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Nucci M
Rev Bras Hematol Hemoter. 2012;34(5):383-91
treatment for candidemia (caspofungin 70 mg on day 1 and 50 mg
thereafter; micafungin 100 mg daily or anidulafungin 200 mg on
day 1 and 100 mg thereafter). Step-down therapy to fluconazole
(400 mg once a day) after a few days of intravenous echinocandin
is a good alternative, provided that the patient is improving and
the isolate is not
C. glabrata
or
C. krusei
. An alternative to an
echinocandin is L-AMB (3 mg/kg daily). Catheter management
should be individualized, considering that in the majority
of cases of candidemia, the gut is the origin of infection
(64)
. A
reasonable approach is to start therapy with an echinocandin
or L-AMB and re-evaluate after 3-4 days of therapy
(65)
, unless
clinical signs of tunnel infection are clearly evident. In these
circumstances, prompt removal of the catheter is advised. For the
treatment of chronic disseminated candidiasis, L-AMB followed
by oral fluconazole or voriconazole for prolonged periods is the
treatment of choice. The use of corticosteroids may accelerate
clinical improvement
(66,67)
.
Aspergillosis
The drug of choice for primary treatment of invasive
aspergillosis is voriconazole
(23)
. Treatment usually is started with
the intravenous preparation (6 mg/kg twice a day on day 1 and
4 mg/kg thereafter), although a study suggested that starting
therapy with oral voriconazole is not associated with poorer
outcomes
(68)
. A recent study suggested that higher doses of oral
voriconazole (300 to 400 mg twice a day) are needed in order to
achieve therapeutic serum levels of the drug
(27)
.
An alternative to voriconazole is L-AMB. Although a
head to head comparison between L-AMB and voriconazole
has not been performed, response rates and survival of patients
treated with two doses of L-AMB (3 vs. 10 mg/kg daily)
(7)
were
comparable to those obtained in the voriconazole trial
(23)
.
A recent randomized study compared voriconazole with the
combination of voriconazole and anidulafungin in the treatment
of invasive aspergillosis
(42)
. The 6-week survival was 80.7% in
patients receiving combination therapy and 72.5% in patients
receiving voriconazole (p-value = 0.08). A sub-group analysis of
patients with baseline positive serum galactomannan showed a
statistically significant survival advantage of the combination arm.
Fusariosis
The outcome of invasive fusariosis is very poor, with a
21% 90-day probability of survival in patients with hematologic
diseases
(11)
and only 13% in HSCT recipients
(69)
. The drug of
choice is a lipid formulation of AMB. We recently analyzed the
outcome of 158 cases of fusariosis, and observed that the outcome
has improved in the last decade. Multivariate analysis showed
that receipt of d-AMB was associated with poor outcome. By
contrast, survival was improved with the use of voriconazole
(data in preparation for publication).
Mucormycosis
The recommended treatment of mucormycosis is a lipid
preparation of AMB. Although strong data regarding the dose are
lacking, some experts recommend higher doses
(12)
. Posaconazole
is also active against some agents of mucormycosis, and may
be used as step-down therapy once patient is responding to
intravenous AMB.
Conclusion
Hematologic patients are at risk of IFD, and therefore
antifungal agents are an important part of the therapeutic
armamentarium of any hematology unit. The hematologist
must be familiar with the epidemiology, diagnostic tools and
strategies of antifungal use. In addition, basic knowledge about
the pharmacologic proprieties of the different antifungal agents
is critical in order to best use these agents. This includes the
antifungal spectrum of the agents, doses, side effects and drug
interactions that may compromise the management of infection
and the underlying hematologic disease.
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