Antifungal prophylaxis in adult hematopoietic stem cell transplant recipients

Invasive fungal infections (IFIs) are a frequent, costly and potentially life-threatening complication in hematopoietic stem cell transplant (HSCT) recipients. Most prevalent among the causative pathogens are Candida spp. and Aspergillus spp. Risk factors that further increase the risk of IFIs in this patient population include allogeneic transplant and acute graft versus host disease. Among strategies to improve outcomes is the administration of antifungal prophylaxis. However, optimal administration requires the identification of patients who are at the highest risk of developing a fungal infection, thus restricting concerns of drug cost, toxicity and resistance to those most likely to benefit. Currently, there are several antifungal agents recommended by the National Comprehensive Cancer Network for the prophylaxis of IFIs. These include fluconazole, itraconazole, voriconazole, posaconazole and micafungin. Fluconazole was widely considered the standard agent for prophylaxis in patients at lower risk of mold infections. New data support the efficacy of the newer triazole posaconazole and the echinocandin micafungin in this patient population..     

Caspofungin as primary antifungal prophylaxis in stem cell transplant recipients

STUDY OBJECTIVES: To assess the effectiveness and tolerability of caspofungin as primary prophylaxis against invasive fungal infections in stem cell transplant recipients who are poor candidates for triazole or lipid amphotericin B prophylaxis due to renal or hepatic dysfunction, and to determine whether any patient characteristics are independently associated with an increased risk of breakthrough invasive fungal infection during caspofungin prophylaxis. DESIGN: Retrospective medical record review. SETTING: Tertiary care comprehensive cancer center. PATIENTS: One hundred twenty-three adult stem cell transplant recipients who received caspofungin 35-50 mg/day for up to 100 days after transplantation as primary antifungal prophylaxis between January 1, 2002, and June 30, 2005. MEASUREMENTS AND MAIN RESULTS: Data were collected on host and transplant characteristics such as transplant type, neutropenia, graft-versus-host disease (GVHD), and corticosteroid use, as well as evidence of breakthrough invasive fungal infections. Of the 123 patients, 117 (95.1%) were allogeneic recipients, and the median time to engraftment was 12 days (range 6-26 days). Fifty (40.7%) of the patients developed GVHD of grade 2 or greater and received corticosteroids for more than 21 days. Median duration of caspofungin prophylaxis was 73 days (range 10-100 days). Nine patients (7.3%) developed breakthrough invasive fungal infections (two cases of mixed Aspergillus species and one each of Aspergillus terreus, Rhizopus, Exserohilum, an unspecified mold, Cryptococcus, Candida glabrata, and Candida tropicalis). Median time to invasive fungal infection development was 65 days (range 12-88 days). Only one case occurred during the neutropenic period before engraftment. Multivariate analysis showed that Pseudomonas coinfection (p=0.04) and infliximab therapy (p=0.02) were associated with breakthrough invasive fungal infections in patients receiving caspofungin. By day 100, there were five (4.1%) deaths, two of which were directly attributable to invasive fungal infections. No caspofungin-related adverse events were reported. CONCLUSION: Caspofungin seems to be an effective and well-tolerated option for primary antifungal prophylaxis in the highly immunosuppressed stem cell transplant patient population.     

Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease

STUDY OBJECTIVE: To analyze the pharmacokinetics of posaconazole administered as prophylaxis for invasive fungal infections in recipients of hematopoietic stem cell transplants (HSCTs) who have graft-versus-host disease (GVHD). DESIGN: Pharmacokinetic analysis in a subset of posaconazole-treated patients from a large, multicenter, phase III, randomized, double-blind, double-dummy, parallel-group trial that compared posaconazole with fluconazole. SETTING: Ninety international medical centers. PATIENTS: The subset of patients comprised 246 HSCT recipients for whom pharmacokinetic data were available. INTERVENTION: All patients received posaconazole 200 mg oral suspension 3 times/day for a maximum of 16 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected after dosing on day 2; at weeks 2, 4, 8, and 12; and on the last day of oral treatment. After patients had received posaconazole for at least 7 days (i.e., after achieving steady state), both maximum observed posaconazole concentration (C(max)) and average posaconazole concentration (C(av)) were determined. Five patients developed invasive fungal infections while receiving treatment. Median C(av) and C(max) were 611 and 635 ng/ml, respectively, in these five patients and were 922 and 1360 ng/ml, respectively, in the 241 patients without invasive fungal infection. In patients without invasive fungal infection, posaconazole concentrations were not clinically affected by race, body weight, or age. Median plasma posaconazole concentrations were higher in patients with chronic GVHD than in those with acute GVHD. In 18 patients without invasive fungal infection who experienced diarrhea on the day of sampling, posaconazole concentrations were lower than the concentrations in patients without diarrhea. No relationship was observed between alanine aminotransferase, aspartate aminotransferase, or bilirubin levels and posaconazole concentrations. CONCLUSION: Posaconazole 200 mg 3 times/day resulted in median plasma drug concentrations sufficiently high to prevent invasive fungal infections in HSCT recipients with GVHD, without compromising patient safety. Plasma posaconazole concentrations are generally unaffected by demographic variables, including race, sex, body weight, and age.     

Posaconazole

Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit (primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase II study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for >or=1 year.     

In vitro antifungal activity of posaconazole against various pathogenic fungi

The antifungal activity of posaconazole (SCH56592), a new triazole antifungal, against stock cultures and fresh clinical isolates of a wide range of pathogenic fungi was compared with that of itraconazole, fluconazole and amphotericin B. Posaconazole inhibited growth of all the fungal species tested except Fusarium spp. at 1 mg/l or lower concentrations, showing a broad-spectrum antifungal activity. The activities of posaconazole for all the fungal species far surpassed those of fluconazole and were even superior to those of itraconazole for Aspergillus spp. as well as for many other fungal species.     

Novel triazole antifungal agents

The risk of opportunistic infections is greatly increased in patients who are immunocompromised due to AIDS, cancer chemotherapy and organ or bone marrow transplantation. Candida albicans is often associated with serious systemic fungal infections, however other Candida species such as Candida krusei, Candida tropicalis and Candida glabrata, as well as Cryptococcus neoformans and filamentous fungi such as Aspergillus, have also emerged as clinically significant fungal pathogens. Two triazole antifungal agents, fluconazole and itraconazole, were introduced over a decade ago and since then have been used extensively for the prophylaxis and treatment of a variety of fungal infections. Although both drugs are effective and have their place in therapy, limitations regarding the utility of these agents do exist. For example, fluconazole is not effective for the prophylaxis or treatment of Aspergillus species and has limited activity against C. krusei and C. glabrata. The use of itraconazole has been limited secondary to concerns regarding unpredictable bioavailability. The rising incidence of fungal infections and the reported increase of non-albicans candidal infections noted over the past two decades highlight the need for new antifungal agents with improved spectra of activity. Several new triazole agents are in various phases of preclinical and clinical trials and may be available for human use in the near future. Three such agents voriconazole, posaconazole and ravuconazole are reviewed and compared with existing agents.     

Novel triazole antifungal agents

The risk of opportunistic infections is greatly increased in patients who are immunocompromised due to AIDS, cancer chemotherapy and organ or bone marrow transplantation. Candida albicans is often associated with serious systemic fungal infections, however other Candida species such as Candida krusei, Candida tropicalis and Candida glabrata, as well as Cryptococcus neoformans and filamentous fungi such as Aspergillus, have also emerged as clinically significant fungal pathogens. Two triazole antifungal agents, fluconazole and itraconazole, were introduced over a decade ago and since then have been used extensively for the prophylaxis and treatment of a variety of fungal infections. Although both drugs are effective and have their place in therapy, limitations regarding the utility of these agents do exist. For example, fluconazole is not effective for the prophylaxis or treatment of Aspergillus species and has limited activity against C. krusei and C. glabrata. The use of itraconazole has been limited secondary to concerns regarding unpredictable bioavailability. The rising incidence of fungal infections and the reported increase of non-albicans candidal infections noted over the past two decades highlight the need for new antifungal agents with improved spectra of activity. Several new triazole agents are in various phases of preclinical and clinical trials and may be available for human use in the near future. Three such agents voriconazole, posaconazole and ravuconazole are reviewed and compared with existing agents.     

Posaconazole: a new broad-spectrum antifungal agent

The rising incidence of invasive fungal infections and the emergence of broader fungal resistance have led to the need for novel antifungal agents. Posaconazole is a new member of the triazole class of antifungals. It is available as an oral suspension and has a favorable toxicity profile, has demonstrated clinical efficacy in the treatment of oropharyngeal candidiasis and has shown promise as salvage therapy for invasive aspergillosis, zygomycosis, cryptococcal meningitis and a variety of other fungal infections. In addition, data from randomized controlled studies support its efficacy for use in prophylaxis of invasive fungal infections in patients who are severely immunocompromised. The wide spectrum activity of posaconazole in in vitro studies, animal models and preliminary clinical studies suggest that posaconazole represents an important addition to the antifungal armamentarium.     

新型广谱三唑类抗真菌药泊沙康唑

泊沙康唑为一新型三唑类抗真菌药，用于治疗和预防侵袭性真菌感染。体内外试验表明，其具有广谱抗菌活性，对念珠菌属、新隐球菌属、曲霉菌属、接合菌属和地方真菌有效，并有良好的耐受性，不良反应轻微。现对其作用机制、药动学、临床评价及不良反应做一综述。     

Posaconazole

Invasive fungal infections are occurring with increasing frequency secondary to medical advances in the areas of transplantation, cancer management and autoimmune diseases. Unfortunately, the currently available antifungal armamentarium does not meet the increasing needs of managing infection in these complex patient populations. Posaconazole, a new triazole antifungal agent, is being investigated for its role in treating serious infections due to yeasts and molds. This new drug offers an expanded spectrum of activity over other members of its class. In addition to potent activity against fluconazole-resistant Candida and refractory cases of aspergillosis, posaconazole demonstrates activity against Zygomycetes. Posaconazole is a well-tolerated agent that offers a diminished toxicity profile compared with other currently marketed systemic antifungal agents. Clinical success rates thus far have been promising, although the exact role of this agent in treating and preventing invasive fungal infections is yet to be determined.     

Posaconazole: a new broad-spectrum antifungal agent

The rising incidence of invasive fungal infections and the emergence of broader fungal resistance have led to the need for novel antifungal agents. Posaconazole is a new member of the triazole class of antifungals. It is available as an oral suspension and has a favorable toxicity profile, has demonstrated clinical efficacy in the treatment of oropharyngeal candidiasis and has shown promise as salvage therapy for invasive aspergillosis, zygomycosis, cryptococcal meningitis and a variety of other fungal infections. In addition, data from randomized controlled studies support its efficacy for use in prophylaxis of invasive fungal infections in patients who are severely immunocompromised. The wide spectrum activity of posaconazole in in vitro studies, animal models and preliminary clinical studies suggest that posaconazole represents an important addition to the antifungal armamentarium.     

Patients at high risk of invasive fungal infections: when and how to treat

When and how to treat invasive fungal infections (IFIs) is discussed in this review, with a focus on the two most prevalent non-endemic IFIs, namely invasive aspergillosis and invasive candidiasis. Early treatment initiation in patients with IFIs has a profound impact on mortality rates, but reliable diagnostic measures are lacking. This situation has led to the parallel use of different treatment strategies, e.g. prophylaxis, empirical and pre-emptive treatment, as well as targeted treatment in response to a definite diagnosis of IFI. Identifying high-risk patients is the first step in reducing IFI-related mortality. Patients at risk of invasive aspergillosis comprise (i) those with acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) during remission induction chemotherapy; (ii) patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT); (iii) recipients of solid organ transplants; and (iv) those with other conditions of severe and prolonged immunosuppression. Patients at high risk of invasive candidiasis are less well defined. Risk factors are diverse and include haematological malignancy, neutropenia, age <1 month or >65 years, and recent abdominal surgery. The individual risk further depends on the presence of a variety of other risk factors, including central venous catheters, use of broad spectrum antibacterials, prolonged intensive care unit (ICU) stay, total parenteral nutrition, mucosal Candida spp. colonization and renal failure.Extensive research has been conducted to facilitate the best possible treatment strategies for these severe infections. Optimal timing and choice of antifungal agents largely remain a matter of controversy. After having reviewed the major clinical trials, we conclude that comparisons between different treatment strategies cannot be made, neither at present nor in the near future. The complexity of the clinical problem leads to an eclectic treatment approach to reduce morbidity and mortality from IFIs without compromising tolerability. We recommend prophylaxis with posaconazole for allogeneic HSCT recipients, patients receiving induction chemotherapy for AML or MDS, and those undergoing immunosuppressive therapy for graft-versus-host disease after allogeneic HSCT. For the empirical treatment of persistently febrile neutropenia, caspofungin is our first- and liposomal amphotericin B deoxycholate (LAmB) our second-line choice. Once a diagnosis of invasive aspergillosis has been established, voriconazole should be the preferred treatment option, with LAmB being an alternative. Fluconazole prophylaxis for invasive candidiasis should remain restricted to high-risk ICU patients. Once a diagnosis has been established, the drug of choice for adequate treatment depends largely on neutrophil count and haemodynamic stability. In non-neutropenic patients, an echinocandin should be considered the first-line treatment option, while patients with susceptible Candida spp. may be switched to fluconazole. In neutropenic patients, caspofungin or micafungin might be preferred to anidulafungin as first-line treatment. LAmB is a second-line treatment option in both settings.Early diagnosis of IFIs is imperative to facilitate treatment success. In all patients at risk for IFIs, blood cultures, galactomannan antigen and diagnostic imaging should be rigorously enforced.     

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.     

泊沙康唑的药动学及其药物相互作用

泊沙康唑为一新型三唑类抗真菌药,临床用于治疗和预防侵袭性真菌感染,具有高效、低毒、广谱的特点,并具有良好的耐受性,但对CYP3A4酶具有抑制作用,故可与多种药物发生药动学相互作用。本文综述了泊沙康唑的药动学特点及其药物相互作用,供临床参考,以促进临床安全合理用药。     

Triazole antifungal agents in invasive fungal infections: a comparative review

Invasive fungal disease continues to be a problem associated with significant morbidity and high mortality in immunocompromised and, to a lesser extent, immunocompetent individuals. Triazole antifungals have emerged as front-line drugs for the treatment and prophylaxis of many systemic mycoses. Fluconazole plays an excellent role in prophylaxis, empirical therapy, and the treatment of both superficial and invasive yeast fungal infections. Voriconazole is strongly recommended for pulmonary invasive aspergillosis. Posaconazole shows a very wide spectrum of activity and its primary clinical indications are as salvage therapy for patients with invasive aspergillosis and prophylaxis for patients with neutropenia and haematopoietic stem-cell transplant recipients. Itraconazole also has a role in the treatment of fungal skin and nail infections as well as dematiaceous fungi and endemic mycoses. Fluconazole and voriconazole are well absorbed and exhibit high oral bioavailability, whereas the oral bioavailability of itraconazole and posaconazole is lower and more variable. Posaconazole absorption depends on administration with a high-fat meal or nutritional supplements. Itraconazole and voriconazole undergo extensive hepatic metabolism involving the cytochrome P450 system. The therapeutic window for triazoles is narrow, and inattention to their pharmacokinetic properties can lead to drug levels too low for efficacy or too high for good tolerability or safety. This makes these agents prime candidates for therapeutic drug monitoring (TDM). Target drug concentrations for voriconazole and itraconazole should be >1?μg/mL and for posaconazole >1.5?μg/mL for treatment. Blood should be drawn once the patient reaches steady state, which occurs after 5 and 7 days of triazole therapy. Routine TDM of fluconazole is not required given its highly favourable pharmacokinetic profile and wide therapeutic index. The aim of this review is to provide a brief update on the pharmacology, activity, clinical efficacy, safety and cost of triazole agents (itraconazole, fluconazole, voriconazole and posaconazole) and highlight the clinical implications of similarities and differences.     

Posaconazole: a pharmacoeconomic review of its use in the prophylaxis of invasive fungal disease in immunocompromised hosts

Posaconazole (Noxafil?) is an oral, second-generation, extended-spectrum triazole whose approved indications include prophylaxis of invasive fungal disease (IFD) in immunocompromised patients. In pivotal head-to-head trials, posaconazole was significantly more effective in preventing IFD than standard azole therapy (i.e. oral fluconazole or itraconazole) in chemotherapy-induced neutropenic patients with acute myelogenous leukaemia (AML) or myelodysplastic syndromes (MDS) and was noninferior to treatment with fluconazole in patients with graft-versus-host disease (GVHD) who were receiving intensive immunosuppressive therapy following haematopoietic stem cell transplantation. In both indications, prophylactic posaconazole was associated with significantly lower rates of IFD-related mortality. The overall tolerability profile of posaconazole was generally similar to that of the other prophylactic treatments. The large body of modelled cost-effectiveness analyses from a healthcare payer perspective on the use of prophylactic posaconazole suggest that it is a dominant or cost-effective option relative to prophylaxis with standard azole therapy in neutropenic patients with AML/MDS, and fluconazole in patients with GVHD. Based on clinical trial data in these patient groups, antifungal prophylaxis with posaconazole was predicted to be a dominant or cost-effective option relative to prophylaxis with standard oral azoles, with regard to the incremental cost per QALY gained, life-year (LY) gained and/or other outcomes in cost-effectiveness analyses in numerous countries. In those analyses in which posaconazole did not dominate the comparator, posaconazole was considered cost effective, as the incremental cost per QALY or LY gained with posaconazole was lower than assumed willingness-to-pay thresholds. Sensitivity analyses consistently demonstrated that these results were robust to plausible changes in key model assumptions. In conclusion, prophylactic treatment with posaconazole is clinically effective in preventing IFD in neutropenic patients with AML/MDS and patients with GVHD. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of posaconazole as a dominant or cost-effective prophylactic antifungal treatment relative to prophylaxis with standard oral azoles in these patient populations at high risk of developing IFD.     

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.     

Pharmacologic and clinical evaluation of posaconazole

Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be a valuable pharmaceutical agent for the treatment of life-threatening fungal infections. This review will examine the development history of posaconazole and highlight the most recent advances.     

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.     

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.