Treatment and prophylaxis of invasive candidiasis with anidulafungin, caspofungin and micafungin and its impact on use and costs - review of the literature

Abstract

Invasive fungal infections are on the rise. Echinocandins are a relatively new class of antifungal drugs that act by inhibition of a key enzyme necessary for integrity of the fungal cell wall. Currently there are three available agents: caspofungin, micafungin and anidulafungin.While the individual echinocandin antifungals have a different spectrum of licensed indications, basically all of them are available for the treatment of candidemia and invasive candidiasis. Antifungal treatment modalities basically include in therapy for suspected or proven infection and prophylaxis. All three drugs are comparatively expensive. Therefore a systematic review of the literature was performed to investigate the following aspects:• General aspects of cost-effectiveness in the treatment of invasive fungal infections• Cost-effectiveness of the treatment with the above-mentioned antifungals• Cost-effectiveness in two settings: therapy and prophylaxisEarly initiation of antifungal therapy, adjustment after availability of microbiological results, duration of therapy, success and occurrence of severe complications (e.g renal failure) are the most important cost drivers in antifungal therapy.Considering the specific antifungals, for caspofungin the best evidence for cost-effectiveness is found in treatment of invasive candidiasis and in empiric therapy of suspected infections. Favourable economic data are available for micafungin as a cost-effective alternative to LAmB for prophylaxis in patients with hematopoietic stem cell transplantation (HSCT). For anidulafungin, cost-effectiveness was demostrated in a pharmacoeconomic model. Net savings - yet not significant - were observed in a retrospective chart review of 234 patients. Generally, however, most analyses are still based on pharmacoeconomic modelling rather than direct analysis of trial data or real-life clinical populations.As an overall conclusion, using caspofungin, micafungin, or anidulafungin is not more expensive than using other established therapies. Micafungin has proven to be cost-effective in prophylaxis if the local fungal epidemiology indicates a high level of resistance to fluconazole. Switch strategies involving early initiation of broadly active therapy with switch to cheaper alternatives according to microbiology results and clinical status and early initiation of an appropriate therapy have been proven to be cost-efficient independent of the antifungal agent.

Treatment of invasive candidiasis: between guidelines and daily clinical practice

“…However, a timely start of a broad-spectrum antifungal with fungicidal and anti-biofilm activity, switching to a cheaper alternative according to microbiology results and clinical status is considered to be the main determinant of cost-effectiveness, regardless of the antifungal agent [37].…”

In-vitro Inhibition of Biofilm Formation in Candida albicans and Candida tropicalis by Heat Stable Compounds in Culture Filtrate of Aspergillus flavus

“…Of all candidemia cases, about 35-50% cases of bloodstream infection occur in the ICU setting with high attributable mortality [15]. Treatment of this disease is very challenging due to formation of complex structured communities called biofilms in 20-70% cases that retard drug diffusion and protect the fungus from host immune defenses, and toxicity of the antifungal drugs administered [16,4,5]. For example, Amphotericin B is an effective antifungal to treat candidemia but can be nephrotoxic in up to 80% cases [17].…”

“…Treating biofilm-associated invasive candidiasis is very difficult in developing countries since drugs available are prohibitively costly and have their own adverse effects [4]. Also, drug penetration through fungal biofilms is diminished due to formation of a reaction-diffusion barrier [4,5]. In addition, increase in cases of candidemia due to species other than Candida albicans and growing resistance to azole antifungal compounds have aggravated the problem [6].…”

“…This disease entity is associated with the formation of structured, complex microbial communities known as biofilms [3]. Treating biofilm-associated invasive candidiasis is very difficult in developing countries since drugs available are prohibitively costly and have their own adverse effects [4]. Also, drug penetration through fungal biofilms is diminished due to formation of a reaction-diffusion barrier [4,5].…”

A substituted sulfonamide and its Co (II), Cu (II), and Zn (II) complexes as potential antifungal agents

“…Invasive fungal infections constitute an ever-increasing cause of morbidity and mortality among immunocompromised individuals, those who have undergone intra-abdominal surgery, neonates, and the elderly 17 . While fluconazole remains an important agent for the treatment of Candida and other yeasts infections, the introduction of other triazoles active against yeasts and molds, such as posaconazole, and voriconazole, or drugs belonging to other classes, such as echinocandin, anidulafungin, caspofungin, and micafungin, has increased the options for prophylaxis, and therapy of many fungal infections 18,19 .…”