Fluconazole and voriconazole are both triazole antifungal drugs that exert bactericidal effects by inhibiting cytochrome P450-mediated demethylation of 14α-sterols in fungi that prevent ergosterol biosynthesis. Due to its safe, efficient, and broad-spectrum properties, it is widely used in the treatment and prevention of deep fungal infections [1].
However, the chemical structure of the two is not the same. The chemical name of fluconazole is 2-(2,4-difluorophenyl)-1, 3-bis
-(1 H-1, 2, 4-三唑-1-基)-2-丙醇分子式：C13 H12F2N6O。 伏立康唑化学名称：（2R,3S）-2-（2,4-二氟苯基）-3-（5-氟基-4-嘧啶）-1-（1 H-1,2,4-三唑-1-基）-2-丁醇，分子式：C16 H14F3N5O。
Chemical structure of fluconazole (left) vs. voriconazole chemical structure (right)
It is precisely because of the difference in chemical structure that the antimicrobial spectrum of the two is significantly different. How to choose clinical antifungal therapy? Let's take a look!
1
The antimicrobial spectrum is different
Fluconazole has strong antibacterial activity against yeast-like bacteria, especially against Candida albicans and Cryptococcus neoformans, but is basically inactive against Candida glabrata and Candida kere. In addition to its significant effect on Aspergillus, voriconazole has good antibacterial activity against fluconazole-resistant Candida, Cryptococcus, Fusarium, and Histoplasma [1-2], as shown in Table 1:
Table 1 Comparison of antimicrobial activity of fluconazole versus voriconazole against common fungi [3]
Note: ++ is recommended, + is sensitive, ± is uncertain antimicrobial activity, 0 is not recommended, poor antimicrobial activity or natural resistance
2
Differences in clinical application
In recent years, there has been an increasing incidence of invasive fungal infections (IFDs) in mainland China, with Aspergillus, Cryptococcus, and Candida being the main pathogens, with the lungs being the most common target organ for IFD [1,4]. For mild Candida albicans and Cryptococcus neoformans infections, fluconazole is preferred; For Aspergillus infections, voriconazole is preferred. The specific recommendations are as follows:
Invasive aspergillosis (IA):
Aspergillus conidia can temporarily adhere to and inhabit the respiratory tract after inhalation, and if the inhalation amount is large or the body's immune function is impaired, it will germinate hyphae and cause morbidity. The lungs are the most common site of IA infection, with more than 75% of IA occurring in the lungs, and less commonly in the sinuses, central nervous system, and heart [5]. Aspergillus fumigatus is the most common pathogen causing IFD, and treatment options are shown in Table 2:
Table 2 Treatment options for invasive aspergillosis [1,4-6]
Cryptococcosis:
Cryptococcus can infect any tissues and organs of the human body, the most common site is the central nervous system, followed by the lungs and skin, but in recent years, the incidence of pulmonary cryptococcosis has been increasing year by year, and its treatment options are shown in Table 3:
Table 3 Treatment options for cryptococcosis [7-8]
Invasive candidiasis:
Candidemia is the most common clinical form of invasive candidiasis and often has a poor prognosis, while other types of infection include infections of the abdominal cavity, heart, intraocular, central, and pulmonary areas. Primary Candida pneumonia is relatively rare in clinical practice, and direct microscopic examination of lower respiratory tract specimens and isolated and cultured Candida cannot distinguish between colonization and infection, and has little clinical significance. Treatment options for invasive candidiasis are shown in Table 4:
Table 4 Treatment options for invasive candidiasis [1,4,9]
Treatment of mycosis of the lungs very common:
(1) Treatment of histoplasmosis: severe infections, including central nervous system infections, should be treated with amphotericin B initially, and mild to moderate infections should be treated with itraconazole. Fluconazole is less effective than itraconazole, and voriconazole and posaconazole are highly effective in H capsular histoplasmosis and are used as rescue therapy.
(2) Treatment of coccidioidomycosis: Antifungal therapy is not recommended for immunocompetent patients who are infected with coccidioidium for the first time and have no risk of dissemination. Fluconazole or treatment is preferred for patients at high risk of complications or disseminatence, and amphotericin B is the option for severe infections, followed by sequential treatment with fluconazole or itraconazole if the disease improves.
3
Adverse reactions and precautions of the two drugs
Fluconazole and voriconazole have high oral bioavailability, and the dose should be adjusted for patients with hepatic and renal insufficiency, as shown in Table 5:
Table 5 Adverse reactions and precautions of fluconazole and voriconazole
This article is transferred from: Lilac Garden Breathing Time