Introduction
Systemic fungal infections represent an emerging problem in current
clinical practice. In Brazil, it is rare and difficult to obtain
statistical data on the incidence rates of such infections. What is
known are the causes that contribute to the increase in this rate. The
intensive use of broad-spectrum antibiotics, conditions associated with
immunosuppression (transplantation, cancer, chemotherapy treatment, and
Acquired Immunodeficiency Syndrome) and currently, in a pandemic
context, severe cases of COVID19. All of this has contributed to the
increase in invasive fungal infections and to the emergence of outbreaks
of infections across the country. It is estimated that nearly 4 million
people must have fungal infections in Brazil each year7.
One of the main concerns regarding the rational use of medications is
related to the use of antibacterials, which often leave antifungal
agents in the background of control. However, the increase in resistance
to various agents is a global reality and causes difficulties in the
therapeutic management of these infections, in addition to contributing
to the increase in treatment costs in the public and private health
system. In developing countries, few resources are used in actions
related to the rational use of antifungals. Furthermore, there are
limited data on the use of these agents in hospitals, and the Brazilian
scenario is no different21.
In this context, antimicrobials are among the groups of drugs most used
in the hospital environment, with the aim of reducing nosocomial
infection rates, but their excessive use can lead to the emergence of
resistant strains. Antifungals in this aspect are highlighted, as they
are drugs used in the treatment of fungal infections in many public
hospitals3.
The study of antifungal consumption in public hospitals is a
pharmaco-epidemiological practice, developed and based on studies of
drug use. This practice gained uniformity and internationalization with
the creation and implementation of the Anatomical-Therapeutic-Chemical
classification system and defined daily dose - ATC/DDD (Anatomical
Therapeutic Chemical/Defined Daily Dose), a tool that categorizes drugs
according to the acting sites. This made it possible to standardize the
studies in such a way that without this information previously defined
and outlined, it would not be possible to conceive or study the
consumption and consumption trend of this type of medicine in Heath
institutions23, 1.
Therefore, studies on the use of these drugs become important to draw a
profile of their use in different contexts, with a view to promoting
rational use and measuring hospital costs. For, a significant increase
in use implies higher costs 17, 1.
Thus, the trend study can be used to understand how drug consumption
varies over a given period, in order to manage care practices and
protocols, whether in national or international institutions, as well as
to make comparisons between hospital units and establish parameter and
usage reference18.
Therefore, studying, knowing and measuring data on the temporal
evolution of antifungal consumption, over 12 years in an adult Intensive
Care Unit (ICU), in a University Hospital, in Salvador-Bahia, gains even
more importance within the patient safety context and rational use of
medications. In this intensive care environment, hospital costs are
higher, adverse reactions and drug interactions are potentially more
frequent. Therefore, factors such as these, which directly influence
patient care, must be monitored with accurate information, to infer
measures and strategies, in the management of these drugs, in costs, in
the management and monitoring of therapy with a focus on rational
use18, 17, 1.
Within the pharmacological universe, there are many antifungal agents
that are divided according to their origin and can be natural or
synthetic. Natural drugs are polyenes and echinocandins; the synthetic
ones are represented by the azoles (Fluconazole, Voriconazole and
Itraconazole)10 .
They are drugs for systemic use,
which differ according to their chemical structure. Ketoconazole and
miconazole belong to the group of imidazoles; fluconazole, itraconazole
and voriconazole to the triazole group. The azoles act on the fungal
cytochrome P450 enzymes, inhibiting the demethylation of C-14α from
lanosterol, resulting in the accumulation of C-14α methylsterols and
decreasing the concentration of ergosterol. Thus, the cell membrane of
the fungus cannot be maintained, due to lower ergosterol production10, 11, 13.
Among the Azoles, the highlight is for the triazoles, which is a
pharmacological group with an excellent safety profile, used in the
treatment of invasive fungal infections. Since 1979, several newer
azoles (the triazoles) have been commercialized 10.
Fluconazole, one of the most commonly used antifungal agents, was the
first antifungal of a new subclass of synthetic triazole antifungals,
developed by the Pfizer® laboratory in Sandwich, England, in 1970, being
approved by the Food and Drugs Administration (FDA) and introduced in
the United States of America (USA), in 1990 under the name of
Diflucan24, 3.
All azoles are lipophilic and can be administered orally, with
satisfactory bioavailability. Itraconazole is highly protein bound and
therefore achieves high concentrations in adipose tissue and low
concentrations in Cerebrospinal Fluid (CSF). Fluconazole and
voriconazole are minimally protein bound (voriconazole >
fluconazole) and therefore can reach high concentrations in the CSF.
With the exception of fluconazole, which is metabolized and excreted
almost unchanged in the urine, all azoles are metabolized by the
liver14.
Fluconazole has excellent in vitro activity against Candida albicans and
is also effective against some non-albicans species such as C.
parapsilosis , C. tropicalis and C. glabrata, although
high doses of the drug are required for these species. Itraconazole is a
broad-spectrum triazole antifungal agent with antiangiogenic properties,
indicated for the treatment of endemic mycoses (histoplasmosis,
coccidioidomycosis, blastomycosis, onychomycosis) and for rescue
treatment for aspergillosis. It has variable bioavailability, with
significant differences between capsule and solution formulations, as
well as fasting versus feeding administration. The efficacy of
itraconazole was associated with the drug’s serum concentrations and due
to its erratic absorption, therapeutic monitoring is recommended4, 5.