Combination antifungal therapy : a strategy for the management of invasive fungal infections
Fecha
2014Autor
Carrillo Muñoz, Alfonso Javier
Finquelievich, Jorge Luis
Tur Tur, Cristina
Eraso, Elena
Jauregizar, Nerea
Quindós, Guillermo
Giusiano, Gustavo Emilio
Metadatos
Mostrar el registro completo del ítemResumen
Invasive mycoses have become an important public health
problem as their incidence has increased dramatically in the
last decades, while the discovery of the ideal antifungal agent
has not been yet obtained1-4. The population at risk for these
deadly mycoses includes patients with AIDS, transplant recip-
ients, patients with haematological malignancies and other
immunocompromised individuals, exposed to fungal patho-
gens4. Aetiology and epidemiological patterns of these inva-
sive mycoses are changing due to advances in medical man-
agement or healthcare practices, such as the introduction of
newer modalities for hematopoietic stem cell transplantation,
the improvements of organ transplantation practices, the use
of novel immunosuppressive agents and current antimicrobial
prophylactic strategies.
Although Candida albicans is the predominant causative
agent of invasive mycoses, other species of Candida, and dif-
ferent Aspergillus and Cryptococcus species are frequently in-
volved in infections affecting immunocompromised patients.
The role of other yeast-like organisms, such as Trichosporon,
Saprochaete or Malassezia and filamentous fungi, such as
Fusarium, Acremonium, Mucor, Rhizopus, Paecilomyces, Sce-
dosporium, Scopulariopsis brevicaulis, dermatophytes, dema-
tiaceous and dimorphic fungi as emerging pathogens in human
diseases is also important4-18. Moreover, classic species such as
C. parapsilosis, C. glabrata or A. fumigatus currently known
are complex of new cryptic species19. The use of highly active
antiretroviral therapy has resulted in a significant decrease in
the incidence of fungal opportunistic infections among per-
sons with AIDS who live in developed countries. However,
since the availability of highly active antiretroviral therapy is
quite limited in many developing countries with widely spread
HIV epidemics, fungal opportunistic infections such as oropharyngeal candidiasis, cryptococcosis, histoplasmosis or peni-
cilliosis are now an important cause of morbidity and mortality
for patients with AIDS. Advances in surgical techniques and in
immunosuppressive regimens have accounted for a decline in
the incidence of invasive candidiasis in organ transplant recip-
ients at high risk for Candida infections, but which has also re-
sulted in a rise in the frequency of non albicans Candida spe-
cies as pathogens. The increasing use of more aggressive im-
munosuppressive drugs in hematopoietic stem cell transplant
recipients has resulted in an increase in the incidence of in-
vasive filamentous mycoses (such as aspergillosis, fusariosis or
mucorales) among these patients4,5,7,9-12,14-16,20. Recent changes
in the epidemiology of invasive fungal infections are having
important implications in the management of these infections.
An early diagnosis of invasive mycoses is very important in or-
der to treat patients at a stage of the disease when the fungal
cell concentrations and body tissues damage burdens are low.
However, diagnosis is difficult and in many cases is not possi-
ble to obtain a reliable evidence of invasive mycosis21-23.
Against this problem, antifungal combination therapy is
one of the available management strategies to provide the
clinicians with effective tools. Also new potent generation of
new triazole derivative molecules; liposomal and other for-
mulations for delivering amphotericin B (AMB) or azole drugs;
and immunomodulators are available and also in the pipeline.
Nevertheless, some safety, toxicological, pharmacokinetic as-
pects or spectrum profile are not perfect for every drug. More-
over, the industry should develop newer families of antifungal
drugs, while combination therapy tends to maximize the po-
tency of known drugs and also of other substances combined
with antifungal drugs, without any antagonist mode of action,
in order to reduce clinical failure. The rationale for combina-
tion therapy is to maximize antifungal effects by attacking dif-
ferent fungal targets at the same time with additive or syner-
gistic effects, but some combinations offer good results when
using the same target. However, clinical studies are required to
provide a correlation with in vitro studies. This review has tried
to summarize the accumulated experience on the combination
of current antifungal agents used in the treatment of invasive
fungal infections.
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