Caspofungin: an overview

The echinocandins are a novel class of antifungal agents that have come into use over the past 10 years. The mechanism of action of these lipopeptide agents is via noncompetitive inhibition of the synthesis of 1,3-β-glucans, which are fungal cell wall constituents. All agents of this class are only available in an intravenous formulation. The first approved agent of this class was caspofungin (Cancidas^®). Caspofungin is a therapeutic option for patients with candidal esophagitis and deep-seated candidal infections, and is an alternative therapy for Aspergillus infections, especially in the salvage setting. In addition, it is a therapeutic option for the empiric therapy of febrile neutropenia. The usefulness of this agent in treating less common fungal infections has been cited in anecdotal reports. One major limitation of this drug is the lack of an oral formulation. Caspofungin may be considered as a component of combination antifungal regimens. Caspofungin represents a significant advance in the care of patients with serious fungal infections.     

Pharmacological advances in the treatment of invasive candidiasis

Invasive candidiasis is a common nosocomial infection, especially among the critically ill and immunocompromised patient populations. The recent standardization and increasing availability of antifungal susceptibility testing has the potential to optimize the selection of antifungal therapy. Treatment has been revolutionized in recent years with the marketing of several antifungal agents with excellent activity against Candida spp. These agents include the triazoles, fluconazole and voriconazole, and the echinocandin antifungals. While more expensive by acquisition cost, these newer agents are less toxic than the previously used drugs, and the triazoles offer the additional benefit of oral administration. The availability of new agents, future adoption of diagnostic tests for candidiasis, and susceptibility testing will have a major impact in the management of invasive candidiasis.     

Endogenous Candida endophthalmitis

Intraocular Candida infections, although uncommon, represent an important clinical problem owing to the potential for visual loss, which can be bilateral. Candida chorioretinitis and endophthalmitis are complications of systemic candidiasis with extension of the fungal pathogens to the uvea and retina. Early diagnosis and prompt management significantly affect the visual prognosis for these patients. This review evaluates the current literature on Candida endophthalmitis and includes discussion on presentation, diagnosis and management strategies. New systemic and intravitreal antifungal agents are also reviewed in the context of the management of intraocular fungal infection.     

Caspofungin: pharmacology,safety and therapeutic potential in superficial and invasive fungal infections

Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-β-D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad-spectrum antifungal activity against Candida and Aspergillus spp. without cross-resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida spp. and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the cytochrome P450 (CYP) enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients.     

Fungal infections in solid organ transplantation

Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following transplantation are relatively common due to the transplant recipients overall immunosuppressed status. The incidence of invasive mycoses following solid organ transplant ranges from 5 to 42% depending on the organ transplanted. These mycoses are associated with high overall mortality rates. Candida and Aspergillus spp. produce most of these infections. This article will review the risk factors, clinical presentation and treatment of invasive fungal infections in solid organ transplant patients, and evaluate the role of prophylactic therapy in this group of patients.     

Clinical pharmacology of antifungal agents in pediatric patients

Invasive fungal infections have emerged as important causes of morbidity and mortality in profoundly immunocompromised children including cancer, transplant and intensive care unit patients. Present treatment strategies for these infections are limited by toxicity, drug interactions and expense. In order to overcome these limitations, new antifungal compounds are being developed, which may improve the therapeutic armamentarium for prevention and treatment of invasive mycoses in high-risk children. This article summarizes the clinical pharmacology of established and newly developed antifungal agents, including new triazoles and echinocandins in pediatric age groups.     

Economic evaluation of the prevention and management of systemic fungal infections in neutropenic patients

Systemic fungal infections in neutropenic patients remain a clinical problem that is associated with morbidity and mortality. Continuing efforts are being made to develop improved (i.e., more effective or safe) drugs, and several new treatments have recently become available. These have increased the therapeutic options available to clinicians to address the problem of systemic fungal infections. Therapeutic choices are difficult when taking into account aspects of efficacy, safety and costs that are associated with the available alternatives. This review summarises the present status of health economic knowledge of the standard therapies that have been available for many years, and also reports on the most recent health economic evidence available for the newly developed treatment alternatives.     

卡泊芬净联合治疗急性红白血病并发卡氏肺孢子虫肺炎1例

肺孢子虫肺炎(PCP)是由卡氏肺孢子虫(现称卡氏肺孢子菌或伊氏肺孢子菌)所致的一种机会性感染,其临床表现缺乏特异性,疾病进展快,死亡率高,给临床诊断及治疗带来困难。新型抗真菌药卡泊芬净毒性小,耐受好,成为复方磺胺甲基异噁唑治疗PCP失败或不能耐受者的选择。本文报道卡泊芬净联合治疗1例急性红白血病伴发PCP患者,以期为PCP的治疗提供相关临床经验。     

Acremonium sclerotigenum-Acremonium egyptiacum: a multi-resistant fungal pathogen complicating the course of aplastic anaemia

A patient with aplastic anaemia, successively treated with caspofungin then liposomal amphotericin, developed a disseminated infection due to Acremonium, further confirmed as resistant in vitro to these drugs. Successful treatment was achieved with voriconazole. Multiple antifungal treatments may expose to the risk of breakthrough of multi-resistant pathogens in haematology patients.