Term
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Definition
round/oval, smooth flat colonies that reproduce by budding;
e.g. Candida, Cryptococcus |
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Term
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Definition
appear fuzzy, growth through branching;
e.g. Aspergillus spp., Mucor |
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Term
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Definition
exist as yeast or mold depending on environment;
e.g. Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum |
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Term
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Definition
| resistance develops rapidly |
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Term
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Definition
resistance is stable over time (generally species predicts susceptibility);
Pt Populations:
- immunocompromised, healthcare exposure;
Incidence is increasing; |
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Term
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Definition
in healthcare setting, 4th most common organism isolated from blood;
- commonly catheter or GI source;
Remove central venous catheter if able to!!! |
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Term
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Definition
Fluconazole-susceptible: LD - Fluconazole 800 mg, MD - Fluconazole 400 mg daily;
Echinocandins:
- DOC empirically if severe disease/recent azole exposure
- DOC for fluconazole-resistant species;
Duration (if uncomplicated): 2 weeks starting from 1st negative culture |
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Term
| Tx of Candidiasis in Neutropenic Pts |
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Definition
empiric therapy:
- amphotericin B, echinocandin, or voriconazole;
Duration (if uncomplicated): 2 weeks after 1st negative blood culture |
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Term
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Definition
opportunistic infection;
- decreasing incidence in US since combined antiretroviral therapy (cART), still common in developing countries;
Presents as meningitis or pneumonia;
Meningitis has 20% mortality rate WITH treatment; |
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Term
| Treatment of Cryptococcal Meningitis |
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Definition
amphotericin B:
- liposomal 3-4 mg/kg/day
OR
- deoxycholate 0.7-1 mg/kg/day
PLUS
Flucytosine 100 mg/kg/day divided q6 hr x 2 wks
Followed by:
Fluconazole 400 mg/day x 8 wks
Maintenance:
- fluconazole 200 mg/day x >=1 year |
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Term
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Definition
opportunistic infection;
presents as: Invasive Pulmonary Aspergillosis, allergic bronchopulmonary aspergillus, fungal bails, other manifestations; |
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Term
| Risk Factors for Aspergillosis Infection |
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Definition
Prolonged neutropenia ANC < 100;
hematologic malignancies;
AML - Acute Myeloid Leukemia;
BMT - Bone Marrow Transplant;
SOT (esp. lung) - Solid Organ Transplant;
steroid use; |
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Term
| Treatment of Aspergillosis |
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Definition
Active:
- VORICONAZOLE
- amphotericin B
- echinocandins |
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Term
| Dimorphic Fungi infections caused by Blastomycete dermatitidis |
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Definition
Midwestern states, Chicago, Michigan;
Found in soil;
Presents as pulmonary disease;
Induction Treatment in Severe Disease:
- initial: amphotericin B (less severe = triazole);
Consolidation Phase:
- itraconazole, fluconazole (CNS), or voriconazole |
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Term
| Dimorphic Fungi infections caused by Histoplasmata capsulatum |
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Definition
Found in Mississippi, Ohio, central Indiana, St. Lawrence River Valley;
Found primarily in soil & avian droppings;
Induction Tx in Severe Disease:
- amphotericin B (less severe, start with triazole);
Consolidation Phase:
- itraconazole |
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Term
| Dimorphic Fungi infections caused by Coccidioides spp. |
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Definition
Found in Southwest (AZ, NM, San Joaquin Valley);
Found primarily in soil;
Induction Treatment in Severe Disease:
- amphotericin B (triazole in less severe dx);
Consolidation Phase:
- itraconazole or fluconazole |
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Term
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Definition
seen in immunocompromised;
Commonly presents as Invasive Sinus Disease;
Primary Treatment:
- aggressive surgery
- restoration of immune system
Treatment Options:
- amphotericin B
- echinocandins
- posaconazole
High morbidity/mortality |
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Term
| Goals of Antifungal Therapy |
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Definition
| decrease morbidity/mortality |
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Term
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Definition
Resolution of Signs/Symptoms of infection:
- resolution in diagnostic imaging;
- reoslution of hallmarks: leukocytosis, fever, inflammation;
- improved oxygenation;
- improved mental status;
- decrease in antigen burden: (1,3)-beta-D-glucan, galactomannan, urine antigens, cryptococcal antigens |
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Term
| Choice of Empiric Antifungal Therapy for Candidemia |
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Definition
Based on:
- exposure to fluconazle within past 3 months?
- local microbiology data;
- severity of illness;
- Pharmacotherapeutic issues: interacting meds, comorbid conditions, absorption, hx of intolerance of antifungals |
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Term
| Amphotericin B (deoxycholate, liposomal [AmBisome], lipid complex [Abelcet]) |
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Definition
MoA: forms aggregates in cell membrane with ergosterol, leading to pores that cause leakage of cellular contents;
Broadest spectrum agent:
- Candida spp., Aspergillus spp., Cryptococcus spp., Endemic fungi, Mucor;
Fungicidal;
Dosing:
- liposomal: 3-4 mg/kg
- lipid complex: 5 mg/kg
- deoxycholate: 0.7-1.0 mg/kg)
- based on total body weight
- infuse in D5W
- NO dose adjustment in renal/hepatic dysfunction (consider dose decrease if renal toxicity occurs); |
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Term
| ADRs & Monitoring for Amphotericin B |
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Definition
Most common: renal toxicity, electrolyte wasting (Mg, K);
- Monitor SCr, BUN, Mg, K;
- hydrate w/ minimum of 1 L NS/day;
- replete electrolytes aggressively;
Infusion-related rxns 1st 3-5 days (fevers, chills, rigors, thrombophlebitis):
- premedicate w/ diphenhydramine, APAP, steroids (hydrocortisone 0.7 mg/kg/day), heparin 100 units if administered peripherally;
Lipid formulations --> less renal toxicity & infusion-related rxns |
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Term
| Monitoring Parameters for Amphotericin B |
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Definition
| SCr, Urine Output, K, Mg, Ca, LFTs |
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Term
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Definition
| Drug of Choice for invasive candidiasis in pregnancy |
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Term
| Drug Interactions with Amphotericin B |
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Definition
renal toxicity exacerbated by concomitant nephrotoxic agents (tacrolimus, cyclosporine, aminoglycosides);
- Digoxin: potentiation of effects in setting of hypokalemia; |
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Term
| Triazoles - ketoconazole (Nizoral), itraconazole (Sporanox), fluconazole (Diflucan), voriconazole (Vfend), posaconazole (Noxafil) |
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Definition
| MoA: blocks biosynthesis of ergosterol, a sterol needed for cell membrane stability via fungal CYP450 inhibition |
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Term
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Definition
Spectrum:
- Endemic fungi (Histoplasmata capsulatum)
- Candida spp.
- Aspergillus spp.
Dosing:
- LD: 300 mg PO TID x 3 days, MD: 200 mg PO BID
- capsules: take w/ meal or acidic environment (cola) - do NOT use PPI or H2RA;
- SOlution: use in fasting state;
Nonlinear PK
T1/2 = 40 hrs;
ADRs: N/V, increased LFTs, hypokalemia, increased TGs, rash, neg. inotropic activity;
D-D Interactions: CYP3A4 substrate & inhibitor - C/I w/ statins (except pravastatin);
Monitoring:
- LFTs, S/Sx of CHF, rash;
TDM: Trough after min. of 5-7 days
Target: >1 mg/L via HPLC;
Preg. Cat. C |
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Term
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Definition
Spectrum:
- Candida spp.
- Cryptococcus spp.
- Endemic fungi;
Dosing:
- LD: 400-800 mg PO/IV, then MD: 200-400 mg PO/IV;
- Invasive Candidiasis: 800 mg LD followed by 400 mg/day MD;
- Dose adjustment REQUIRED in RENAL dysfunction;
Biovailability: >=90%
T1/2 = 30 hrs;
ADRs: extremely well tolerated, maybe some N/V, increased LFT, HA, reversible alopecia;
WEAK inhibitor of CYP450;
Monitor:
- LFTs, rash, QT interval in high risk pts;
Preg. Cat C (150 mg single dose OK) |
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Term
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Definition
Spectrum:
- Aspergillosis spp. (most common indication)
- Candida spp.
- Fusarium spp. & Scedosporium spp.;
Dosing:
- 6 mg/kg q12 hrs PO/IV x 2 doses followed by 4 mg/kg q12 hr;
- REQUIRES dose adjustment in mild-moderate liver dysfunction (Child-Pugh class A/B, standard LD followed by 50% normal MD);
T1/2 = 6 hrs;
Nonlinear PK;
ADRs: visual disturbances, hepatotoxicity, skin rash, photosensitivity, prolonged QT interval & Torsades de Pointes;
- Avoid IV in pts w/ CrCl <50 mL/min --> accumulation & nephrotoxicity;
D-D Interactions: metabolized by CYP2C19;
Monitor: LFTs, bilirubin, renal fcn, visual fcn;
TDM:
C/I in pregnancy |
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Term
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Definition
Spectrum:
- Candida spp.
- Aspergillus spp.
- Mucor
- Endemic fungi;
Dosing:
- 400 mg PO BID or 200 mg PO 3-4x/day
- absorption requires acidic environment, high fat meal;
- NO dose adjustment in renal/hepatic dysfunction;
Linear PK
T1/2 = 35 hrs;
ADRs: extremely well tolerated, maybe some N/V, increased LFT, HA, reversible alopecia;
D-D Interactions: NOT metabolized by CYP; INHIBITS CYP3A4;
Monitor: PO intake, diarrhea, LFTs, bilirubin, Mg, Ca;
TDM: Trough after 7 days, TARGET: >0.7-1.25 mg/L;
Preg. Cat. C |
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Term
| Echinocandins - anidulafungin (Eraxis), micafungin (Mycamine), caspofungin (Cancidas) |
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Definition
MoA: disrupt function of the (1,3)-beta-D-glucan synthase complex;
Spectrum:
- Primary - Candida spp.
- Aspergillus spp.
- Less activity: Fusarium spp., Cryptococcus spp;
Dosing:
- available IV only, requires LD (except M);
- once daily dosing;
- NO adjustment in RENAL dysfunction;
- C requires adjustment in chronic liver disease;
ADRs: elevated LFTs;
Drug Interactions: cyclosporine, tacrolimus;
Monitor: CBC, LFTs;
Does NOT penetrate urinary tract significantly; |
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Term
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Definition
MoA: disrupts RNA & DNA synthesis;
Spectrum:
- adjuvant in cryptococcal meningitis;
- active against ALL Candida spp. w/ exception of C. krusei;
Dosing:
- 100-150 mg/kg/day IV/PO in 4 divided doses
- dosing adjustment REQUIRED for RENAL dysfunction;
ADRs: rash, diarrhea, liver toxicity, hematological toxicity;
Monitor: SCr, CBC, Urine Output, LFTs, serum levels twice weekly;
TDM: Peak after 3-5 days (2 hrs post-dose), Target: 30-80 mg/L;
C/I in pregnancy |
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Term
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Definition
indicative of fungal disease;
- collection/processing issues; |
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Term
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Definition
useful in aspergillus;
may be decrease if treated or immunocompromised;
- pip/tazo & amox/clav can cause false-(+); |
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Term
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Definition
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