Candida and parasitic infection: Helminths, trichomoniasis, lice, scabies, and malaria
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Treatment of Candida vulvovaginitis in pregnancy is typically limited to topical azoles and nystatin (16,25). For many years, nystatin was the primary drug used for Candida vulvovaginitis in pregnancy because its extremely poor absorption was felt to improve its safety (pregnancy category B) (25). As studies have proven, the increased efficacy of the azole antifungal agents, miconazole, clotrimazole, butoconazole, and terconazole, has become the mainstays of therapy in pregnancy. They have been used extensively in human pregnancy with no adverse effects or increase in congenital malformations noted, but most remain pregnancy category C due to the absence of adequate controlled human studies. There is no clear leader from this group in terms of efficacy and patient satisfaction, so selection may be based on availability and cost. Seven-day treatment is usually needed in pregnancy due to the higher rates of treatment failure and recurrence. Cure rates are typically 5% to 10% lower than those in nonpregnant women for the same dosing regimen.
Pharmacology of azole antifungal agents
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
The key structural component of all members of the azole class is the 5-membered azole ring (Figure 12.1). The imidazoles contain 2 nitrogen atoms in this ring, while the triazoles incorporate a third nitrogen into this structure. Many triazoles are derived from earlier members of the imidazole class such as itraconazole and posaconazole, which are structurally similar to the long lipophilic molecule—ketoconazole. This is in contrast to fluconazole that is less lipophilic and has a smaller molecular size that is more akin to the structures of clotrimazole and similarly appearing imidazoles. Although more lipophilic than fluconazole, voriconazole most closely resembles the structure of fluconazole [1]. The newest azole antifungal, isavuconazole, is most structurally similar to voriconazole [2].
Fungal Infections
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Overall, there are four main classes of antifungal treatments: azoles, polyenes, nucleoside analogues and echinocandins. Azoles are synthetic agents that block the synthesis of ergosterol, an essential component of fungal plasma membranes. Clotrimazole is one of the most widely used azoles in otomycosis and is highly effective, with efficacy rates of between 95% and 100%.15 Other azoles that are widely used include fluconazole, ketoconazole and miconazole. Polyenes, such as nystatin, are thought to interact with sterols in the fungal plasma membrane, causing pores to form within the membrane, thus causing altered permeability and fungal death.16 Although nystatin is not available as an otic preparation it can be prepared as a solution or suspension, or applied as a cream, ointment or powder. Amphotericin B, another polyene antifungal agent, is used in severe, life-threatening infections, such as fungal malignant otitis externa. Nucleoside analogues, such as flucytosine, interfere with fungal DNA, RNA and protein synthesis. Flucytosine has a reported efficacy of 90% and is available as an ointment.
Miconazole for the treatment of vulvovaginal candidiasis. In vitro, in vivo and clinical results. Review of the literature
Published in Journal of Obstetrics and Gynaecology, 2023
Pedro Antonio Regidor, Manopchai Thamkhantho, Chenchit Chayachinda, Santiago Palacios
Miconazole has multiple mechanisms of action. Azoles, the most common antimycotics in the pharmacopeia, damage fungal organisms by interfering with ergosterol biosynthesis, which results in toxic methylated sterol levels (Vanden Bossche et al.1990). Kobayashi et al. described an additional antifungal mechanism for miconazole: accumulation of drug-induced reactive oxygen species (ROS) within the fungal organism results in oxidative damage and cell death (Kobayashi et al.2002). This mechanism was confirmed in another publication by Thevissen et al. who studied the effects of miconazole in Saccharomyces cerevisiae and C. albicans demonstrated that the antifungal increases the stability of actin cables which corresponds to the model that an enhanced stability of actin filaments followed by clumping of actin triggers generation of ROS and induces apoptosis in yeast cells (Thevissen et al.2007). In addition, miconazole increases intracellular ROS partly through inhibition of fungal catalase and peroxidase. It can be assumed that ROS-induced apoptosis is probably the basis for the fungicidal activity of miconazole, whereas other azoles are fungistatic. It could be further demonstrated that only miconazole but no other imidazole’s are able to induce ROS in C. albicans (Francois et al.2006).
Clinical Features, Risk Factors, and Management of Candida Keratitis
Published in Ocular Immunology and Inflammation, 2023
Ahmad Masoumi, Mohammad Soleimani, Momeneh Azizkhani, Alireza Izadi, Kasra Cheraqpour, Seyed Ali Tabatabaei, Sadegh Khodavaisy, Mehdi Aminzadeh
Unfortunately, some topical medications currently used to treat fungal keratitis do not penetrate well into the corneal stroma. Intrastromal and intracameral injections of antifungal drugs may circumvent this problem, especially in cases of deep infiltration, significant anterior chamber reaction, or lack of response to conventional topical and systemic treatment.16 Eight eyes with Candida keratitis underwent intrastromal injection of amphotericin B or voriconazole. Azoles are commonly prescribed to treat fungal infections. Widespread use of fluconazole for prophylaxis against Candida infections is believed to have led to increased resistance to this antifungal agent. Of note, in vitro susceptibility of Candida spp. is found to be less for fluconazole compared to itraconazole, voriconazole, amphotericin B, and caspofungin.
Risk of fetal malformation, spontaneous abortion, and adverse pregnancy outcomes after gestational terbinafine exposure: a systematic review
Published in Journal of Dermatological Treatment, 2022
Philipp Foessleitner, Alex Farr, Julia Deinsberger
When a fungal infection is diagnosed during pregnancy, it is important to identify the appropriate antifungal treatment. Topical azoles, including fluconazole, itraconazole, and clotrimazole, are recommended as first-line therapy during pregnancy (21–23). In cases of severe symptoms, recurrence, or when topical therapy fails, oral azoles are recommended in non-pregnant patients (21). However, the safety of oral azoles during pregnancy is controversial. Recent meta-analyses regarding this topic found an increased likelihood of heart and limb malformations and spontaneous abortion after gestational exposure to oral fluconazole (24,25). Additionally, oral itraconazole use during pregnancy was associated with an increased risk of eye defects (25). Furthermore, these agents have the ability to disrupt estrogen and testosterone synthesis, although it remains unclear if fetal corticosteroid synthesis is affected (10). Griseofulvin, another antifungal agent was shown be have teratogenic effects in animals; however, data on humans are limited (26). In light of these findings, terbinafine could offer a safe alternative as antifungal treatment during gestation.
Related Knowledge Centers
- Aromaticity
- Biomolecule
- Heteroatom
- Imidazole
- Oxygen
- Pyrrolidine
- Sulfur
- Nitrogen
- Hantzsch–Widman Nomenclature
- Redox