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Review Article
383
Rev Bras Hematol Hemoter. 2012;34(5):383-91
Use of antifungal drugs in hematology
Marcio Nucci
Universidade Federal do Rio de Janeiro -
UFRJ, Rio de Janeiro, RJ, Brazil
Conflict-of-interest disclosure:
The author declares no competing financial
interest
Submitted: 7/19/2012
Accepted: 7/23/2012
Corresponding author:
Marcio Nucci
Hospital Universitário Clementino Fraga
Filho, Universidade Federal do Rio de Janeiro-
UFRJ
Rua Prof. Rodolpho Paulo Rocco 255
21941-913 Rio de Janeiro, Brazil
Phone/fax: +55 21-25622460
mnucci@hucff.ufrj.br
www.rbhh.org or www.scielo.br/rbhh
DOI: 10.5581/1516-8484.20120095
Introduction
Invasive fungal disease (IFD) represents a major complication in hematological patients.
These infections are particularly frequent in patients with hematological malignancies who
develop prolonged and severe neutropenia, such as patients with acute myeloid leukemia
(AML) and in hematopoietic stem cell transplant (HSCT) recipients
(1)
. The problem is
aggravated by the fact that most IFD are difficult to diagnose and because host factors are
key determinants of the outcome, resulting in a prognosis that is usually poor, especially if
immunodeficiency persists.
Antifungal agents are frequently used in hematologic patients for different purposes.
In neutropenic patients, antifungal agents may be used as prophylaxis (for at-risk patients),
as empiric therapy, or to treat an IFD that has been diagnosed. Empiric therapy refers to the
start of an antifungal agent provided to neutropenic patients with unexplained, persistent or
recurrent fever despite appropriate antibiotic therapy
(2)
. In addition to prophylaxis, empiric and
pathogen-directed antifungal therapy, a fourth modality of antifungal use has been recently
advanced, called preemptive or diagnostic-driven antifungal therapy
(3)
.
Antifungal drugs in hematology
The antifungal drugs frequently used in hematologic patients belong to the following
classes: the polyenes, the azoles, and the echinocandins. Tables 1 and 2 summarize the
pharmacologic characteristics and the spectrum of the antifungal agents. Among the polyenes,
deoxycholate amphotericin B (d-AMB) has been largely used in hematologic patients despite
severe and frequent side effects. However, with the availability of the lipid formulations and
other drug classes, its use does not seem justifiable in the hematology setting anymore, given
the complexity of these patients, who receive many concomitant nephrotoxic drugs such as
antineoplastic agents, immunosuppressants and anti-infective drugs. Attempts to decrease
d-AMB toxicity by adding lipid emulsions
(4)
or by administrating the drug by continuous
infusion
(5)
are not recommended because although its use may be associated with less acute
adverse events, the efficacy has not been proved.
There are three commercially available lipid formulations of amphotericin B: liposomal
amphotericin B (L-AMB), amphotericin B lipid complex (ABLC) and amphotericin B in
colloidal dispersion (ABCD). Data on head to head comparisons between the different lipid
formulations are generally not available, with the exception of a study of empiric therapy in
neutropenic patients that compared L-AMBwithABLC
(6)
. In this study, L-AMBwas associated
with fewer side effects, including renal toxicity. In general, the three lipid formulations are
less nephrotoxic than d-AMB, with the frequency of acute infusion-related adverse events
being the highest with ABLD, followed by d-AMB and ABLC, and L-AMB. Standard daily
doses of the lipid formulations are 3 mg/kg for L-AMB and 5 mg/kg for ABLC and ABCD.
Higher daily doses of L-AMB (10 mg/kg) did not show superiority over the 3 mg/kg dose
used in the treatment of IFD and was associated with more side effects
(7)
. Notwithstanding
Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are
frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents
may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has
been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of
antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the
principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where
these agents have been used.
Keywords:
Antifungal agents; Mycoses; Aspergillosis