11 - Invasive Fungal Infections Flashcards
List the type of infections associated with candida
- Mucosal candidiasis such as oropharyngeal, esophageal, vulvovaginitis
- Candidemia, 4th most common cause of blood stream infection
- Invasive candidiasis (i.e. acute disseminated) involves visceral sites/organ
- Hepatosplenic candidiasis
What is the most common species of Candida
Candida albicans (>50%)
______ prophylaxis/pre-emptive use, increases occurrence of non-albicans
Fluconazole
______ = emerging HCA pathogen with MDR (multi drug resistance)
C. auris
What are the risk factors for developing a candidal infection ?
- ICU > 4 days, septic shock, liver transplant, peritoneal dialysis-related peritonitis
- severe pancreatitis, GI surgery particularly if associated with leak
- immunocompromised especially due to hematologic malignancy, chemotherapy, transplant, immunosuppression, corticosteroids
- central venous catheter
- broad spectrum antibiotics
Describe the basis for diagnosing candidiasis
- Culture
- Microscopic visualization (yeasts are bigger so you can see them under a microscope)
- Histopathology critical for deep-seated infections and particularly mold infections
Describe the clinical signs and symptoms of candidiasis
- Endophthalmitis involving choroid and retina, with fluffy yellow-white lesions +/- vitrifies or retinal hemorrhages; dilated funduscopic exam indicated in all cases of candidemia
- Skin lesions with pustules on erythematous base; scrape sample or punch biopsy for histopathology and culture
- Hepatosplenic micro-abscesses, present with persistent fever, RQ pain, increased ALP
What is the prognosis of Candidemia ?
30-40% mortality, increase 3x with delay in therapy >12-24 hours (lower for C. parapsilosis)
Outline the anti fungal therapy for treating candidemia in NON-neutropenic patients
Prompt anti fungal therapy, remove/replace catheter if that is the source
Treat with: Echinocandin (class of AB) -Anidulafungin -Caspofungin -Micafungin
What do you treat Candida with for a non-crticially ill, non-invasive and without risk factors for Fluconazole-R ?
Fluconazole
- 800 mg (12mg/kg) po/iv LOAD
- 400mg (6mg/kg) q24h
What is an alternative (either for intolerance, resistance or pregnancy) for treating candidal infections ?
Amphotericin B
- deoxycholate
- liposomal preparation
When would you consider PO-step down therapy from IV therapy (Echinocandin or AmphoB) to Fluconazole
After 5-7 days if symptoms resolved and clinically stable, Fluconazole-S isolate and negative repeat blood culture
What is the duration of treatment for NON-neutropenic patients ?
2 weeks after negative repeat blood culture
Outline the anti fungal therapy for treating candidemia in neutropenic patients.
Prompt anti fungal therapy, more likely GI than CVC source, consider granulocyte colony-stimulating factors/granulocyte infusions if persistent infection and prolonged neutropenia
-Treat with Echinocandin
Non-neutropenic patient - most likely from a ____ source
CVC
Neutropenic patient - most likely from a ___ source
GI
Alternative for intolerance, resistance or pregnancy ?
AmphoB
What can we add for additional fungal/mold coverage ?
Voriconazole
Duration of treatment for a candidal infection for neutropenic patients
2 weeks after negative repeat blood culture, symptoms resolved and neutropenia resolved (ANC > 500)
What is the 2nd most common Candida ?
C. glabrata
What is the treatment for C. glabrata ?
- Dose-dependent anti fungal activity
- Increasing Flucon-R (>10%)
- Emerging Echino-R
-Try Echinocandin first (HD)
- *C. glabrata is 100% susceptible to fluconazole but at a HIGH DOSE (800mg q24h)
- *100% susceptible dependent on high dose
Alternatives for treating C. glabrata ?
- AmphoB (HD)
- Fluconazole (HD 800 mg q24h)
- Voriconizole (200-300 mg q12h)
What is the 3rd most common Candida ?
C. krusei
Describe C. krusei
- considered intrinsically fluconazole-R
- relatively high AmphoB MICs
How do you treat C. krusei ?
Echinocandin
- Anidulafungin
- Caspofungin
- Micafungin
What are alternatives for treating C. krusei ?
- Voriconazole (if susceptible)
- AmphoB (HD)
Side effect of AmphoB ?
nephrotoxicity
What are special considerations in treating invasive candidiasis (like things that involve the eye) ?
Prompt, aggressive and prolonged anti fungal therapy guided by patient characteristics, clinical status, site of infection and treatment response
**Echinocandins do not penetrate the eye, therefore fluconazole is drug of choice.
What is the role of empirical anti fungal therapy for candidiasis?
-Initiate therapy, prior to definitive diagnosis for suspected infection based on preliminary microbiology or histopathology for persistent fever despite broad-spectrum antibiotics in high-risk patient (critically ill ICU, neutropenic fever, immunocompromised, total parenteral nutrition, recent GI surgery, candida colonization)
What 2 agents can be used as empirical anti fungal therapy for candidiasis ?
- Echinocandin
- Fluconazole
What is an alternative for empirical antifungal therapy for candidiasis ?
AmphoB
-covers mold
What is each triazole approved for:
Fluconazole
-oropharyngeal, esophageal and invasive candidiasis; PROPHYLAXIS
What is each triazole approved for:
Itraconazole
-oropharyngeal, esophageal candidiasis
What is each triazole approved for:
Voriconazole
-esophageal and invasive candidiasis
What is each triazole approved for:
Posaconazole
oropharyngeal candidiasis; PROPHYLAXIS
What is aspergillosis?
-spore-forming mold, environmental exposure; most commonly A fumigatus or A. flavus
Aspergillosis:
Significantly ________ patients including hematologic malignancy, transplants (BMT, SOT), prolonged neutropenia
immunocompromised
Describe the treatment of invasive pulmonary aspergillosis
prompt anti fungal therapy, source control, consider GCSF/granulocyte infusions
What is the 1st line for treating invasive pulmonary aspergillosis?
Voriconazole with limited data for initial 2 week combination therapy with Echinocandin [AmphoB] for prolonged duration > 6-12 weeks)
When should we check Voriconazole levels at steady state ?
4-7 days
What can be used as secondary prophylaxis for treating invasive pulmonary aspergillosis ?
- Voriconazole
- Posaconazole
- *during subsequent immunosuppresion
What are some alternatives for secondary prophylaxis for treating invasive pulmonary aspergillosis?
- Itraconazole (unreliable bioavailability)
- Caspofungin
- Micafungin
What is blastomycosis?
-spore-forming mold, environmental exposure (inhalation) surrounding Ohio and Mississippi River, endemic in Manitoba, Ontario (LOTW)
What can blastomycosis cause?
Acute or chronic pulmonary infection (25-40% involve skin, osteoarticular, genitourinary or CNS), disseminated infection presenting 3-6 months post-exposure.
What is the treatment for moderate-severe blastomycosis ?
-AmphoB x 1-2 weeks, max 2 grams
THEN
-Itraconazole 200 mg po q12h x 6-12 months
What is the treatment for mild-moderate blastomycosis ?
Itraconazole 200mg po q12h x 6-12 months
Limited data for ______ as alternative to intraconazole
voriconazole
Describe mucormycosis
- spore-forming mold, environment exposure
- rhino-orbital-cerebral or pulmonary mucomycosis
- surgical treatment in conjunction with AmphoB [Posaconazole]
