Conventional Antifungals for Invasive Infections Delivered by Unconventional Methods; Aerosols, Irrigants, Directed Injections and Impregnated Cement

Abstract

The administration of approved antifungals via unapproved formulations or administration routes (such as aerosol, direct injection, irrigation, topical formulation and antifungal-impregnated orthopedic beads or cement) may be resorted to in an attempt to optimize drug exposure while minimizing toxicities and/or drug interactions associated with conventional (systemic) administrations. Existing data regarding such administrations are mostly restricted to uncontrolled case reports of patients with diseases refractory to conventional therapies. Attribution of efficacy and tolerability is most often problematic. This review updates prior published summaries, reflecting the most recent data and its application by available prevention and treatment guidelines for invasive fungal infections. Of the various dosage forms and antifungals, perhaps none is more widely reported than the application of amphotericin B-containing aerosols for the prevention of invasive mold infections (notably Aspergillus spp.).

Resistance profiles to antifungal agents in Candida albicans isolated from human oral cavities: systematic review and meta-analysis

“…The authors also indicated that the results might be influenced by the reduced number of studies included, the differences in patient age, the dosage, the course, and the frequency of drug administration [ 34 ]. Drew and Perfect emphasized that published data regarding the administration of antifungals by alternative routes are scarce and restricted to uncontrolled case reports or studies with small sample sizes [ 35 ]. Fitchenbaum et al reported that in a group of patients with HIV infection or CDC-defined AIDS, amphotericin B oral suspension had limited efficacy for treating fluconazole-refractory oral candidiasis.…”

Emergence of Advanced Antifungal-Delivery Approaches for the Treatment of Tinea Pedis

“…They are simple to use and almost immediately absorbed by the skin. Tinea pedis on the soles of the feet is frequently treated using sprays [11].…”

“…Powders are applied to body parts where moisture is a problem, like the space between the toes. Usually, they are used after washing and drying the impacted region [11].…”

“…For the treatment of skin-related fungal infections, numerous researches utilizing niosomal formulation have been conducted. To improve its skin penetration, Alomrani et al Tween 85 with tri-alkyl chain, and moderate HLB (11), was also assessed. According to the study's findings, all niosomes had significantly higher antifungal activity than the ITZ solution [17].…”

Relapsing Aspergillus otomycosis despite prolonged systemic antifungal therapy and resolution after topical voriconazole administration: A case report

“…While favourable outcomes have been reported in the literature with usage of oral voriconazole for Aspergillus otomycosis [ 3 , 4 ], systemic antifungal treatment is often utilised only after topical therapy has failed, due to concerns of tolerability and side effects. Topical voriconazole has been utilised in case reports as an alternative option for treating refractory otomycosis failing to respond to usual therapeutic options [ 5 , 6 ]; though otic administration of topical voriconazole is not a conventional mode of drug delivery, and at present is not licensed for such use [ 7 ]. We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy.…”