Echinocandin antifungal drugs in fungal infections: a comparison

This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed echinocandins: caspofungin, micafungin and anidulafungin. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections. The echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including azole-resistant pathogens. For all agents, strains with drug minimum inhibitory concentrations (MICs) of ≤ 2?μg/mL are considered susceptible; the MIC at which 90% of isolates tested were inhibited (MIC??) values are typically <2?μg/mL but 100-fold higher MIC?? values are seen with Candida parapsilosis (1-2?μg/mL) and Candida guilliermondii (1-4?μg/mL). Activity is comparable between the three agents, although limited data indicate that anidulafungin may have low MICs against C. parapsilosis and Candida glabrata strains that demonstrate elevated MICs to caspofungin and micafungin. All three drugs have good fungistatic activity against Aspergillus spp., although minimal effective concentrations of micafungin and anidulfungin are 2- to 10-fold lower than those for caspofungin. Synergistic/additive in vitro effects of echinocandins when combined with a polyene or azole have been observed. Clinical resistance to the echinocandins is rare despite case reports of caspofungin resistance in several Candida spp. Resistance has been attributed to mutations in the FKS1 gene within two hot spot regions, leading to amino acid substitutions, mostly at position 645 (serine), yet not all FKS1 mutants have caspofungin MICs of >2?μg/mL. Of the three echinocandins, the in vitro 'paradoxical effect' (increased growth at supra-MIC drug concentrations) is observed least often with anidulafungin. All echinocandins have low oral bioavailability, and distribute well into tissues, but poorly into the CNS and eye. Anidulafungin is unique in that it undergoes elimination by chemical degradation in bile rather than via hepatic metabolism, has a lower maximum concentration and smaller steady state under the concentration-time curve but longer half-life than caspofungin or micafungin. In children, dosing should be based on body surface area. Daily doses of caspofungin (but not micafungin and anidulafungin) should be decreased (from 50 to 35?mg) in moderate liver insufficiency. All echinocandins display concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus) activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5 hours against Aspergillus. The echinocandins are well tolerated with few serious drug-drug interactions since they are not appreciable substrates, inhibitors or inducers of the cytochrome P450 or P-glycoprotein systems. In parallel with the greater clinical experience with caspofungin, this agent has a slightly higher potential for adverse effects/drug-drug interactions, with the least potential observed for anidulafungin. Caspofungin (but not micafungin or anidulafungin) dosing should be increased if coadministered with rifampicin and there are modest interactions of caspofungin with calcineurin inhibitors. All three agents are approved for the treatment of oesophageal candidiasis, candidaemia and other select forms of invasive candidiasis. Only micafungin is licensed for antifungal prophylaxis in stem cell transplantation, whereas caspofungin is approved for empirical therapy of febrile neutropenia. Caspofungin has been evaluated in the salvage and primary therapy of invasive aspergillosis. Combination regimens incorporating an echinocandin showing promise in the treatment of aspergillosis. However, echinocandins remain expensive to use.     

Micafungin: a review of its use in adults for the treatment of invasive and oesophageal candidiasis, and as prophylaxis against Candida infections

Intravenous micafungin (Mycamine; Fungard), an echinocandin, inhibits the synthesis of 1,3-beta-D-glucan, an essential cell wall component in many fungi. It is approved in adults (focus of this review) and in neonates and paediatric patients (Pediatric Drugs [in press]) in the EU and elsewhere for the treatment of invasive candidiasis and oesophageal candidiasis, and as prophylactic treatment to prevent Candida infections in haematopoietic stem cell transplant (HSCT) recipients.Intravenous micafungin shows very good activity against clinically relevant isolates of Candida spp. Furthermore, the pharmacokinetic profile of micafungin permits once-daily treatment and means that it is associated with relatively few drug-drug interactions. However, like all of the echinocandins and all formulations of amphotericin B, micafungin must be given intravenously. In large, well designed clinical trials in adult patients (>or=16 years of age) with invasive candidiasis, intravenous micafungin was shown to be noninferior to intravenous caspofungin or liposomal amphotericin B. In similarly designed trials in adult patients with oesophageal candidiasis, intravenous micafungin was shown to be noninferior to fluconazole or caspofungin treatment. As prophylactic treatment in adult and paediatric patients who had undergone HSCT, micafungin was superior to fluconazole therapy in a large, well designed trial. Micafungin was generally well tolerated by participants in these clinical trials. Furthermore, it was as well tolerated as caspofungin and fluconazole, and better tolerated than liposomal amphotericin B. The position of micafungin relative to newer antifungal therapies, such as anidulafungin, voriconazole and posaconazole, remains to be fully determined. Thus, micafungin is an emerging option for the treatment of adult patients with invasive or oesophageal candidiasis, and as prophylaxis against Candida infections in HSCT recipients.     

The echinocandins

The changing pattern in fungal infections has driven the need to expand the targets of antifungal activity. The echinocandins are the newest addition to the arsenal against fungal infections. Three echinocandins have been approved by the United States Food and Drug Administration: caspofungin, micafungin, and anidulafungin. These agents have a broad spectrum of activity and are similar to each other with respect to in vitro activity against Candida sp, with micafungin and anidulafungin having similar minimum inhibitory concentrations (MICs) that are generally lower than the MIC of capsofungin. The MICs of the echinocandins are highest against Candida parapsilosis; however, whether this will affect clinical outcomes is unknown. Several case reports have identified clinical failure due to elevated MICs with caspofungin or micafungin against Candida albicans, Candida krusei, and C. parapsilosis. Resistance to the echinocandin class was present in some but not all of the isolates. Empiric therapy with one of the echinocandins for candidemia or invasive candidiasis in patients with neutropenia and those without neutropenia appears to be appropriate when one factors in mortality rate, the increasing frequency of non-albicans Candida infections, and the broad spectrum, safety, and fungicidal effect of the echinocandins. After speciation of the organism, continued therapy with an echinocandin can and should be reevaluated. The echinocandins demonstrate similar in vitro and in vivo activity against Aspergillus sp, but only caspofungin is approved for treatment in patients who are intolerant of or refractory to other therapies. Voriconazole and amphotericin B have demonstrated synergy with the echinocandins. The clinical response to combination therapy has been variable; however, the mortality rate appears to be lower with combination therapy than monotherapy. Large controlled trials are needed to determine the role of combination therapy for invasive aspergillosis. Micafungin and anidulafungin generally have a lower frequency of adverse reactions compared with caspofungin. Phlebitis (3.5-25% of patients) and elevated liver enzyme levels (1-15%) occur more often with caspofungin compared with micafungin and anidulafungin (< 8%). Overall, the three echinocandins are relatively safe and effective agents for the treatment of Candida infections.     

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.     

Developments in the treatment of candidiasis: more choices and new challenges

The incidence of oesophageal candidiasis, candidaemia and disseminated candidiasis has increased dramatically. In addition to the amphotericin B formulations and fluconazole, the echinocandins anidulafungin, caspofungin and micafungin and the newer triazoles posaconazole and voriconazole are in the last stages of development and are becoming available for the management of candidiasis. This review presents these new agents and addresses their role in the treatment of candidiasis. All new antifungal agents exhibit potent activity against Candida spp. and echinocandins are fungicidal against most Candida spp. but appear to be less potent against certain species, such as Candida parapsilosis and C. guilliermondii. Systemic antifungal therapy can now be individualised based on the severity of the infection, comorbid conditions and the Candida spp. causing the infection. Studies are needed to investigate the possible development of resistance and the efficacy of these antifungal agents against the more resistant Candida spp.     

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.     

Emerging echinocandins for treatment of invasive fungal infections

The echinocandins are a new class of antifungals, developed in response to the need for safe and effective antifungals for the treatment of invasive fungal infections. These agents work by inhibiting 1,3-beta-d-glucan synthase, an enzyme essential for production of cell walls in select fungi. Echinocandins appear to demonstrate favourable activity in vitro against a variety of yeasts (including both Candida albicans and non-albicans Candida) as well as select moulds (including Aspergillus spp.) In general, all echninocandins demonstrate a favourable safety profile and require once-daily parenteral administration. Caspofungin is the first of these agents to be available in the US, and is approved for empirical antifungal therapy in febrile neutropenic patients, candidaemia and select forms of invasive candidiasis, and for management of invasive aspergillosis in patients refractory to or intolerant of other therapies. Micafungin was recently approved by the FDA for treatment of oesophageal candidiasis, and for the prophylaxis of fungal infections in haematopoietic stem cell transplant recipients. Emerging data indicate micafungin may have an important role in the treatment of invasive forms of candidiasis. Anidulafungin is an echinocandin approved in the US for treatment of candidaemia and oesophageal candidiasis. Aminocandin (HMR-3702, IP-960) is an investigational agent, with published experience limited to in vitro studies and animal models of infection.     

A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-β-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.     

A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-beta-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.     

Micafungin: a new echinocandin antifungal

The echinocandins represent the newest class of antifungals to combat infections caused by Candida sp. Micafungin is an echinocandin recently approved by the United States Food and Drug Administration. It is indicated in adults for esophageal candidiasis and prophylaxis against candidal infections in hematopoietic stem cell transplant recipients. Micafungin exhibits in vitro fungicidal activity against Candida sp, including fluconazole-resistant isolates. Its in vivo efficacy is comparable to that of fluconazole in the treatment of esophageal candidiasis and superior to that of fluconazole for prophylaxis of invasive candidal infections. Because it is not significantly metabolized by the cytochrome P450 3A system, micafungin is associated with few drug interactions. Micafungin does not require adjustment in patients with renal and/or hepatic impairment, and it has been shown to be well tolerated in both adult and pediatric patients. Its efficacy against Candida sp, coupled with its overall safety and drug interaction profiles, makes it an attractive option in the treatment against esophageal candidiasis and prophylaxis against invasive candidal infections.     

Recent advances in antifungal agents

New antifungals are needed in the medicine because of more aggressive and invasive diagnostic and therapeutic methods used, rapid emergence of resistant and new opportunistic fungi, increasing number of patients suffering from immunosuppressive situations e.g., AIDS, transplantation, cancer, etc. Several classes of new antifungal agents are discussed here including some new members of known families. Voriconazole, posaconazole and ravuconazole, are novel triazoles that inhibit the ergosterol synthesis. These drugs overcome problems associated with the ineffectivity of fluconazole against some Aspergillus spp. or the variable bioavailability of itraconazole. Echinocandins (caspofungin, anidulafungin and micafungin) represent a new family of antifungal agents that inhibit 1,3-beta-glucan synthase. Nikkomycins targeting the chitin synthase, show activity against Histoplasma capsulatum and Blastomyces dermatitidis. Sordarin derivatives that block the fungal protein synthesis can be considered as a promising new class of antifungal agents for the treatment of Candida and Pneumocystis infections.     

Anidulafungin: an echinocandin antifungal

Anidulafungin (LY-303366, V-echinocandin trade mark, Vicuron Pharmaceuticals, Inc.) is a new echinocandin antifungal agent with broad spectrum activity against Candida and Aspergillus spp. Anidulafungin exhibits low toxicity, concentration-dependent fungicidal activity for Candida, and a prolonged post antifungal effect (> 12h). In vitro activity demonstrates excellent potency and spectrum versus azole-susceptible and -resistant Candida spp. and a low minimum effective concentration for Aspergillus spp. In vivo anidulafungin is fungicidal against Candida in neutropenic animal models of disseminated candidiasis. Against Candida anidulafungin exhibits concentration-dependent killing and clearance of residual fungal burden in target organs (liver, lung, spleen, kidney) and plasma/tissue concentrations exceed the minimum inhibitory and minimum fungicidal concentrations of the infecting organism throughout the dosing interval. Although the activity of anidulafungin in animal models of pulmonary or disseminated aspergillosis shows increased survival and improvement in the pulmonary infarct score, the effect on residual fungal burden and Aspergillus antigenemia determination does not indicate in vivo fungicidal activity. It seems that the major effect of anidulafungin and other echinocandins in vivo against Aspergillus spp. is the decrease in the angioinvasive potential of the organisms. Clinically, anidulafungin has been shown to be safe and effective in the treatment of oesophageal candidiasis and candidemia. Further clinical application of this new antifungal agent is warranted.     

Anidulafungin: an echinocandin antifungal

Anidulafungin (LY-303366, V-echinocandin?, Vicuron Pharmaceuticals, Inc.) is a new echinocandin antifungal agent with broad spectrum activity against Candida and Aspergillus spp. Anidulafungin exhibits low toxicity, concentration-dependent fungicidal activity for Candida, and a prolonged post antifungal effect (> 12h). In vitro activity demonstrates excellent potency and spectrum versus azole-susceptible and -resistant Candida spp. and a low minimum effective concentration for Aspergillus spp. In vivo anidulafungin is fungicidal against Candida in neutropenic animal models of disseminated candidiasis. Against Candida anidulafungin exhibits concentration-dependent killing and clearance of residual fungal burden in target organs (liver, lung, spleen, kidney) and plasma/tissue concentrations exceed the minimum inhibitory and minimum fungicidal concentrations of the infecting organism throughout the dosing interval. Although the activity of anidulafungin in animal models of pulmonary or disseminated aspergillosis shows increased survival and improvement in the pulmonary infarct score, the effect on residual fungal burden and Aspergillus antigenemia determination does not indicate in vivo fungicidal activity. It seems that the major effect of anidulafungin and other echinocandins in vivo against Aspergillus spp. is the decrease in the angioinvasive potential of the organisms. Clinically, anidulafungin has been shown to be safe and effective in the treatment of oesophageal candidiasis and candidemia. Further clinical application of this new antifungal agent is warranted.     

symbol: see text]Caspofungin and [symbol: see text]voriconazole for fungal infections

Systemic fungal infections are difficult to treat and often fatal. Established treatment options include conventional amphotericin B or one of its lipid-based or liposomal formulations, or a triazole antifungal such as fluconazole or itraconazole. [symbol: see text]Caspofungin (Cancidas--Merck Sharp & Dohme) and [symbol: see text]voriconazole (Vfend--Pfizer) are two new antifungals for severe infections caused by Candida spp. (invasive candidiasis) and Aspergillus spp. (invasive aspergillosis). Caspofungin is the first licensed echinocandin antifungal, while voriconazole is a triazole. Promotional claims for caspofungin include that it "provides an effective, yet less toxic, alternative to amphotericin B" while voriconazole is claimed to offer "significantly improved survival in invasive aspergillosis compared with amphotericin B". Here we consider the place of caspofungin and voriconazole in managing patients with severe 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.     

Echinocandins in the management of invasive fungal infections, part 1.

PURPOSE: The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effiects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed. SUMMARY: Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-dglucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration- dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming. CONCLUSION: Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.     

Caspofungin: the first in a new class of antifungal agents.

Caspofungin is the first approved agent from a new class of antifungals, the echinocandins. By targeting the fungal cell wall (as opposed to the fungal cell membrane), the echinocandins exhibit a unique mechanism of action relative to the other currently approved antifungal agents. Preclinical (in vitro and in vivo) studies have demonstrated activity for caspofungin against the most commonly encountered fungi in the hospital setting, namely Candida and Aspergillus species. Caspofungin is administered as a once-a-day, intravenous formulation. Notably, caspofungin is neither an inhibitor, inducer, nor metabolite of the cytochrome p450 system. To date, few drug-drug interactions have been seen for this echinocandin. A number of Phase II and III clinical studies in documented invasive candidiasis, esophageal candidiasis, and invasive aspergillosis have been completed and have demonstrated efficacy for caspofungin against all three diseases. In all studies, caspofungin manifested an excellent safety profile with few serious, drug-related adverse events or discontinuations due to drug-related adverse events. Isolated symptoms compatible with histamine release have been infrequently reported. In clinical studies, drug-related nephrotoxicity with caspofungin has been rare, and the incidence of liver transaminase elevations has been similar to the incidence seen with comparator agents. Results from a Phase III study as empirical therapy in patients with febrile neutropenia are anticipated in late 2003. Overall, caspofungin represents an important addition to the current antifungal armamentarium.     

A review of the new antifungals: posaconazole, micafungin, and anidulafungin

This column reviews 3 new systemic antifungal agents (posaconazole, micafungin, and anidulafungin) from the standpoint of dermatology. Posaconazole, approved to treat invasive Aspergillus and Candida infections, is available in an oral suspension and resembles fluconazole, but seems to have a broader spectrum of activity. Posaconazole is effective against yeasts and molds and could be effective in treating rare fungal infections involving Zygomycetes, Mucor necrotizing fasciitis, rhinocerebral mucormycosis, some Fusarium species, Penicillium, Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, and sporotrichosis, chromoblastomycosis, mycetoma, and phaeohyphomycosis, including Scedosporium apiospermum and Exophiala, Alternaria, and Bipolaris species. Posaconazole may abate onychomycosis and dermatophytes, but clinical trial data is lacking. Micafungin and anidulafungin are echinocandins like caspofungin and are useful salvage therapy for invasive aspergillosis and candidiasis. The exciting new agents have extended the armamentarium against antifungal pathogens, but have yet to find their place in the dermatologic practice.     

Echinocandins in the management of invasive fungal infections, Part 2.

PURPOSE: The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed. SUMMARY: Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-D-glucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration-dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming. CONCLUSION: Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.     

Análisis de costes de tres candinas en el tratamiento de la candidiasis invasora en pacientes adultos no neutropénicos en España

ObjectiveTo estimate the cost of 3 candins (anidulafungin, caspofungin and micafungin) in the treatment of adult non-neutropaenic patients with invasive candidiasis (IC) in a Spanish hospital pharmacy setting.MethodsThe overall cost impact was evaluated by varying the percentage dosage required of each candin in different possible scenarios. The prices (in euros) for each presentation were obtained from the Drug Catalogue (in August 2010). Only drug purchase costs were considered. The results are expressed as total cost for each of the 3 candins.ResultsThe cost per episode (14 days) of anidulafungin was constant at €5400 per patient. The cost of caspofungin varied from €4281 to €7991, depending on patient weight and liver dysfunction. The cost of micafungin varied from €6000 (100 mg/day) to €9000 (when increasing the dose due to inadequate response). Based on a hypothetic cohort of 100 patients with IC, the total cost of anidulafungin treatment would be €540 000, for caspofungin it would be €631 459, and for micafungin it would be €632 998, depending on any dose adjustment required.ConclusionPatients treated with anidulafungin did not require dose adjustment, unlike those treated with caspofungin or micafungin. The use of anidulafungin is a cost-saving treatment for adult non-neutropaenic patients with IC, which would result in better control of the Spanish pharmacy budget.