Dysfunction

A

Dose adjustment not needed in renal or hepatic dysfunctioni

Use with caution in Child Pugh Class. C

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47
Q

Isuvuconazole ADRs

A

Hepatotoxicity (class effect)

QT shortening - use caution in familial short QT syndrome

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48
Q

Isuvuconazole DDIs

A

Contraindicated with Rifampin and Lopinavir/ritonavir

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49
Q

Echinocandins Drugs

A

Caspofungin

Micafungin

Anidulafungin

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50
Q

Echinocandins Spectrum of Activity

A
51
Q

Echinocandins Indications

A

Candidemia (Candida bloodstream infection)

Invasive Candidiasis (NOT CNS infections)

Alternative therapy for Aspergillosis

52
Q

Echinocandins Dose Adjustment for Organ Dysfunction

A

Do not require dose adjustment for renal or hepatic dysfunction

Good alternative to azoles in pts with hepatic dysfunction

53
Q

Echinocandins Route of Administration

A

IV only

54
Q

Caspofungin DDIs

A

Cyclosporine, tacrolimus, rifampin, phenytoin

55
Q

Micafungin DDIs

A

Sirolimus, nifedipine

56
Q

Anidulafungin DDIs

A

Cyclosporine

57
Q

Echinocandins ADRs

A

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
Q

Flucytosine Spectrum of Activity

A
59
Q

Flucytosine Indications

A

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
Q

Flucytosine Route of Administration

A

PO only

61
Q

Flucytosine Dose Adjustment for Organ Dysfunction

A

Dose adjustment required for CrCl < 40

Caution with concomitant hepatotoxic agents

62
Q

Flucytosine ADRs

A

Bone marrow suppression (can be treatment limiting)

Hepatotoxicity (not usually treatment limiting)

63
Q

Nystatin Indications

A

Mild oral candidiasis (thrush)

64
Q

Nystatin Route of Administration

A

Oral suspension

65
Q

Nystatin Patient Counseling

A

Wait 20-30 min to eat before taking Nystatin; brush teeth at least 30 min after taking because it contains sugar

66
Q

Terbinafine Indications

A

Onychomycosis (fungal nail infection)

Tinea infections that do not respond to topical therapy or extensive infection

67
Q

Terbinafine Route of Administration

A

PO

68
Q

Terbinafine Contraindication

A

Contraindicated in chronic or active liver disease

69
Q

Terbinafine ADRs

A

Hepatotoxicity - main toxicity we worry about

Headache - most common

Taste disturbance

May cause decrease in lymphocyte or neutrophil count

70
Q

Terbinafine Monitoring Parameters

A

AST/ALT

Taste disturbance

CBC if duration > 6 months and history of preexisting immunosuppression

71
Q

Griseofulvin Indications

A

Onychomycosis (fungal nail infection)

Tinea infections that do not respond to topical therapy or extensive infection

72
Q

Griseofulvin Route of Administration

A

PO (oral suspension and tablets)

73
Q

Griseofulvin Contraindications

A

Chronic or active liver disease

Pregnancy

Porphyria

Males should avoid fathering a child for 6 months after taking

74
Q

Griseofulvin Patient Counseling

A

Take with a fatty meal to increase absorption and decrease GI upset

Avoid alcohol - can cause disulfiram reaction

75
Q

Antifungals Safe in Pregnancy

A

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
Q

Antifungals NOT Safe in Pregnancy

A

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
Q

Non-invasive Candidiasis

A

Thrush - mouth or esophagus

Vulvovaginal candidiasis

78
Q

Signs and symptoms of oral thrush

A

Curdlike white patches over tongue - “cottony mouth”

79
Q

Risk factors for oral thrush

A

Use of inhaled steroids

Denture use

Xerostomia (dry mouth)

Malignancy

AIDS

80
Q

Signs and symptoms of esphageal thrush

A

White plaque in esophagus

Painful swallowing, feeling of obstruction when swallowing

Substernal chest pain

N/V

81
Q

Risk factors for esophageal thrush

A

Malignancy

AIDS

Long-term Omeprazole use

82
Q

Treatment of mild oral thrush

A

Clotrimazole troches

Miconazole mucoadhesive buccal tablets

Nystatin oral suspension

83
Q

Treatment of moderate to severe oral thrush

A

Fluconazole PO (systemic)

84
Q

Treatment Duration for Oral Thrush

A

7-14 days

85
Q

What to do if refractory to fluconazole in treatment of oral thrush?

A

Itraconazole oral solution or Posaconazole oral suspension

86
Q

Treatment of esophageal thrush

A

Systemic therapy always needed

Preferred: Fluconazole PO or IV

Alternative: Echinocandin IV

87
Q

Treatment duration of esophageal thrush

A

14-21 days

88
Q

What to do if refractory to fluconazole in treatment of esophageal thrush?

A

Itraconazole oral solution

Posaconazole oral suspension

Voriconazole

89
Q

Common Pathogen Causing Vulvovaginal Candidiasis

A

Candida albicans

90
Q

Risk Factors for Developing Vulvovaginal Candidiasis

A

Diabetes

Antibiotic therapy

Pregnancy

Some birth control pills

91
Q

Signs of Vulvovaginal Candidiasis

A

Thick, curdy, odorless vaginal discharge

92
Q

Uncomplicated Vulvovaginal Candidiasis

A

Sporadic or infrequent VVC AND

Mild-moderate VVC AND

Likely to be C. albicans AND

Non-immunocompromised

93
Q

Complicated Vulvovaginal Candidiasis

A

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
Q

Treatment of Uncomplicated Vulvovaginal Candidiasis

A

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
Q

Follow-Up for Uncomplicated Vulvovaginal Candidiasis

A

If symptoms persist after OTC or if you have recurrence within 2 months, see your doctor

96
Q

Treatment of Recurrent Vulvovaginal Candidiasis

A

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
Q

Treatment of Severe Vulvovaginal Candidiasis

A

Topical azole therapy x 7-14 days OR

Fluconazole 150 mg PO q72h x 2 doses

98
Q

Risk Factors for Candidemia

A

Immunosuppression

Catheters

Prior broad-spectrum antibiotics

Intra-abdominal surgery (Candida is normal flora in GI tract)

99
Q

Empiric Therapy for Candidemia

A

Echinocandin

Empiric therapy should be started right away

100
Q

Alternative Empiric Therapy for Candidemia

A

Fluconazole

Lipid Formulation Amphotericin

101
Q

Directed Therapy of Candidemia - C. albicans

A

Fluconazole IV or PO

102
Q

Directed Therapy of Candidemia - C. glabrata

A

Echinocandin OR

Fluconazole IV or PO (depending on susceptibility)

103
Q

Directed Therapy of Candidemia - C. krusei

A

Echinocandin

104
Q

Duration of Therapy for Candidemia

A

2 weeks from first negative blood culture

105
Q

Adjunctive Measures for Candidemia

A

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
Q

Risk Factors for Invasive Aspergillosis Infection

A

Bone marrow transplant

Hematologic malignancy

Solid organ transplant

AIDS

Long-term steroids

107
Q

First-Line Treatment of Invasive Pulmonary Aspergillosis

A

Voriconazole (need therapeutic drug monitoring)

108
Q

Preferred Alternative Treatment for Invasive Pulmonary Aspergillosis

A

Amphotericin B (only if patients cannot take voriconazole)

109
Q

Other Alternative Treatments for Invasive Pulmonary Aspergillosis

A

Isavuconazole

Voriconazole + Echinocandin (for very invasive disease)

110
Q

Treatment Duration for Invasive Pulmonary Aspergillosis

A

Minimum 6-12 weeks

111
Q

Other Management of Invasive Pulmonary Aspergillosis

A

Reduce immunosuppression (neutrophil recovery is the best management for this infection)

Surgery for debridement of localized disease

112
Q

Secondary Prophylaxis of Invasive Pulmonary Aspergillosis

A

After treatment of active infection is complete, if immunosuppression persists, secondary prophylaxis should be initiated to prevent recurrence (voriconazole, posaconazole, or micafungin)

113
Q

Risk Factors for Coccidiomycosis

A

Immunosuppression

Pregnancy

Uncontrolled diabetes

African American or Filipino

114
Q

Asymptomatic Pulmonary Cocci Infection

A

No treatment if asymptomatic

115
Q

Treatment of Symptomatic Pulmonary Cocci Infection

A

DOC: Fluconazole IV or PO

Itraconazole

Amphotericin B

116
Q

Treatment of CNS Cocci Infection

A

DOC: Fluconazole IV or PO

Amphotericin IT (last resort, very low tolerability)

117
Q

Treatment Duration of Cocci Infection

A

Minimum 3-6 months

Cocci meningitis: will be on maintenance therapy lifelong

118
Q

Risk Factors for Cryptococcosis

A

Uncontrolled HIV

Male

Smokers

Malignancy

Lung conditions

50 + yo

119
Q

Manifestations of Cryptococcosis

A

Pneumonia

Meningitis (most common)

120
Q

Treatment on Cryptococcal Meningitis in HIV+ Pts

A

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
Q

Treatment of Cryptococcal Meningitis in Non-HIV Pts

A

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
Q

Treatment of Mild to Moderate Pulmonary Cryptococcosis

A

Fluconazole PO x 6-12 months

123
Q

Treatment of Severe Pulmonary Cryptococcosis

A

Same as Crypto meningitis

Maintenance therapy of fluconazole continued for 12 months

Infectious Disease (15 decks)

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