Caspofungin: a review of its use in the treatment of fungal infections

Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp.Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.     

Caspofungin: first approved agent in a new class of antifungals

Caspofungin (Cancidas, Merck & Co. Inc.) is the first echinocandin antifungal agent to gain FDA-approval for use in the US. It has excellent clinical activity against Candida spp. and Aspergillus spp. but lacks significant activity against Cryptococcus neoformans. Caspofungin may have some activity against dimorphic fungi such as Histoplasma capsulatum and Coccidioides immitis, but no clinical data is available for treatment of these infections. Caspofungin has demonstrated poor activity against most filamentous fungi in vitro. Several clinical trials have demonstrated its efficacy in the treatment of oropharyngeal, oesophageal and invasive candidiasis, as well as invasive aspergillosis. As a result of caspofungin's unique mechanism of action, and the high morbidity and mortality of invasive fungal infections, there is considerable interest in using this new antifungal agent as part of a combination antifungal therapy. In vitro studies and small case series indicate that caspofungin does not appear to be antagonistic when combined with other antifungals, such as itraconazole, voriconazole or amphotericin B against Aspergillus spp. Caspofungin exerts concentration-dependent killing effects in many different in vitro and animal models of disseminated fungal infection. The usual daily dose is 50 mg/day i.v. following a 70 mg i.v. loading dose. However, higher caspofungin doses have been safely administered and up to 70 mg/day can be administered for patients who fail to respond to lower doses. Caspofungin has an excellent safety profile with reduced toxicities, compared to other licensed antifungal agents. Fever, thrombophlebitis, headache and liver enzyme elevations were the most common drug-related side effects reported in clinical trials so far. Additional data are needed to document its safety in long-term use, and with higher doses in patients with invasive fungal infections. Caspofungin is a promising agent as first-line therapy for invasive candidiasis, and as salvage therapy for invasive aspergillosis. However, more clinical data are needed to define its role as primary therapy for invasive aspergillosis, and its role in combination antifungal therapy.     

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.     

Newer systemic antifungal agents : pharmacokinetics, safety and efficacy

The past few years have seen the advent of several new antifungal agents, including those of a new class and a new generation of an existing class. Caspofungin, the first available echinocandin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin had comparable efficacy to amphotericin B for candidaemia and invasive Candida infections. Caspofungin and two more recently introduced echinocandins, micafungin and anidulafungin, are available as intravenous formulations only and characterised by potent anti-candidal activity, as well as few adverse events and drug interactions. Voriconazole, the first available second-generation triazole, available in both intravenous and oral formulations, has added a new and improved therapeutic option for primary therapy of invasive aspergillosis and salvage therapy for yeasts and other moulds. In a randomised trial, voriconazole demonstrated superior efficacy and a survival benefit compared with amphotericin B followed by other licensed antifungal therapy. This and data from a noncomparative study led to voriconazole becoming a new standard of therapy for invasive aspergillosis. Voriconazole has several important safety issues, including visual adverse events, hepatic enzyme elevation and skin reactions, as well as a number of drug interactions. Posaconazole, only available orally and requiring dose administration four times daily, shows encouraging efficacy in difficult to treat infections due to zygomycetes. Ravuconazole, available in both intravenous and oral formulations, has broad-spectrum in vitro potency and in vivo efficacy against a wide range of fungal pathogens. Clinical studies are underway. Despite the advances offered with each of these drugs, the morbidity and mortality associated with invasive fungal infections remains unacceptable, especially for the most at-risk patients. For individuals with severe immunosuppression as a result of chemotherapy, graft-versus-host disease and its therapy, or transplantation, new drugs and strategies are greatly needed.     

Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis

Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal cell wall synthesis). Caspofungin (Cancidas), Caspofungin MSD) is the first echinocandin to be approved and is administered intravenously.Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole 200 mg/day and was at least as effective as intravenous amphotericin B 0.5 mg/kg/day in patients with oesophageal candidiasis in two randomised, double-blind studies. A favourable combined clinical and endoscopic response occurred in 81% of caspofungin recipients versus 85% of fluconazole recipients and in 74% of caspofungin recipients versus 63% of amphotericin B recipients. A favourable combined response rate of approximate, equals 90% and approximate, equals 60% occurred in the stratum of patients with oesophageal candidiasis who received caspofungin or amphotericin B in a third randomised, double-blind study.Caspofungin (70 mg loading dose followed by 50 mg/day) had similar efficacy to intravenous amphotericin B (0.7-1.0 mg/kg/day in patients with neutropenia and 0.6-0.7 mg/kg/day in patients without neutropenia) in patients with invasive candidiasis in a double-blind, randomised trial. A favourable overall response occurred in 73.4% of caspofungin recipients and in 61.7% of amphotericin B recipients.In a noncomparative study, salvage therapy with caspofungin (70 mg loading dose followed by 50 mg/day) was effective in patients with invasive aspergillosis who were refractory to or did not tolerate standard antifungal therapy. A favourable response (complete plus partial response) occurred in 37 of 83 patients (45%).Caspofungin was generally well tolerated in clinical trials; it had similar tolerability to intravenous fluconazole and was better tolerated than intravenous amphotericin B. Significantly fewer caspofungin than amphotericin B recipients reported chills, fever, nausea or infusion-related adverse events. In conclusion, caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative trials, caspofungin had similar efficacy to fluconazole and was at least as effective as amphotericin B in oesophageal candidiasis and had similar efficacy to amphotericin B in invasive candidiasis. In addition, caspofungin had similar tolerability to fluconazole and was better tolerated than amphotericin B in these indications. Caspofungin was also effective in patients with invasive aspergillosis who were refractory to or intolerant of standard antifungal agents. Thus, caspofungin provides an alternative to triazoles or amphotericin B in oesophageal candidiasis and an alternative to amphotericin B in invasive candidiasis, as well as being an effective salvage therapy in invasive aspergillosis.     

Caspofungin acetate: an antifungal agent.

The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, and adverse effects of caspofungin acetate are reviewed. Caspofungin acetate is an echinocandin with fungicidal activity against a wide range of pathogens, including Candida spp., Aspergillus spp., and Histoplasma spp. It is active against fluconazole-resistant and fluconazole-susceptible strains of Candida albicans. Caspofungin acetate irreversibly inhibits the enzyme 1,3-beta-D-glucan synthase, preventing the formation of glucan polymers and disrupting the integrity of the fungal cell wall. Caspofungin acetate has an elimination half-life of 9-10 hours and is suitable for once-daily regimens. Data from animal and human studies demonstrate that the drug is 80-96% protein bound. Less than 3% of the dose is eliminated unchanged in the urine, and the proposed route of elimination is hepatic. In a trial of 128 patients with Candida esophagitis, clinical response rates were higher with caspofungin acetate 50 or 70 mg/day (85%) than with amphotericin B 0.5 mg/kg/day (67%). Most enrolled patients had HIV infection, and almost half had CD4+ lymphocyte counts of less than 50 cells/microL in another study, 56 immunocompromised patients with aspergillosis were treated with one 70-mg dose of caspofungin acetate, then 50 mg once a day. All patients had refractory invasive aspergillosis or were intolerant of amphotericin B, liposomal amphotericin B, or azole therapy. In patients who received at least one dose of caspofungin acetate, a favorable response was reported in 41%. In 128 patients who received either caspofungin acetate or amphotericin B, fewer caspofungin acetate recipients (1.4%) had elevated serum creatinine levels and discontinued therapy because of adverse effects (4%) than amphotericin B recipients (15% and 22%, respectively). The manufacturer's recommended dose for infections caused by Candida or Aspergillus spp. has not been determined. Caspofungin acetate appears to be fungicidal, with a wide spectrum of antifungal activity and a good safety profile. The lack of adequate efficacy and safety data in humans makes a recommendation to add this drug to the formulary premature. Pending advanced clinical trials and cost information, caspofungin acetate may be a reasonable addition to the formulary, particularly in hospitals with large immunocompromised patient populations.     

Voriconazole : a review of its use in the management of invasive fungal infections

Voriconazole (VFEND), a synthetic second-generation, broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the cell membrane and halting fungal growth. In the US, intravenous and/or oral voriconazole is recommended in adults for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, disseminated infections caused by Candida spp., oesophageal candidiasis, and in patients with scedosporiosis and fusariosis who are refractory to or intolerant of other antifungal therapy. In Europe, intravenous and/or oral voriconazole is recommended in adults and paediatric patients of at least 2 years of age for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida spp. infections, scedosporiosis and fusariosis.In large randomised trials, voriconazole was an effective and generally well tolerated primary treatment for candidiasis and invasive aspergillosis in adults and adolescents. More limited data also support the use of voriconazole for the treatment of invasive fungal infections in children, in those with rare fungal infections, such as Fusarium spp. or Scedosporium spp., and in those refractory to or intolerant of other standard antifungal therapies. The availability of both parenteral and oral formulations and the almost complete absorption of the drug after oral administration provide for ease of use and potential cost savings, and ensure that therapeutic plasma concentrations are maintained when switching from intravenous to oral therapy. On the other hand, the numerous drug interactions associated with voriconazole may limit its usefulness in some patients. Further clinical experience will help to more fully determine the position of voriconazole in relation to other licensed antifungal agents. In the meantime, voriconazole is a valuable emerging option for the treatment of invasive aspergillosis and rare fungal infections, including Fusarium spp. and Scedosporium spp. infections, and provides an alternative option for the treatment of candidiasis, particularly where the causative organism is inherently resistant to other licensed antifungal agents.     

Caspofungin

Caspofungin is the first in a new class of antifungal agents, the glucan synthesis inhibitors, that interfere with fungal cell wall synthesis. Caspofungin exhibited in vitro and in vivo efficacy against a wide range of fungi and yeasts including Aspergillus and Candida species. A complete or partial response to caspofungin therapy was seen in 40.7% of immunocompromised adults with invasive aspergillosis who did not respond to, or did not tolerate, other antifungal agents in a noncomparative multicentre study. Caspofungin was effective in patients with oropharyngeal or oesophageal candidiasis, according to the preliminary results of 2 randomised double-blind trials. Caspofungin was generally well tolerated in a multicentre noncomparative trial involving patients with invasive aspergillosis. One or more drug-related clinical adverse effects were experienced by 13.8% of caspofungin recipients (the most common were fever, nausea, vomiting and complications associated with the vein into which caspofungin was infused). The tolerability of caspofungin appeared to be better than that of amphotericin B and similar to that of fluconazole in double-blind, randomised trials involving patients with mucosal candidiasis.     

symbol: see text] Seretide and [symbol: see text] Symbicort in asthma management

Maintenance treatment for mild asthma frequently comprises both a regular inhaled corticosteroid and an 'as required' inhaled short-acting beta 2-agonist. Where such treatment fails, additional regular treatment with an inhaled long-acting beta 2-agonist is increasingly recommended. In the UK, combination inhalers containing salmeterol + fluticasone ([symbol: see text] Seretide--Allen & Hanburys) or formoterol + budesonide ([symbol: see text] Symbicort--AstraZeneca) are licensed for use either in "patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled short-acting beta 2-agonists" or in "patients already adequately controlled on both inhaled corticosteroids and long-acting beta 2-agonists". Here we review the efficacy of Seretide and Symbicort and discuss their place in asthma management.     

新型抗真菌药物卡泊芬净

卡泊芬净为美国及欧洲批准的棘球白素类中第一个用于临床的药物,是真菌细胞壁1,3-β-D葡聚糖合成酶抑制剂,用于两性霉素B治疗无效或不能耐受两性霉素B的侵袭性曲霉病成年患者.综述了卡泊芬净(caspofungin)的抗真菌作用机制、药动学及临床评价.     

Caspofungin: new preparation. A last resort in invasive aspergillosis

(1) Invasive aspergillosis is rare. It usually occurs in immunocompromised patients and is fatal despite treatment in 40-90% of cases. The reference treatments are standard amphotericin B, liposomal amphotericin B, and itraconazole. (2) Caspofungin, an antifungal drug, is now approved in the Europe Union for the treatment of invasive aspergillosis, when reference drugs fail or are poorly tolerated. (3) In a non comparative trial in 69 patients, intravenous caspofungin infusion was at least partly effective: 40% of patients survived with few relapses for at least one year following treatment. A historical comparison also favours caspofungin therapy. (4) The safety profile of caspofungin is poorly documented. It includes local reactions at the injection site, systemic reactions linked to the infusion (especially due to histamine release) and hepatic disorders. (5) Caspofungin is known to interact with tacrolimus (lower tacrolimus concentrations), ciclosporin (increased caspofungin bioavailability) and rifampicin (reduced caspofungin bioavailability). (6) In practice, caspofungin is an acceptable option for the treatment of invasive aspergillosis when standard amphotericin B, liposomal amphotericin B, and itraconazole are ineffective or poorly tolerated. Its clinical assessment is limited and must be continued.     

Review of the safety,tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole

Managing invasive fungal infections often presents a challenge for clinicians in the treatment of immunocompromised patients. Two very different systemic antifungal agents, voriconazole and caspofungin, have recently been introduced into the market place. Voriconazole is a new triazole antifungal, while caspofungin is the first echinocandin antifungal. Voriconazole acts by inhibiting the synthesis of ergosterol in the fungal cell membrane. Caspofungin inhibits beta-1,3-D-glucan synthesis in the cell wall, a target present in fungal cells, but absent from mammalian cells. Both agents are broad-spectrum, with efficacy against invasive Aspergillus and Candida infections. The safety and tolerability profile of caspofungin presented with a low incidence of adverse events in clinical trials. Pending further data, coadministration of cyclosporine has been recommended only if the benefit outweighs the risk for patients. Voriconazole has three important side-effects that the clinician must consider: liver abnormalities, skin abnormalities and visual disturbances. Liver abnormalities in particular should be monitored very carefully. The drug interaction profile of voriconazole also warrants a careful evaluation of the concomitant medication, mainly due to cytochrome P450 metabolism. This article reviews the available data concerning the safety and tolerability profiles of each drug, as well as drug interactions and contraindications.     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.     

symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?

[symbol: see text] Nateglinide (Starlix-Novartis) and [symbol: see text] repaglinide (NovoNorm-Novo Nordisk) are two of a new class of orally active antidiabetic drugs, the meglitinides. They have a rapid-onset and short-lasting stimulating effect on insulin secretion. Both are licensed for combination therapy with metformin in patients with type 2 diabetes mellitus who are inadequately controlled by maximally tolerated doses of metformin alone. In addition, repaglinide is licensed for use as monotherapy in patients with type 2 diabetes whose hyperglycaemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Here we discuss whether repaglinide and nateglinide offer worthwhile advantages in the management of patients with type 2 diabetes.     

Echinocandins: role in antifungal therapy, 2005

Novel therapies to treat invasive fungal infections have revolutionised the care of patients with candidiasis, aspergillosis and other less common fungal infections. Physicians in the twenty first century have access to safer versions of conventional drugs (i.e., lipid amphotericin B products), extended-spectrum versions of established drugs (i.e., voriconazole), as well as a new class of antifungal agents; the echinocandins. The increased number of options in the antifungal armamentarium is well timed, as the incidence of both invasive candidiasis and invasive aspergillosis, and the financial burden associated with these infections, have increased significantly in the past several decades. The increasing incidence of fungal infections has risen in parallel with the increase in critically ill and immunocompromised patients. Candida is the fourth most common bloodstream isolate, approximately 50% of which are non-albicans species. Estimates suggest there to be 9.8 episodes of invasive candidiasis per 1000 admissions to surgical intensive care units, with attributable mortality at 30% and cost per episode of US44,000 dollars. The burden of candidiasis is even higher in the paediatric population, with Candida being the second most common bloodstream infection. The increase in non-albicans candidiasis mandates the introduction of new antifungal agents capable of treating these often azole-resistant isolates. In addition, there has been a rise in the incidence of invasive aspergillosis, the most common invasive mould infection following haematopoietic stem cell transplantation, with an estimated incidence of 10 - 20%. The mortality associated with invasive aspergillosis has increased by 357% since 1980. Unfortunately, the overall survival rate among patients treated with amphotericin B, and even voriconazole, remains suboptimal, as evidenced by the failure of treatment in 47% of patients in the landmark voriconazole versus amphotericin B trial. Given the increasing incidence and suboptimal outcomes of these serious fungal infections, novel therapies represent an opportunity for significant advancement in clinical care. The current challenge is to discover the optimal place for the echinocandins in the treatment of invasive fungal infections.     

The pharmacology and clinical use of caspofungin

Caspofungin was the first echinocandin to be licensed for the treatment of invasive fungal infections. Caspofungin has in vitro and in vivo activity against Candida spp. and Aspergillus spp., which constitute the majority of medically important opportunistic fungal pathogens. Caspofungin inhibits the synthesis of the 1,3-beta-glucan, with resultant osmotic instability and lysis. The pharmacology of caspofungin is relatively complex. Trafficking of drug into tissues is an important determinant of the shape of the concentration-time relationship. Caspofungin has demonstrated efficacy in experimental models of invasive candidiasis and aspergillosis, which reflect its activity in the treatment of oropharyngeal, esophageal and disseminated candidiasis, as well as salvage therapy for patients with invasive aspergillosis.     

symbol: see text] Tiagabine: add-on treatment for partial seizures

Up to 30% of patients with epilepsy have seizures resistant to available treatments. We consider here the place of [symbol: see text] tiagabine (Gabitril-Sanofi-Synthelabo), which was recently introduced as an "add-on therapy for partial seizures with or without secondary generalisation where control is not achieved by optimal doses of at least one other anti-epileptic".     

新型抗真菌药物caspofungin

caspofungin是新型葡聚糖合成酶抑制剂类抗真菌药物中第 1个上市的药物 ,它能有效抑制 β ( 1,3) D 葡聚糖的合成 ,从而干扰真菌细胞壁的合成。caspofungin在体内、外具有广泛的抗真菌活性 ,包括曲菌和念珠菌。多中心试验表明 ,caspofungin治疗难治性或不能耐受其他治疗的侵袭性曲菌感染病人的临床有效率为 4 0 .7%。 2个随机双盲试验表明 ,caspofungin能有效治疗咽或食道念珠菌感染。侵袭性曲菌病人对caspofungin的耐受性较好。本文综述了caspofungin的药效学、药动学特性、临床疗效和不良反应等。     

The role of caspofungin and the echinocandins in the antifungal armamentarium

The echinocandins are a recently-developed class of antifungal agents that interfere with fungal cell wall synthesis through the inhibition of glucan synthesis. Although several intravenous preparations are in various stages of development, caspofungin is the only currently approved agent and no oral echinocandin derivatives are presently available. Caspofungin is approved for the treatment of invasive aspergillosis in patients who are refractory to, or intolerant of, other antifungal therapies. This agent has activity against most Candida species, and in a prospective randomized trial, was as effective as, and better tolerated than amphotericin B in the treatment of candidal esophagitis. Activity against the cyst form of Pneumocystis carinii has also been demonstrated. Caspofungin is administered in a daily intravenous dose, and is well tolerated. Concomitant use of this agent with cyclosporine is presently not recommended. Other echinocandin derivatives presently in phase II/III clinical development include micafungin and anidulafungin.