Antifungal Therapy: New and Evolving Therapies

Yasmine Nivoix; Marie-Pierre Ledoux; Raoul Herbrecht

Disclosures

Semin Respir Crit Care Med. 2020;41(1):158-174. 

In This Article

Antifungal Strategies

Since the development of chemotherapy and immunomodulation-based therapies, improvements in patient outcomes in fields such as hematology, oncology, transplantation, and intensive care medicine have been tightly associated with the use of potentially life-threatening immunosuppression. While many advances have been made in the management of bacterial infections, invasive fungal diseases have remained a frequent cause of death in immunosuppressed patients, as the availability of effective and safe antifungal therapies has been limited. In the 1950s, the development of amphotericin B (AmB) in its deoxycholate formulation brought a major change to the overall prognosis of immunocompromised patients.[1] Nevertheless, toxicity limited its use, setting the stage for the development of other drugs that would be active, well-tolerated, and manageable with respect to drug–drug interactions, and would have complementary mechanisms of action (Figure 1). The currently available systemic antifungals are as follows:

Figure 1.

Antifungal drugs and their mechanism of action.

  • Polyenes: AmB deoxycholate (DAmB) and its lipid formulations.

  • Triazoles: fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole.

  • Echinocandins: caspofungin, micafungin, anidulafungin.

  • Allylamines: terbinafine.

  • Flucytosine.

Table 1 gives an overview of the spectra of current widely used antifungals. Although a more detailed description of each class will follow and indications for specific antifungals have been discussed in other articles of this issue, three additional tables are provided to summarize the main uses of these antifungals. We excluded from this review the agents used to treat Pneumocystis jirovecii infections as they do not belong to the antifungal class of agents.

Along with antifungal treatment, nondrug strategies should also be considered in the management of invasive mycoses. As proven in a large patient-level review, a critical point in improving the survival of patients with candidemia is the removal of central venous catheters.[2] Foreign bodies can form a sanctuary for fungi, where the activity of antifungals is nil. In quite a similar manner, a deep-seated infected site might be spared from the action of antifungals and might require surgical management as in, for instance, mucormycosis or aspergillosis.[3,4] Adjunctive maneuvers should also be considered with respect to fungal prophylaxis, depending on the depth of immunosuppression. For example, high-efficiency particulate air filtering for patients in deep and prolonged neutropenia is an additional step in preventing fungal infections.[5,6] This article aims to provide the reader with a synthesis of the relevant features of antifungal therapy impacting clinical use.

processing....