Antifungal Treatment without Compromise

George KARAM.

Author address: 

Louisiana State University Sckwol of Medicine, New Orleans, Louisiana, USA

Abstract: 

A challenge in clinical medicine is to achieve an optimal degree of efficacy without compromising safety or cost effectiveness. This mandate transcends the management of bacterial infections and also applies to fungal infections. In hospitalized patients, two invasivc fungal pathogens are the most noteworthy: Camiida and Aspergillus. The classic patients in whom invasive aspeigillosis develops are those who are immunocompromised on the basis of either neutropenia or depressed cell mediated immunity. The overall clinical response rates of treating aspergillosis in these patient populations have ranged from 32% to 57%. Once patients fail initial therapy and require salvage treatment, response rates are generally 30% or less. The eclfinocandin class of antifungal drugs represents the newest antifungal agents to be clinically available for invasivc fungal infections, and easpofungin is the first available agent in this class. In clinical trials as well as in a compassionate use program for the treatment of patients who had either failed or were intolerant of amphotericin, caspofungin had overall response rates of about 45%, which was at bast coropaz-able to the published medical literature for clinical response in patients receiving initial therapy for aspergiUosis, and better than previous reports of salvage therapy. As Candida infections have evolved in clinical practice, patient populations infected with this pathogen include not only those immuno compromised on the basis of defects in neutropliil function or cell-mediated immunity but also non-immunocompromised patients with risk factors for invasive candidal infections, including candidemia. The noteworthy trend in eandidal infections is the increasing trend toward infection caused by non albicans species of Catwlida. Like amphotcfiein B but in contrast to the presently available azoles, caspofungin is fungicidal against Catwlida isolates and is piedictably active against the non-albicans species, including those that are azole ~esistant. These properties assist the clinician in understanding the findings of the clinical trial that compared caspofungin to amphotericin B in the treatment of patients with invasive eandidiasis (in which the majority of those evaluated had candidemia) and demonstrated similar efficacy. A major observation of this trial was that caspofungin was in a statistically significant way less likely to cause adverse clinical events, laboratmy abnm'malities, nephrotoxicity, or withdrawal due to adverse effects. Analyses published in peer-ieviewed journals have noted that preventing nephrotoxicity and piecluding the attendant costs associated with the treatment of this complication may make using caspofungin a more cost effective treatment choice than amphotcfiein B in certain patient populations. Since neutropenic patients are at risk of infection with Camiida and Aspergillus, a challenge over the years has been to treat both pathogens with a single agent in febiile, neutropenic patients who do not respond to amibactgrial therapy. In the largest trial to date of empiric therapy in patients with persistent fever and neutropenia, easpofungin was compared to liposomal amphotericin B (J~ AmB). Overall, easpofungin was as effective as LAmB as empiric therapy of suspected fungal infection in this patient population. In patients who had baseline fungal infection (defined as infections present on or befme day 2 of the study), caspofungin in a statistically significant manner was superior to L-AraB both in clinical efficacy and in survival. Caspofungin was better tolerated than LAmB, with significantly lower rates of nephrotoxieity, infusion related events, drug related adverse effects, and discontinuation of therapy due to drug-ielated adverse effects. Because invasive fungal infections are common in immunocompromised patients who may be on multiple medications, including those that prevent transplant rejection, drug interactions are important to consider in the selection of antifungal therapy. In contrast to certain antifungal agents that inhibit the cytoehrome P450 enzyme system and therefore potentially lead to drug-drug interactions, caspofungin is not an inhibitor of any enzymes in the cytocl~'ome P450 system and may not substantially interact with antliejection drugs, other antifungal agents, or dfampin. Elimination of such interactions is an important consideration in a patient population already at risk of problems based on underlying disease and the multiple drugs required for their management. Because of the potentially life-threatening infections that are caused by Camiida and Aspergillus, it is important for the cliniciml to have efficacious therapy that minimizes adverse effects, piecludes significant drug-drug interactions, and offers cost effectiveness. The published literature and clinical experience support the role of caspofungin as such an agent.
2005

abstract No: 

ISSl.2

Full conference title: 

International Congress on Chemotherapy, 24th Meeting
    • ICC 24 th