Antifungal Guideline

Antifungal Guidelines for Use in UMGCC
INDICATIONS
The use of amphotericin B deoxycholate, amphotericin lipid products, voriconazole, and caspofungin is
acceptable in the Cancer Center when used according to the following indications. For empiric and
curative treatment of fungal infections and the treatment of Aspergillus, patients are stratified into risk
groups:
Risk Classification
 Low risk – patients with expected duration of neutropenia < 7 days and who are not receiving high
dose corticosteroids.
 High risk – neutropenic patients with acute leukemia; all allogeneic and autologous bone marrow or
stem cell transplant recipients; any neutropenic patient with previously documented or clinically
suspected aspergillosis; a prolonged neutropenic prodrome before a diagnosis of cancer; neutropenic
patients receiving azole prophylaxis; any patient receiving high doses of corticosteroids
I. Empiric Therapy:
 Low risk neutropenic patients – need for empiric therapy should be assessed on a patient by
patient basis.
 Patients with acute leukemia – initial agents considered should be amphotericin B
deoxycholate 1mg/kg daily or amphotericin B lipid complex (ABLC) 5mg/kg/day.
 Bone Marrow Transplant patients
Autologous – initial agents considered should be amphotericin B deoxycholate 1mg/kg
daily or ABLC 5mg/kg/day.
Allogenic – initial treatment is ABLC 5mg/kg/day
All patients receiving any formulation of amphotericin B will be hydrated with saline before and
after amphotericin B dose to minimize renal toxicity. All patients receiving any formulation of
amphotericin B will be given pre-medications (e.g. acetaminophen 650 – 1000 mg,
diphenhydramine 25 mg intravenously (IV) or orally (PO), hydrocortisone 25 mg IV and/or
meperidine 25 mg IV) 30 minutes before amphotericin B infusion.
Leukemics and other patients with prolonged neutropenia should be switched routinely from
ABLC to oral voriconazole in the 5-7 days preceding expected bone marrow recovery if
• Suspected aspergillosis is well-controlled
• No diarrhea, emesis, or other condition exists that would prevent absorption of
voriconazole from the GI tract
II. Empiric Therapy for Patients Intolerant or Likely to be Intolerant of Amphotericin products
 The definitions of intolerance to an amphotericin B formulation are as follows:

 Infusion-related toxicities that persist 7 days after initiation of amphotericin despite use of
accepted pre-treatments given 30 minutes prior to infusion or with severe rigors and high
fevers. Patients receiving amphotericin B deoxycholate should be switched to ABLC.
Patients intolerant to ABLC should be switched to voriconazole (see below for dosing).
Patients who develop amphotericin B-related significant hypotension or infusion-related
respiratory distress should be switched to voriconazole immediately.
 Nephrotoxicity prior to or developing while receiving amphotericin B deoxycholate (serum
creatinine > 2 mg/dl in adults or > 1.5 mg/dl in children, doubling of serum creatinine, or an
estimated creatinine clearance < 50 ml/min) should be switched to ABLC. Any patient who
develops rapid increase in creatinine should be switched before creatinine > 2. Patients with
nephrotoxicity while receiving ABLC should be switched to voriconazole.
III. Curative therapy
Candida species:
Pending speciation by the microbiology laboratory, patients with invasive fungal infections should be
treated with an amphotericin B product because there is a high likelihood of fungal infection with C.
glabrata which is often resistant to fluconazole.
 Candida albicans – Fluconazole 400 mg daily, amphotericin B deoxycholate 0.6 mg/kg daily
or ABLC 3 mg/kg daily. Use of IV fluconazole and ABLC must be approved by the
Infectious Diseases service.
 C. tropicalis and C. parapsilosis – Fluconazole 800 mg daily, amphotericin B deoxycholate
1.0 mg/kg daily, ABLC 5 mg/kg daily, or caspofungin 70 mg first dose followed by 50
mg/day. Low dose flucytosine is indicated in selected patients. Use of IV fluconazole,
ABLC, and caspofungin must be approved by the Infectious Diseases service.
 C. glabrata – This fungus is increasingly amphotericin-tolerant in addition to fluconazole
resistant. Isolates should be sent for fluconazole susceptibility testing. Amphotericin B,
ABLC, high dose fluconazole, voriconazole, or caspofungin use should be considered in
consultation with Infectious Diseases. Doses are the same as for C. tropicalis and C.
parapsilosis treatment.
Aspergillosis:
 Amphotericin B deoxycholate 1 mg/kg daily IV

 ABLC 5 mg/kg daily IV
 Voriconazole dosing for proven (positive cultures or suggestive pathology), probable (chest CT
consistent with aspergillosis in proper clinical setting) or possible (negative chest CT in febrile
neutropenic patients) aspergillosis is 6 mg/kg q 12 hours for two doses followed by 4 mg/kg q 12
hours. Oral is the preferred route over intravenous administration for patients without diarrhea,
emesis, malabsorption, or severe mucositis.
 Caspofungin 70 mg daily IV. Caspofungin should be regarded as third-line therapy for
aspergillosis given anecdotal reports of caspofungin failure at UMMS and other institutions.
IV. Refractory therapy
 Refractory aspergillosis is defined as possible/probable/proven aspergillosis that has not responded

or has progressed after adequate curative therapy. Examples of refractory aspergillosis include:
Persistent fever or relapsed fever despite adequate antibacterial and antifungal antibiotics
Progressive pneumonia symptoms and/or worsened chest CT changes
Dissemination
 Patients who have failed amphotericin products should be switched to voriconazole 6 mg/kg q 12
hours. Patients with refractory aspergillosis should not be given amphotericin lipid doses greater
than 5 mg/kg/day without consultation with Infectious Diseases. Patients refractory to ABLC will
not be switched to Ambisome since there is no evidence that any amphotericin preparation is more
effective than any other.
 Although appealing at some level, there is no evidence that combination therapy of two
antifungals is more effective than a single agent.
V. Prophylactic therapy
Three studies have shown that prophylaxis with fluconazole reduces fungal-related mortality only in
allogeneic transplant recipients. Routine azole prophylaxis should not be given to leukemia patients
or to autologous transplant recipients. Allogeneic transplant recipients should receive oral
fluconazole 400 mg/day or oral voriconazole 200 mg twice daily for the first six months post-
transplant.

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Antifungal Guidelines for Use in UMGCC

 The definitions of intolerance to an amphotericin B formulation are as follows:

 Amphotericin B deoxycholate 1 mg/kg daily IV

IV. Refractory therapy

 Refractory aspergillosis is defined as possible/probable/proven aspergillosis that has not responded

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