micafungin and Candidiasis--Invasive

Invasive candidiasis is the most common fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay. The aim of this review was to evaluate and compare efficacy and safety of antifungal agents for the treatment of candidemia.. A systematic review with network meta-analysis (NMA), surface under the cumulative ranking analysis (SUCRA) and stochastic multicriteria acceptability analyses (SMAA) was performed (PROSPERO-CRD42020149264). Searches were conducted in PubMed and Scopus (Nov-2021). Randomised controlled trials evaluating the effect of oral antifungals (any dose or regimen) on mycological cure, discontinuation rates and adverse events were included.. Overall, 13 trials (n=3632) were analysed. There were no significant differences between therapies for the efficacy outcomes; however, caspofungin (50-150 mg), rezafungin (200-400 mg) and micafungin (100-150 mg) had higher rates of clinical and mycological responses (SUCRA overall response >60%) and were considered the most promising therapies. Fluconazole (400 mg) rated worst for overall response (17%). Rezafungin (200-400 mg) and micafungin (100 mg) were associated with lower discontinuation rates (<40%). Conventional amphotericin B (0.6-0.7 mg/kg) was more likely to be discontinued (odds ratio [OR] 0.08; 95% credibility interval [CrI] 0.00-0.95 vs. caspofungin 150 mg) and may impair liver function (87%).. Echinocandins are recommended as first-line treatments for invasive candidiasis following a priority order of caspofungin then micafungin. Rezafungin, an echinocandin under development, represents a potential option that should be further investigated. Azoles and liposomal amphotericin B can be used as second-line treatments in cases of fungal resistance or hypersensitivity.

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Caspofungin; Echinocandins; Humans; Lipopeptides; Micafungin; Network Meta-Analysis

Invasive candidiasis remains a leading cause of morbidity and mortality in various categories of patients at risk.. Structure and mechanism of action, pharmacokinetics and pharmacodynamics, clinical studies, safety, and regulatory status of micafungin are explored in the present review, focusing on pediatric patients younger than 4 months old.. Although limited, the available data on the efficacy and safety of micafungin in pediatric patients younger than 4 months old support its use for the treatment of invasive candidiasis in this particular population, in line with the most updated recommendations from the European Medicines Agency and the US Food and Drug Administration. Additional study, especially of high-dose micafungin, could further optimize the use of this drug in pediatric patients younger than 4 months old with

Topics: Antifungal Agents; Candidiasis, Invasive; Child; Echinocandins; Humans; Infant; Lipopeptides; Micafungin

Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC.. PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized controlled trials that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients. The primary outcome was treatment success with resolution of symptoms and signs, and absence of IC. In the meta-analysis a random effects model was used, and the odds ratio (OR) and 95% confidence intervals (CIs) were calculated.. Four randomized clinical trials (324 patients), 2 confirmed IC (micafungin vs. liposomal amphotericin B (L-AmB) and caspofungin vs. L-AmB) and 2 empirical therapy trials (caspofungin vs. deoxycholate amphotericin B and caspofungin vs. L-AmB) were included. There was no significant difference between echinocandins and comparator in terms of treatment success (OR = 1.61, 95% CI: 0.74-3.50) and incidence of treatment-related adverse events (OR = 0.70, 95% CI: 0.39-1.26). However, fewer children treated with echinocandins discontinued treatment because of adverse events than amphotericin B formulations (OR = 0.26, 95% CI: 0.08-0.82, P = 0.02).. In the treatment of IC in children, echinocandins show non-inferior efficacy compared with amphotericin B formulations with fewer discontinuations than in comparator arm.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Child; Child, Preschool; Deoxycholic Acid; Drug Combinations; Echinocandins; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Randomized Controlled Trials as Topic; Treatment Outcome

Micafungin is a selective inhibitor of the synthesis of fungal 1,3-β-D-glucan, an essential component of the fungal cell wall. It is available as a powder for infusion only and is registered for the treatment of invasive and esophageal candidiasis in addition to prophylaxis of Candida infections in both adults and children. Average exposure after a single intravenous 100 mg dose in healthy adults is 133 mg h/L. Both exposure and maximum plasma concentration show linear dose proportional pharmacokinetics (PK) over a 0.15-8 mg/kg dose range. In healthy adults, the clearance (CL) is 10.4 mL/h/kg and volume of distribution is 0.2 L/kg; both are independent of the dose. Micafungin is metabolized by arylsulfatase, catechol-O-methyltransferase, and several cytochrome P450 (CYP) isoenzymes (3A4, 1A2, 2B6 and 2C), but no dose adjustments are necessary in patients with (severe) hepatic dysfunction. Exposure to micafungin is lower in hematology patients, and is even further lowered in critically ill patients (including burn patients) compared with healthy volunteers, which might have consequences for treatment efficacy. In children, an increased CL has been reported: 40-80 mL/h/kg in premature neonates and 20 mL/h/kg in children >4 months of age. Therefore, relatively higher doses of 4-10 mg/kg in premature neonates and 2-4 mg/kg in children with invasive candidiasis are used. However, these higher CLs may also be explained by the eightfold higher free fraction of unbound micafungin in premature neonates, meaning that an augmented dose might not be required.

Topics: Adult; Antifungal Agents; Candidiasis; Candidiasis, Invasive; Child; Critical Illness; Dose-Response Relationship, Drug; Esophagitis; Humans; Infant; Infant, Newborn; Micafungin

Neonatal candidiasis causes significant morbidity and mortality in high risk infants. The micafungin dosage regimen of 10 mg/kg established for the treatment of neonatal candidiasis is based on a laboratory animal model of neonatal hematogenous Candida meningoencephalitis and pharmacokinetic (PK)-pharmacodynamic (PD) bridging studies. However, little is known about the how these PK-PD data translate clinically.. Micafungin plasma concentrations from infants were used to construct a population PK model using Pmetrics software. Bayesian posterior estimates for infants with invasive candidiasis were used to evaluate the relationship between drug exposure and mycologic response using logistic regression.. Sixty-four infants 3-119 days of age were included, of which 29 (45%) infants had invasive candidiasis. A 2-compartment PK model fits the data well. Allometric scaling was applied to clearance and volume normalized to the mean population weight (kg). The mean (standard deviation) estimates for clearance and volume in the central compartment were 0.07 (0.05) L/h/1.8 kg and 0.61 (0.53) L/1.8 kg, respectively. No relationship between average daily area under concentration-time curve or average daily area under concentration-time curve:minimum inhibitory concentration ratio and mycologic response was demonstrated (P > 0.05). Although not statistically significant, mycologic response was numerically higher when area under concentration-time curves were at or above the PD target.. While a significant exposure-response relationship was not found, PK-PD experiments support higher exposures of micafungin in infants with invasive candidiasis. More patients would clarify this relationship; however, low incidence deters the feasibility of these studies.

Topics: Antifungal Agents; Bayes Theorem; Candidiasis, Invasive; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Infant; Infant, Newborn; Male; Micafungin; Microbial Sensitivity Tests; Monte Carlo Method

Obesity is a worldwide epidemic associated with multiple comorbidities that increase the risk of hospitalization. Very little pharmacokinetic data are available for antifungal agents in obesity, as this population is often excluded from drug development studies and these agents are less commonly used than other antimicrobials. Systemic antifungal therapy for invasive candidiasis continues to have a high failure rate, and dose optimization in obesity provides an opportunity for improvement. Based on currently available data, some antifungals should be dosed based on total body weight (i.e. fluconazole), while others should not be adjusted for increased body weight (i.e. posaconazole). More studies are needed to determine if and when dosing changes are needed for many of the antifungal agents. Therefore, drug therapy regimens should be individually evaluated for dose optimization due to body weight.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Echinocandins; Fluconazole; Humans; Lipopeptides; Micafungin; Mycoses; Nitriles; Obesity; Pyridines; Triazoles

In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).

Topics: Anidulafungin; Antifungal Agents; Asia; Azoles; Candida; Candida albicans; Candida glabrata; Candida tropicalis; Candidemia; Candidiasis; Candidiasis, Invasive; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Incidence; Itraconazole; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Phenotype; Prevalence; Voriconazole

We describe a case of fungal tenosynovitis with Candida parapsilosis, which is an uncommonly reported agent causing tenosynovitis. It occurred in an immunocompetent individual, and the patient underwent an extensive noninfectious work-up for ongoing swelling and stiffness before being correctly diagnosed and treated. We emphasize the importance of considering atypical infections in the differential diagnoses in a patient presenting with indolent symptoms of tenosynovitis.

Topics: Antifungal Agents; Candida; Candidiasis, Invasive; Combined Modality Therapy; Echinocandins; Finger Injuries; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Tenosynovitis; Voriconazole

Invasive candidiasis is responsible for ∼ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over the last two decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking.. We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis.. Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Deoxycholic Acid; Drug Combinations; Echinocandins; Humans; Infant, Newborn; Lipopeptides; Micafungin; Triazoles

The time the earth takes to rotate its axis (the day) has dictated how often pharmaceutical compounds are dosed. The scientific link between the 2 events is materia medica arcana. As an example, in the treatment of invasive candidiasis, antifungal therapy with intravenous micafungin is dosed daily. A literature review revealed population pharmacokinetic analyses, in vivo pharmacokinetics/pharmacodynamics studies, and maximum-tolerated-dose studies of micafungin that examined optimal micafungin dosing strategies. The half-life of micafungin in patient blood was 14 hours in several studies, but was even longer in different organs, so that the concentration will persist above minimum inhibitory concentrations of Candida species for several days. Studies in mice and rabbits with persistent neutropenia and disseminated candidiasis, otherwise fatal, demonstrated that a single large dose of micafungin could clear disseminated candidiasis, even though the micafungin half-life in such animals is shorter than in humans. Human pharmacokinetics/pharmacodynamics studies confirmed this link between micafungin efficacy and the ratio of the area under the concentration-time curve, and the optimal exposures initially identified in neutropenic animals. Maximum tolerated dose studies have demonstrated safety of 900 mg administered daily for several weeks, whereas case reports demonstrate efficacy and safety of single 1400-mg doses. Thus, a single dose of micafungin, or 2 such doses within a few days of each other, is not only logical, but might even lead to faster clearance of Candida.

Topics: Animals; Antifungal Agents; Candida; Candidiasis, Invasive; Clinical Trials as Topic; Disease Models, Animal; Dose-Response Relationship, Drug; Echinocandins; Half-Life; Humans; Lipopeptides; Maximum Tolerated Dose; Micafungin; Mice; Microbial Sensitivity Tests; Rabbits

To evaluate the literature regarding the use of echinocandins to treat invasive fungal infections caused by Candida spp. in patients in the neonatal intensive care unit.. Literature retrieval was accessed through MEDLINE (Jan 2000-September 2011) using the search terms echinocandin, caspofungin, micafungin, anidulafungin, and neonate with limits for age group (ie, birth to 1 month). Reference citations from identified articles were also reviewed.. Relevant information on the pharmacokinetics, efficacy, and safety of echinocandins in neonates was selected. Prospective studies, retrospective studies, and case series in English identified from MEDLINE were evaluated.. Neonates, especially preterm neonates, have many risk factors that predispose them for invasive fungal infections caused by Candida spp. To date, the only antifungals recommended for use in neonates for treatment of candidiasis are amphotericin B (deoxycholate or a lipid formulation) and fluconazole; however, the toxicities associated with amphotericin B and resistance of certain Candida spp. to fluconazole limit their use in neonates. There is a need for a broad-spectrum antifungal agent with limited toxicity for use in this patient population. The echinocandins may represent such a class of antifungals. To date, micafungin is the most studied echinocandin in the neonatal population, followed by caspofungin; however, studies evaluating their efficacy and pharmacokinetic parameters in neonates are few.. Although studies suggest that the echinocandins may have a favorable safety profile, the lack of pharmacokinetic data and standardized study designs limit current recommendations of use of echinocandins as first-line agents in neonates in the treatment of fungal infections. However, if an echinocandin is to be used in this population, the data presented in this review suggest the use of micafungin over the other echinocandins, and higher doses of micafungin (10-15 mg/kg/day) should be used when central nervous system involvement is suspected.

Topics: Antifungal Agents; Candidiasis, Invasive; Caspofungin; Dose-Response Relationship, Drug; Echinocandins; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Lipopeptides; Micafungin; Treatment Outcome

Invasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients. Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus. We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.. We did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection. Seven trials involving 2913 patients were included in this analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.. Micafungin was associated with significantly better treatment success compared with the comparator antifungal agents (modified intention to treat, 2851 patients; random-effects model, OR 1.20, 95%CI 1.00 - 1.45, P = 0.0487). In addition, micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation (OR 1.47, 95%CI 1.08 - 2.00, P = 0.01). Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects (OR 0.94, 95%CI 0.77 - 1.11), fewer patients treated with micafungin withdrew from the studies because of adverse events (OR 0.64, 95%CI 0.44 - 0.94).. Micafungin has a good safety and tolerability profile, with an efficacy at least comparable to the other antifungal agents. Micafungin offers advantages over other agents for antifungal prophylaxis. Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

Topics: Antifungal Agents; Candidiasis, Invasive; Echinocandins; Humans; Lipopeptides; Micafungin; Randomized Controlled Trials as Topic; Treatment Outcome

Invasive Candida infections are a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Micafungin is a promising therapeutic option for treatment of invasive fungal infections in infants given its safety profile in older children and adults. Understanding micafungin safety in infants is particularly important because antifungals are most often used in premature infants with multiple underlying medical conditions in a critical care setting.. This article reviews the literature evaluating the safety profile of micafungin in infants and offers recommendations for optimal dosing for treatment of invasive candidiasis in the NICU setting. The review has been performed using a Medline search in September 2010 for related articles from 1990 to the present with the Mesh related terms 'micafungin' and 'safety' in combination with the free words 'antifungal', 'candidiasis', 'drug toxicity', 'infant, premature' and 'infant, newborn'.. Despite the limitations of the existing literature, we believe micafungin dosing of 10 mg/kg/day for all term and preterm infants is a viable treatment option in the NICU setting for management of invasive candidiasis. Although the number of infants for whom safety data are reported is small, higher doses of micafungin appear safe and well tolerated in this population.

Topics: Adult; Age Factors; Animals; Antifungal Agents; Candidiasis, Invasive; Child; Dose-Response Relationship, Drug; Echinocandins; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Lipopeptides; Micafungin

Micafungin is a semisynthetic lipopeptide developed from Coleophoma empetri, which blocks the synthesis of β-1,3-D-glucan, an essential component of the fungal wall, though non-competitive inhibition of β-1,3-D-glucan synthetase. Micafungin is a dose-dependent candidacidal agent with excellent in vitro efficacy against most Candida spp. including species resistant to amphotericin B, such as Candida lusitaniae, several azoles, such as C. glabrata or C. krusei, and isolates not susceptible to other echinocandins. Moreover, this drug is active against Candida biofilms. Micafungin is a first-line drug for the treatment of candidemias and invasive candidiasis in adults and children (including neonates). This drug is approved for use in the treatment of invasive candidiasis and Candida esophagitis, as well as in the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients or those at risk of prolonged neutropenia. Micafungin can be used both in the treatment and prevention of candidiasis in neonates, children, adolescents, adults, and the elderly, making it highly useful in patient groups in which the use of other antifungal drugs has not been authorized.

Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Biofilms; Candida; Candidiasis, Invasive; Cell Wall; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation, Preclinical; Echinocandins; Esophagitis; Fungal Proteins; Glucosyltransferases; Humans; Immunocompromised Host; Infant; Infant, Newborn; Lipopeptides; Micafungin; Mice; Middle Aged; Multicenter Studies as Topic; Postoperative Complications; Species Specificity; Transplantation; Young Adult

Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in various indications. They act as inhibitors of β-(1,3)-glucan synthesis in the fungal cell wall and have a favorable pharmacological profile. They have a broad spectrum of activity against all Candida species. Higher MIC's have been observed against C. parapsilosis and C. guilliermondii. Data from clinical trials for invasive Candida infections / candidaemia suggest that the clinical outcome of patients treated with either drug may be very similar. A comparison has been done between caspofungin and micafungin but for anidulafungin a comparative trial with another echinocandin is still lacking. All three drugs are highly effective if not superior to treatment with either fluconazole or Amphotericin B, particularly in well-defined clinical settings such as invasive Candida infections, Candida oesophagitis and candidaemia. Differences between the three echinocandins with regard to the route of metabolism, requirement for a loading dose, dose adjustment in patients with moderate to severe hepatic disease and different dosing schedules for different types of Candida infections have to be considered. Relevant drug-drug interactions of Caspofungin and Micafungin are minimal. Anidulafungin has no significant drug interactions at all. However, echinocandins are available only for intravenous use. All three agents have an excellent safety profile.

Topics: Anidulafungin; Antifungal Agents; Biofilms; Candidiasis, Invasive; Caspofungin; Drug Interactions; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Micafungin; Molecular Structure

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

Topics: Anidulafungin; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Echinocandins; Humans; Lipopeptides; MEDLINE; Micafungin

Working by a distinct cell wall-specific mechanism of action, the echinocandin class of antifungals has substantially expanded the range of available treatments for invasive Candida infections. Anidulafungin, caspofungin and micafungin were investigated versus drugs from earlier antifungal classes in large clinical trials that demonstrated their excellent clinical and microbiological efficacy in the primary treatment of invasive candidiasis. Therefore, and supported by a number of favourable pharmacological characteristics, the echinocandins rapidly became established in guidelines and clinical practice as primary treatment options for moderately to severely ill patients with invasive candidiasis. This article reviews the relevant clinical evidence that forms the basis for the use of echinocandins in the management of invasive candidiasis, and discusses their current role in the context of recent guideline recommendations and treatment optimization strategies.

Topics: Anidulafungin; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Clinical Trials as Topic; Drug Interactions; Echinocandins; Guidelines as Topic; Humans; Lipopeptides; Micafungin

Invasive fungal infections (IFIs) are one of the major reasons for morbidity and mortality in immunocompromised children. The majority of IFIs are caused by Candida and Aspergillus species. Early diagnosis and prompt initiation of appropriate antifungal therapy is essential for favorable outcome. Micafungin is a member of the echinocandins, a novel class of antifungal agents that target the biosynthesis of β-1,3-D-glucan, a key fungal cell wall component. It has concentration-dependent fungicidal activity against Candida species and fungistatic activity against Aspergillus species. Although optimal dosing of micafungin in children has not been established, the recommended dosage in children is 2 mg/kg/day (100 mg/day if >40 kg bodyweight) for invasive candidiasis, 1 mg/kg/day (50 mg/day if >40 kg bodyweight) for the prophylaxis of Candida infections in patients with anticipated prolonged and severe neutropenia or in allogeneic hematopoietic stem cell transplantation recipients. Micafungin has a favorable safety and drug-drug interaction profile. The most common adverse effects in children are diarrhea, epistaxis, abdominal pain, headache, nausea, vomiting, fever, chills, elevation of alanine aminotransferase/aspartate aminotransferase values, hypokalemia, thrombocytopenia, mucositis, and rash. Because of its different mechanisms of action, micafungin shows promise as part of the prophylactic and therapeutic management of IFIs, but larger prospective and comparative trials are needed for widespread use in children.

Topics: Adolescent; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis, Invasive; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Drug Dosage Calculations; Early Diagnosis; Echinocandins; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mycological Typing Techniques; Neutropenia; Transplantation, Homologous

Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study evaluated plasma levels, efficacy, and safety of micafungin at a dose of 8 mg/kg daily for a mean of 13.3 days (±5.2 days) in 35 neonates and young infants with IC. Micafungin plasma concentrations were 5.70 mg/liter preadministration and 17.23, 15.59, and 10.27 mg/liter after 1, 2, and 8 h, respectively. The resolution of the infection was achieved in 86.7% of patients treated for ≥14 days. In 20.0% of patients, we observed a transient hypertransaminasemia. Micafungin at a dose of 8 mg/kg daily is effective and well tolerated in neonates and young infants with IC. (This study has been registered at ClinicalTrials.gov under identifier NCT03421002 and in the EU Clinical Trials Register under number 2014-003087-20.).

Topics: Antifungal Agents; Candidiasis, Invasive; Echinocandins; Humans; Infant; Infant, Newborn; Lipopeptides; Micafungin

To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 μM·h) in >80% of the intended population.. In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment.. Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response.. The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.

Topics: Administration, Oral; Adult; Aged; Antifungal Agents; Candida; Candidiasis, Invasive; Echinocandins; Female; Fluconazole; Glycosides; Humans; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Triterpenes

Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (<500 neutrophils/μL) and without neutropenia. This pooled, post hoc analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d (paediatrics) with L-AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150 mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144); treatment duration 2-4 weeks (≤8 weeks for chronic disseminated candidiasis). Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment success, clinical and mycological response) were examined. Of 685 patients, 77 had neutropenia. The most common infection in patients with/without neutropenia was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall success was numerically lower in patients with vs without neutropenia (63.6% vs 72.9%). Clinical and mycological response was similar between groups. Neutropenia duration or Candida spp. did not impact micafungin's overall success rate. This analysis supports evidence that micafungin is effective against invasive candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia duration or Candida spp., although overall success may be lower than in patients without neutropenia.

Topics: Adolescent; Adult; Antifungal Agents; Candida; Candida albicans; Candida tropicalis; Candidemia; Candidiasis; Candidiasis, Invasive; Caspofungin; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Neutropenia; Treatment Outcome; Young Adult

Amphotericin B deoxycholate (AmB-D) is standard of care treatment for neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum fungicidal activity against Candida spp. We compared the efficacy and safety of intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA in infants >2-120 days of age with proven IC in a phase 3, randomized, double-blind, multicenter, parallel-group, noninferiority study (NCT00815516).. Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for ≥21 days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last study drug dose. MCA population pharmacokinetics included simulated area under the curve (AUC) at steady state and maximum plasma concentration after 2-hour infusion. AUC pharmacodynamic target exposure was 170 µg·h/mL.. Thirty infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence interval (CI): 36%-81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%-93%) AmB-D-group infants. The most common treatment-emergent adverse events were anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%) and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA was 399.3 ± 163.9 µg·h/mL (95% prediction interval: 190.3-742.3 µg/mL); steady state and maximum plasma concentration after 2-hour infusion was 31.1 ± 10.5 µg/mL (95% prediction interval: 17.0-49.7 µg/mL). MCA exposures were above the AUC pharmacodynamic target exposure.. Within the study limitations, infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both agents were safe and well tolerated.

Topics: Administration, Intravenous; Amphotericin B; Antifungal Agents; Area Under Curve; Candida; Candidiasis, Invasive; Deoxycholic Acid; Double-Blind Method; Drug Combinations; Female; Hematologic Tests; Humans; Infant; Infant, Newborn; Male; Micafungin; Treatment Outcome

In critically ill patients the incidence of invasive fungal infections caused by Candida spp. has increased remarkably. Echinocandins are recommended as initial treatment for invasive fungal infections. The safety and efficacy of micafungin compared to caspofungin is similar, but no comparison is made between anidulafungin and micafungin concerning safety and efficacy. We therefore performed a retrospective study to assess these aspects in critically ill patients with invasive candidiasis.. All patients in the intensive care unit (ICU) with invasive candidiasis, who were only treated with anidulafungin or micafungin, between January 2012 and December 2014 were retrospectively included. Baseline demographic characteristics, infection characteristics and patient courses were assessed.. A total of 63 patients received either anidulafungin (n = 30) or micafungin (n = 33) at the discretion of the attending intensivist. Baseline characteristics were comparable between the two groups, suggesting similar risk for developing invasive candidiasis. Patients with invasive candidiasis and liver failure were more often treated with anidulafungin than micafungin. Response rates were similar for both groups. No difference was observed in 28-day mortality, but 90-day mortality was higher in patients on anidulafungin. Multivariable cox regression analysis showed that age and serum bilirubin were the best parameters for the prediction of 90-day mortality, whereas APACHE II, Candida score and antifungal therapy did not contribute (P > 0.05). None of the patients developed impaired liver function related to antifungal use and no differences were seen in prothrombin time, serum transaminases and bilirubin levels between the groups, after exclusion of patients with liver injury or failure.. Micafungin can be safely and effectively used in critically ill patients with invasive candidiasis. The observed increased 90-day mortality with anidulafungin can be explained by intensivists unnecessarily avoiding micafungin in patients with liver injury and failure.

Topics: Anidulafungin; Antifungal Agents; APACHE; Candidiasis, Invasive; Critical Illness; Echinocandins; Female; Humans; Intensive Care Units; Lipopeptides; Liver; Liver Function Tests; Male; Micafungin; Middle Aged; Regression Analysis; Retrospective Studies; Treatment Outcome

Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome.. To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28.. Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs.. Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129).. The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia.. Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P = .008).. Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.. clinicaltrials.gov Idenitfier: NCT01773876.

Topics: Aged; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Candidiasis, Invasive; Critical Illness; Cross Infection; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Multiple Organ Failure; Time Factors

The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtained from four phase I and two phase III clinical trials. Population pharmacokinetic models were used to simulate the proportion of children who had a steady-state area under the concentration-time curve at 24 hours (AUC24) of micafungin within the 10th to 90th percentile range observed in a population of adults receiving a dose of micafungin with established efficacy for invasive candidiasis (100 mg/day), i.e., 75 to 139 μg·h/ml. Simulated pediatric dosages of 0.5 to 5 mg/kg of body weight/day were explored. A two-compartment model was used that incorporated body weight as a predefined covariate for allometric scaling of the pharmacokinetic parameters. During construction of the model, aspartate aminotransferase and total bilirubin were also identified as covariates that had a significant effect on micafungin clearance. A dose of 2 mg/kg resulted in the highest proportion of children within the predefined micafungin AUC24 target range for invasive candidiasis. Cutoffs of 40 or 50 kg for weight-based dosing resulted in heavier children being appropriately dosed. Thus, dose regimens of 1, 2, and 3 mg/kg/day micafungin are appropriate for the prevention of invasive candidiasis, the treatment of invasive candidiasis, and the treatment of esophageal candidiasis, respectively, in children aged 4 months to <17 years.

Topics: Adolescent; Antifungal Agents; Candidiasis; Candidiasis, Invasive; Child; Child, Preschool; Echinocandins; Female; Humans; Infant; Lipopeptides; Male; Micafungin

Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy.. This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression.. The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result.. This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC.. NCT01122368.

Topics: Adolescent; Adult; Aged; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Invasive; Double-Blind Method; Echinocandins; Female; Humans; Intensive Care Units; Intraabdominal Infections; Lipopeptides; Male; Micafungin; Middle Aged; Postoperative Complications; Pre-Exposure Prophylaxis; Proteoglycans; Young Adult

Micafungin demonstrated non-inferiority to caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in a major randomised clinical trial.. The aim of this study was to investigate if micafungin is a cost-saving option compared with caspofungin for treating candidaemia and IC.. A decision analytical model was constructed to capture downstream consequences of using either agent as initial therapy for candidaemia and IC. The main outcomes were treatment success and treatment failure (i.e. death, mycological persistence, emergent infection, clinical failure but microbiological success). Outcome probabilities and treatment pathways were derived from the literature. Cost inputs were from the latest Australian resources, and resource use was estimated by expert panel. The analysis was from the Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted.. Micafungin (AU$52 816) was associated with a lower total cost than caspofungin (AU$52 976), with a net cost-saving of $160 per patient. This was primarily due to the lower cost associated with alternative antifungal treatment in the micafungin arm. Hospitalisation was the main cost-driver for both arms. The model outcome was most sensitive to the proportion of treatment success in the micafungin arm. Uncertainty analysis demonstrated that micafungin had a 58% chance of being cost-saving compared with caspofungin.. Micafungin was cost-equivalent to caspofungin in treating candidaemia and IC, with variation in drug acquisition cost the critical factor.

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Echinocandins; Humans; Lipopeptides; Micafungin; Models, Economic; Treatment Outcome

Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida spp.. To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable or suspected invasive candidiasis.. Micafungin safety and pharmacokinetics were assessed in 2 phase I, open-label, repeat-dose trials. In Study 2101, children aged 2-16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10-14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical.. Safety was analyzed in 78 and 9 children in Studies 2101 and 2102, respectively. Although adverse events (AEs) were experienced by most children (2101: n=62; 2102: n=9), micafungin-related AEs were less common (2101: n=28; 2102: n=1), and the number of patients discontinuing due to AEs was low (2101: n=4; 2102: n=1). The most common micafungin-related AEs were infusion-associated symptoms, pyrexia and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults.. In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support US dosing recommendations in children.

Topics: Adolescent; Antifungal Agents; Body Weight; Candidiasis, Invasive; Child; Child, Preschool; Drug Administration Schedule; Echinocandins; Female; Humans; Infant; Kidney Function Tests; Lipopeptides; Liver Function Tests; Male; Micafungin

Micafungin (MCFG), an echinocandin antifungal agent, exhibits antifungal activity against Candida albicans and non-albicans Candida. The fungicidal activity of MCFG against clinical isolates of Candida species was investigated, and the clinical efficacy of MCFG in therapy of deep mycosis in surgery was studied using the AKOTT algorithm. The minimum inhibitory concentration and minimum fungicidal concentration values of fluconazole were ≤0.06-4 and >64 μg/ml, respectively, for each strain, whereas these values of MCFG were 0.008-0.5 and 0.016-1 μg/ml, suggesting that MCFG provided superior fungicidal ability against Candida albicans and non-albicans Candida. The subjects were separated into two groups: group A consisted of 20 subjects with both persisting fever refractory to broad-spectrum antibiotics and positive reaction to β-D-glucan test, and group B consisted of 20 subjects with either of those conditions. The overall response was evaluated as "effective" in 17 patients (85%) and 20 patients (100%) in groups A and B, respectively. In total, response was evaluated as "effective" in 37 patients (92.5%) and "ineffective" in 3 patients (7.5%). These findings suggest that MCFG administration should be used as empirical therapy for deep mycosis in surgically ill patients as it was shown to be an effective antifungal drug lacking serious adverse effects.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Candida; Candidiasis, Invasive; Cross Infection; Digestive System Neoplasms; Digestive System Surgical Procedures; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Surgical Wound Infection; Treatment Outcome

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Bacterial; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Chemical and Drug Induced Liver Injury; Early Diagnosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Mannans; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

The CLSI breakpoint for micafungin and Candida albicans is 0.25 mg/L, higher than the CLSI epidemiological cut-off value (0.03 mg/L) whereas the EUCAST values are identical (0.016 mg/L). We developed a novel in vitro dialysis-diffusion pharmacokinetic/pharmacodynamic (PK/PD) model, confirmed correlation to in vivo outcome and studied micafungin pharmacodynamics against Canida albicans.. Four C. albicans isolates, including a weak (F641L) and a strong (R647G) fks1 mutants, were studied using a 104 cfu/mL inoculum and RPMI medium with and without 10% pooled human serum. The exposure-effect relationship fAUC0-24/MIC was described for CLSI and EUCAST methodology. Monte Carlo simulation analysis included standard (100 mg i.v.) and higher (150-300 mg) doses q24h to determine the corresponding probability of target attainment (PTA).. The in vitro PK/PD targets for stasis/1-log kill were 36/57 fAUC0-24/MIC in absence and 2.8/9.2 fAUC0-24/MIC in the presence of serum, and similar for wild-type and fks mutant isolates. The PTAs for both PK/PD targets were high (>95%) for EUCAST susceptible isolates but not for CLSI susceptible non-wild-type isolates (CLSI MICs 0.06-0.25 mg/L). 300 mg q24h was needed to attain PK/PD targets for non-wild-type isolates with CLSI MICs 0.06-0.125 mg/L and EUCAST MICs 0.03-0.06 mg/L.. The in vitro 1-log kill effect corresponded to stasis in animal model and mycological response in patients with invasive candidiasis, thereby validating the model for studying pharmacodynamics of echinocandins in vitro. EUCAST breakpoints were well supported by our findings but our data questions whether the current CLSI breakpoint, which is higher than the epidemiological cut-off values, is appropriate.

Topics: Animals; Antifungal Agents; Candida; Candida albicans; Candidiasis, Invasive; Echinocandins; Humans; Micafungin; Microbial Sensitivity Tests

Invasive fungal infection, particularly intraabdominal candidiasis, exerts a negative impact on the outcome of pancreas transplant recipients (PTRs). Optimal antifungal prophylaxis in this context remains unclear.. We performed a single-centre retrospective study to compare the incidence of invasive candidiasis during the first 6 post-transplant months in a cohort of 218 PTRs over two periods in which different agents for antifungal prophylaxis were used: fluconazole (Fluco-Px) from March 1995 to June 2012, and micafungin followed by fluconazole (Mica-Px) from July 2012 to December 2018.. A total of 152 and 66 PTRs received Fluco-Px and Mica-Px. Mean age was 39.7 ± 7.8 years, 56.4% (123/218) were males, and 85.3% (186/218) underwent simultaneous pancreas-kidney transplantation. Invasive candidiasis occurred in 21.7% (33/152) of PTRs under Fluco-Px compared to 24.2% (16/66) of those under Mica-Px (p-value = .681). Median time from transplantation to infection was 8 days (interquartile range [IQR]: 6-16) under Fluco-Px versus 6.5 (IQR: 3.3-15.8) under Mica-Px (p-value = .623). Non-albicans Candida species comprised 27.5% (11/40) and 25.0% (4/16) of episodes under Fluco-Px and Mica-Px respectively (p-value = .849). Surgical site infection was the most common form in both groups (82.5% [33/40] and 87.5% [14/16]; p-value = .954). Multivariable analysis identified cold ischaemia time of the pancreas and kidney grafts, surgical reintervention and insulin requirement after transplantation as risks factor for invasive candidiasis.. This retrospective study did not reveal a significant benefit from the initial use of micafungin-based antifungal prophylaxis over fluconazole among PTRs in terms of invasive candidiasis.

Topics: Adult; Antifungal Agents; Candida; Candidiasis; Candidiasis, Invasive; Female; Fluconazole; Humans; Male; Micafungin; Middle Aged; Pancreas; Pancreas Transplantation; Retrospective Studies; Transplant Recipients

Since echinocandins are recommended as first line therapy for invasive candidiasis, detection of resistance, mainly due to alteration in FKS protein, is of main interest. EUCAST AFST recommends testing both MIC of anidulafungin and micafungin, and breakpoints (BPs) have been proposed to detect echinocandin-resistant isolates. We analyzed MIC distribution for all three available echinocandins of 2,787 clinical yeast isolates corresponding to 5 common and 16 rare yeast species, using the standardized EUCAST method for anidulafungin and modified for caspofungin and micafungin (AM3-MIC). In our database, 64 isolates of common pathogenic species were resistant to anidulafungin, according to the EUCAST BP, and/or to caspofungin, using our previously published threshold (AM3-MIC ≥ 0.5 mg/L). Among these 64 isolates, 50 exhibited 21 different FKS mutations. We analyzed the capacity of caspofungin AM3-MIC and anidulafungin MIC determination in detecting isolates with FKS mutation. They were always identified using caspofungin AM3-MIC and the local threshold while some isolates were misclassified using anidulafungin MIC and EUCAST threshold. However, both methods misclassified four wild-type C. glabrata as resistant. Based on a large data set from a single center, the use of AM3-MIC testing for caspofungin looks promising in identifying non-wild-type C. albicans, C. tropicalis and P. kudiravzevii isolates, but additional multicenter comparison is mandatory to conclude on the possible superiority of AM3-MIC testing compared to the EUCAST method.

Topics: Anidulafungin; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mutation

Candida auris is an emerging nosocomial pathogen worldwide. However, there has been little published on the management of C. auris in solid organ transplant recipients.. A single-center, retrospective cohort study was conducted to evaluate C. auris bloodstream infections in solid organ transplant recipients between January 2020 and December 2021. Patient-related and outcomes data were extracted from electronic medical records.. Of the 42 patients identified with C. auris bloodstream infections, five were in solid organ transplant recipients (1 heart, 3 liver, and 1 combined liver-kidney). The median time to fungemia from hospital admission was 43 days, and the median time to fungemia from transplant was 18 days. All patients received micafungin as initial treatment, at a median of 6 hours from pathogen detection. Four patients achieved blood clearance, two patients had persistent fungemia, and two patients developed secondary complications from hematogenous spread. One patient died, resulting in a mortality rate of 20%.. Solid organ transplant recipients are at high risk for developing C. auris bloodstream infections. In order to prevent graft loss and mortality, best practices for the management of C.auris should include rapid screening, diagnosis, and treatment. While echinocandins are considered first-line, antifungal selection should be based on susceptibilities and site of infection. Data to support routine use of combination therapy are lacking, however there may be a role for refractory cases. Prevention efforts against C. auris infection are especially important given the lack of effective decolonization strategies. For transplant recipients, hospitals should seek opportunities to restore patients' gut microbiome by curtailing unnecessary hospital procedures and inappropriate antimicrobial use. Further research and national guidelines are needed to better direct stewardship in this field.

Topics: Antifungal Agents; Candida; Candida auris; Candidiasis, Invasive; Echinocandins; Fungemia; Humans; Micafungin; Organ Transplantation; Retrospective Studies; Transplant Recipients

While the serological detection of (1→3)-β-D-glucan (BDG) can indicate invasive fungal disease (IFD), false positivity occurs. Nevertheless, the presence of BDG can still be recognized by the host's innate immune system and persistent BDG antigenemia, in the absence of IFD, can result in deleterious proinflammatory immune responses.. During the XXX (INTENSE) study into the preemptive use of micafungin to prevent invasive candidiasis (IC) after abdominal surgery, the serum burden of BDG was determined to aid diagnosis of IC. Data from the INTENSE study were analyzed to determine whether BDG was associated with organ failure and patient mortality, while accounting for the influences of IC and antifungal therapy.. A BDG concentration >100 pg/mL was associated with a significantly increased Sequential Organ Failure Assessment score (≤100 pg/mL: 2 vs >100 pg/mL: 5; P < .0001) and increased rates of mortality (≤100 pg/mL: 13.7% vs >100 pg/mL: 39.0%; P = .0002). Multiple (≥2) positive results >100 pg/mL or a BDG concentration increasing >100 pg/mL increased mortality (48.1%). The mortality rate in patients with IC and a BDG concentration >100 pg/mL and ≤100 pg/mL was 42.3% and 25.0%, respectively. The mortality rate in patients without IC but a BDG concentration >100 pg/mL was 37.3%. The use of micafungin did not affect the findings.. The presence of persistent or increasing BDG in the patient's circulation is associated with significant morbidity and mortality after abdominal surgery, irrespective of IC. The potential lack of a specific therapeutic focus has consequences when trying to manage these patients, and when designing clinical trials involving patients where host-associated BDG concentrations may be elevated.. NCT01122368.

Topics: beta-Glucans; Candidiasis, Invasive; Glucans; Humans; Micafungin; Prognosis; Sensitivity and Specificity

Pathogenesis of neonatal candidiasis (NC) is distinct from systemic candidiasis in adults and older pediatric patients due to the significant incidence of central nervous system involvement in neonates. Thus, although adequate and well-controlled trials in NC are often unfeasible due to difficulty enrolling patients, extrapolation of efficacy from antifungal drug trials in adults is generally not appropriate. However, treatment of NC is an area of great unmet need. We describe a regulatory review approach that combined the assessment of limited clinical efficacy, pharmacokinetics, and safety data from neonates and young infants along with microbiology outcomes and pharmacokinetic data from relevant nonclinical models of candidemia/invasive candidiasis to inform the use of micafungin in pediatric patients younger than 4 months, while communicating areas of remaining uncertainty in labeling.

Topics: Adult; Antifungal Agents; Candidiasis, Invasive; Humans; Infant; Infant, Newborn; Micafungin

Intra-abdominal candidiasis (IAC) is one of the most common yet underappreciated forms of invasive candidiasis. IAC is difficult to treat, and therapeutic failure and drug-resistant breakthrough infections are common in some institutions despite the use of echinocandins as first-line agents. Fosmanogepix (FMGX, formerly APX001) is a first-in-class antifungal prodrug that can be administered both intravenously and orally. FMGX is currently in phase 2 clinical development for the treatment of life-threatening invasive fungal infections. To explore the pharmacological properties and therapeutic potential of FMGX for IAC, we evaluated both drug penetration and efficacy of the active moiety manogepix (MGX, formerly APX001A) in liver tissues in a clinically relevant IAC mouse model infected with

Topics: Animals; Antifungal Agents; Candidiasis, Invasive; Echinocandins; Micafungin; Mice; Microbial Sensitivity Tests

The echinocandins anidulafungin (ANID) and micafungin (MICA) are recommended for treatment of invasive Candida infections. As target-site concentrations of antimicrobial agents are crucial for eradication of pathogens, we established and validated high-performance liquid chromatography-UV detection (HPLC-UV) assays for quantification of ANID and MICA in human plasma, ascites fluid, pleural effusion, and in cerebrospinal fluid (CSF). Sample pre-purification was performed by protein precipitation with acetonitrile followed by solid phase extraction. For both assays, intra- and interday precision, and accuracy fulfilled the requirements for bioanalytical methods issued by the European Medicine Agency (EMA). The lower limit of quantification was 0.01 mg/L for both drugs. At 25 °C, ANID and MICA concentrations declined by up to 70% within 24 h. Concentrations remained stable over 24 h at 4 °C and over four weeks at -80 °C. In conclusion, the developed methods are fit for the assessment of target-site pharmacokinetics of ANID and MICA in clinical studies.

Topics: Anidulafungin; Ascitic Fluid; Candidiasis, Invasive; Chromatography, High Pressure Liquid; Drug Monitoring; Humans; Limit of Detection; Linear Models; Micafungin; Reproducibility of Results; Solid Phase Extraction; Spectrophotometry, Ultraviolet

Invasive fungal infections (IFIs) contribute significantly to nosocomial illness in intensive care units (ICUs). Current practice guidelines recommend echinocandins, such as micafungin, for the treatment of invasive candidiasis. However, limited information on their use in real-world practice is available.. To describe the conditions of the use of micafungin in daily clinical practice and to evaluate its effectiveness and tolerability under real-world conditions.. This observational, prospective, multicentre study was performed in 34 ICUs in France. The study population consisted of 275 patients ≥16 years old who received treatment with micafungin during the inclusion period. Dose and duration of treatment were at the discretion of the physician.. Proven invasive candidiasis was documented before treatment in 106 patients (38.6%); 263 patients (95.6%) received the recommended dose (100 mg/day); 78 patients (28.8%) were treated for the recommended duration. A successful outcome was observed for 217 patients (79.2%). This proportion was significantly higher (83.3%; P < .0001) in patients treated for ≥14 days. Three patients discontinued treatment due to an adverse event considered related to micafungin. No clear impact of micafungin on hepatic function was observed.. Micafungin was effective in >75% of patients treated for IFIs in ICUs in France; outcomes may be improved with closer adherence to the recommended treatment duration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidiasis, Invasive; Female; France; Humans; Intensive Care Units; Invasive Fungal Infections; Male; Micafungin; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult

Infection with either mobilized colistin resistance-1 gene-positive gram-negative bacteria or invasive Candida lusitaniae occurs rarely throughout the United States. Here we report the existence of both invasive infections occurring in a single, complex patient who initially presented with necrotizing pancreatitis and gastrointestinal bleeding. We detail the patient's history and perioperative course for enterocutaneous fistulae takedown and ureteral stenting, describe a template of preventative steps taken in the perioperative environment to prevent nosocomial pathogen transmission, and provide a brief overview of both the mobilized colistin resistance-1 gene and C lusitaniae.

Topics: Candidiasis, Invasive; Cilastatin, Imipenem Drug Combination; Coinfection; Drug Resistance, Multiple, Bacterial; Gastrointestinal Hemorrhage; Humans; Intestinal Fistula; Klebsiella Infections; Klebsiella pneumoniae; Male; Micafungin; Middle Aged; Pancreatitis, Acute Necrotizing; Treatment Outcome; Vancomycin

Echinocandins are front-line agents for treatment of invasive candidiasis. There are no reported agent-specific differences in

Topics: Anidulafungin; Antifungal Agents; Candida glabrata; Candidiasis; Candidiasis, Invasive; Caspofungin; Drug Resistance, Fungal; Fungal Proteins; Gene Expression; Genetic Loci; Glucosyltransferases; Humans; Micafungin; Microbial Sensitivity Tests; Mutation Rate

Invasive fungal infections are responsible for significant morbidity and mortality. Safety and effectiveness of antifungal agents is a particular concern in pediatric populations, where data are often limited. Micafungin is an echinocandin with demonstrated antifungal activity against a wide spectrum of Candida spp.; this subanalysis of data from the MYRIADE study describes the use of micafungin and its therapeutic outcomes in pediatric patients, in normal clinical practice.. MYRIADE was an observational, multicenter, national, prospective, longitudinal study conducted from January 2010 to December 2012, in patients treated with micafungin using a prophylactic or curative strategy, across 17 sites [oncohematology (n = 8), neonatal intensive care units (ICUs) (n = 5) and pediatric ICUs (n = 4)]. The treatment regimen, the achievement of the therapeutic objective and the tolerance were reported.. The study population consisted of 110 pediatric patients (31 neonates, 24 children <2 years old and 55 children ≥2 to <16 years old). The therapeutic objective was achieved in 49/64 (76.6%) oncohematology patients, 28/29 (96.6%) neonatal ICU patients and 12/14 (85.7%) pediatric ICU patients. Twenty-four (21.8%) children developed an adverse event (AE); more AEs were observed in oncohematology patients compared with ICU patients [17 (26.1%) vs. 7 (15.6%)]. Only one serious AE, reported in an oncohematology patient, was considered related to micafungin.. In the first large observational study of micafungin treatment or prophylaxis conducted under real-world conditions in France, micafungin was effective and well tolerated for prophylaxis of invasive fungal infections in pediatric oncohematology patients and for curative purposes in pediatric and neonatal ICU patients.

Topics: Adolescent; Antifungal Agents; Candida; Candidiasis, Invasive; Chemoprevention; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; France; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Micafungin; Prospective Studies; Treatment Outcome

Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Databases, Factual; Echinocandins; Humans; Lipopeptides; Micafungin; Models, Economic; Treatment Outcome; Turkey

Guidelines on treating invasive candidiasis recommend initial treatment with a broad-spectrum echinocandin (e.g. micafungin), then switching to fluconazole if isolates prove sensitive (de-escalation strategy). This study aimed to evaluate the cost-effectiveness of de-escalation from micafungin vs escalation from fluconazole from a Chinese public payers perspective.. Cost-effectiveness was estimated using a decision analytic model, in which patients begin treatment with fluconazole 400 mg/day (escalation) or micafungin 100 mg/day (de-escalation). From Day 3, when susceptibility results are available, patients are treated with either fluconazole (if isolates are fluconazole-sensitive/dose-dependent) or micafungin (if isolates are resistant). The total duration of (appropriate) treatment is 14 days. Model inputs are early (Day 3) and end-of-treatment mortality rates, treatment success rates, and health resource utilization. Model outputs are costs of health resource utilization over 42 days, incremental cost per life-year, and incremental cost per quality-adjusted life-year (QALY) over a lifetime horizon.. In the base-case analysis, the de-escalation strategy was associated with longer survival and higher treatment success rates compared with escalation, at a lower overall cost (-¥1,154; -175 United States Dollars). Life-years and QALYs were also better with de-escalation. Thus, this strategy dominated the escalation strategy for all outcomes. In a probabilistic sensitivity analysis, 99% of 10,000 simulations were below the very cost-effective threshold (1 × gross domestic product).. The main limitation of the study was the lack of real-world input data for clinical outcomes on treatment with micafungin in China; data from other countries were included in the model.. A de-escalation strategy is cost-saving from the Chinese public health payer perspective compared with escalation. It improves outcomes and reduces costs to the health system by reducing hospitalization, due to an increase in the proportion of patients receiving appropriate treatment.

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Echinocandins; Fluconazole; Humans; Lipopeptides; Micafungin; Survival

Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI.. This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III).. Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed.. Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Cohort Studies; Drug Resistance, Fungal; Female; Fluconazole; Gestational Age; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Male; Micafungin; Microbial Sensitivity Tests; Neurodevelopmental Disorders; Prospective Studies; Sepsis; Treatment Outcome

Delay in treatment of candidaemia and invasive candidiasis remains a cause of significant morbidity and mortality in high-risk patients. Widespread empirical utilization of antifungal therapy often occurs in an effort to minimize this risk.. This study assessed the impact of the T2Candida Panel in a multi-hospital community health system on time to initiation of antifungal therapy in candidaemic patients as well as the utilization of micafungin.. Outcomes were compared between those patients with candidaemia prior to T2Candida implementation and those after implementation. Micafungin utilization for patients with suspected candidaemia/invasive candidiasis was compared with that for patients with a negative T2Candida Panel post-implementation.. There was a significant decrease in time to appropriate therapy in the post-T2Candida group (34 versus 6 h, P = 0.0147). Empirical antifungal therapy was avoided in 58.4% of T2Candida-negative patients.. These results support the implementation of T2Candida to improve time to appropriate therapy for candidaemic patients while simultaneously expanding antimicrobial stewardship efforts to appropriately utilize antifungals.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Antimicrobial Stewardship; Candida; Candidemia; Candidiasis, Invasive; Community Health Centers; Female; Humans; Male; Micafungin; Middle Aged; Retrospective Studies

Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.

Topics: Amphotericin B; Antifungal Agents; Candidemia; Candidiasis, Invasive; Cost-Benefit Analysis; Decision Support Techniques; Humans; Micafungin; Treatment Outcome; Turkey

Currently echinocandins are recommended in Candida peritonitis and pleuritis. We determined micafungin killing rates (k values) at therapeutic concentrations (0.25-2 mg/L) in RPMI-1640 with and without 10 and 30% serum mimicking in vivo conditions against six Candida species isolated from peritoneal and pleural fluid. In RPMI-1640, micafungin was fungicidal against C. glabrata, C. krusei and C. kefyr within 2.27 ± 10.68, 2.69 ± 10.29 and 3.10 ± 4.41 h, respectively, while was fungistatic against C. albicans, C. tropicalis and C. parapsilosis. In 10% serum, ≥ 0.25, ≥ 0.5, ≥ 0.5 and ≥ 1 mg/L micafungin produced positive k values (killing) for all C. albicans, C. glabrata, C. kefyr and C. krusei, respectively. In 30% serum, 2 mg/L micafungin produced killing against all C. albicans, C. glabrata and C. kefyr isolates, but was ineffective against C. krusei, C. parapsilosis and 2 of 3 C. tropicalis. Micafungin exposure should be increased against non-albicans species to eradicate fungi from peritoneal and pleural cavities.

Topics: Antifungal Agents; Candida; Candidiasis, Invasive; Humans; Micafungin; Microbial Sensitivity Tests; Microbial Viability; Peritoneal Cavity; Pleural Cavity

Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively.. A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan's healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted.. For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment.. Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan.

Topics: Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candidemia; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Echinocandins; Economics, Pharmaceutical; Fluconazole; Humans; Lipopeptides; Micafungin; Taiwan; Treatment Outcome

Echinocandins are an important class of antifungal agents in the treatment of invasive candidiasis. However, little is known about the metabolomic effects of echinocandins on Candida . We therefore performed LC-high-resolution MS (LC-HRMS)-based metabolomics profiling of the response of Candida albicans cells to increasing concentrations of micafungin to determine the metabolic response of Candida to micafungin subinhibitory injury.. Isolates of C. albicans were cultured on nitrocellulose filters to mid-logarithmic phase of growth and micafungin (0-0.25 mg/L) was added. At mid-logarithmic phase, replicates were metabolically quenched. Intracellular metabolites were analysed by LC-HRMS. Changes in pool sizes of individual metabolites were analysed by Student's t -test adjusted for multiple hypothesis testing by Benjamini-Hochberg correction. Metabolites were ascribed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways database.. Among 3446 detected metabolites, 204 were identified by comparison against pure standard or comparison against a library of mass-retention-time pairs. Fifty had significantly altered abundances in response to increasing micafungin concentrations. Pool sizes of amino acids, nucleic acids and polyamine metabolism were significantly increased at subinhibitory concentrations, while exposure to inhibitory concentrations resulted in a precipitous decrease consistent with fungicidal activity.. Micafungin induces a re-routing of metabolic pathways inhibiting protein synthesis and cell replication. These results shed light on new mechanisms of action of echinocandins.

Topics: Amino Acids; Antifungal Agents; Candida albicans; Candidiasis; Candidiasis, Invasive; Carbon; Chromatography, Liquid; Echinocandins; Lipopeptides; Mass Spectrometry; Metabolic Networks and Pathways; Metabolomics; Micafungin; Microbial Sensitivity Tests; Nucleic Acids

We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital.. The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay.. SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P  <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P  <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment.. Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin.

Topics: Antifungal Agents; Biofilms; Candida; Candida albicans; Candida glabrata; Candidiasis; Candidiasis, Invasive; Echinocandins; Glucosyltransferases; Glycosides; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Triterpenes

Combination therapy may be an alternative therapeutic approach for difficult-to-treat Candida infections with the aim of increasing efficacy of antifungal therapy. Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or polyenes for the treatment of invasive candidiasis has not been studied. We used Bliss independence drug interaction analysis and time-kill assays to examine the in vitro interactions of isavuconazole with amphotericin B or micafungin, an echinocandin, against strains of Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, and Candida krusei. The Bliss independence-based drug interactions modeling showed that the combination of isavuconazole and micafungin resulted in synergistic interactions against C. albicans, C. parapsilosis, and C. krusei. The degree of synergy ranged from 1.8% to 16.7% (mean %ΔΕ value) with the highest synergy occurring against C. albicans (⊙SYN% = 8.8%-110%). Time-kill assays showed that the isavuconazole-micafungin combination demonstrated concentration-depended synergy against C. albicans and C. parapsilosis. The combined interaction by Bliss analysis between isavuconazole and amphotericin B was indifferent for C. albicans, C. parapsilosis, and C. tropicalis while for C. glabrata was antagonistic (-2% to -6%) and C. krusei synergistic (3.4% to 7%). The combination of isavuconazole-amphotericin B by time-kill assay was antagonistic against C. krusei and C. glabrata. Collectively, our findings demonstrate that combinations of isavuconazole and micafungin are synergistic against Candida spp., while those of isavuconazole and amphotericin B are indifferent in vitro.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis, Invasive; Drug Synergism; Echinocandins; In Vitro Techniques; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Nitriles; Pyridines; Time Factors; Triazoles

Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

Topics: Administration, Intravenous; Adult; Aged; Anidulafungin; Antifungal Agents; Candidiasis, Invasive; Caspofungin; Critical Illness; Echinocandins; Female; Fluconazole; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Middle Aged; Multivariate Analysis; Retrospective Studies

Topics: Administration, Intravenous; Antifungal Agents; Candida albicans; Candidiasis, Invasive; Cerebrospinal Fluid Shunts; Echinocandins; Humans; Infant, Newborn; Infant, Premature; Lipopeptides; Male; Meningitis, Fungal; Micafungin

The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre. Essential agreement and categorical agreement (CA) were assessed using the reference method. Of the 34 total blood isolates collected, Candida albicans comprised only 38 % (13) of the Candida spp. with Candidaglabrata being nearly as prevalent (29 %, 10). CA using Etest was 86 % for fluconazole, 72 % for caspofungin, 98 % for micafungin and 97 % for anidulafungin. Vitek 2 CA was 90 % for fluconazole and 98 % for caspofungin. Sensititre CA was 93 % for fluconazole, 98 % for caspofungin, 98 % for micafungin and 100 % for anidulafungin. Although our study tested a small population of Candida isolates, our results were variable by method. When implementing antifungal susceptibility testing, clinicians should be aware of the strengths and limitations of each testing method.

Topics: Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candidiasis; Candidiasis, Invasive; Caspofungin; Drug Resistance, Fungal; Echinocandins; Fluconazole; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Respiratory System; Urine

Topics: Adolescent; Adult; Aged; Antifungal Agents; Burns; Candidiasis, Invasive; Critical Care; Critical Illness; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Wound Infection; Young Adult

Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs).. A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome.. 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009).. High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

Topics: Adult; Aged; Candidiasis, Invasive; Critical Care; Cross Infection; Diagnosis-Related Groups; Echinocandins; Female; Fungemia; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Lipopeptides; Male; Micafungin; Middle Aged; Multiple Organ Failure; Mycoses; Postoperative Complications; Retrospective Studies; Severity of Illness Index; Shock, Septic; Spain; Treatment Outcome

Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized.. Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC.. 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89).. Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candida albicans; Candida glabrata; Candidiasis; Candidiasis, Invasive; Carrier State; Caspofungin; Critical Care; Echinocandins; Female; Fluconazole; Humans; Incidence; Intensive Care Units; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Sensitivity and Specificity; Singapore; Tertiary Care Centers; Voriconazole

Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines.. Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources.. The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success.. European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness.. From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

Topics: Anidulafungin; Antifungal Agents; Candidemia; Candidiasis, Invasive; Caspofungin; Cost-Benefit Analysis; Drug Costs; Echinocandins; Fluconazole; Humans; Intensive Care Units; Length of Stay; Lipopeptides; Micafungin; Models, Economic; Treatment Outcome; United Kingdom

Echinocandins are N-acyl-substituted cyclic hexapeptides with potent in vitro and in vivo activity against Candida species that are used for primary treatment and prevention of candidemia and invasive candidiasis. Recent progress in the translational research of echinocandins has led to new approaches for treatment of central venous catheter Candida biofilms. Other studies have laid the experimental and clinical foundation for use of extended dosing intervals for administration of echinocandins in treatment and prevention of candidemia and invasive candidiasis.

Topics: Antifungal Agents; Biofilms; Candida; Candidemia; Candidiasis; Candidiasis, Invasive; Caspofungin; Catheter-Related Infections; Echinocandins; Humans; Lipopeptides; Micafungin; Translational Research, Biomedical

The current standard of treatment of invasive candidiasis with echinocandins requires once-daily therapy. To improve quality of life, reduce costs, and improve outcome, we studied the pharmacokinetics (PK), efficacy, and safety of alternate dosing regimens of micafungin (MFG) for the treatment of experimental subacute disseminated candidiasis.. MFG was administered for 12 days starting 24 hours after intravenous inoculation of 1 × 10(3) Candida albicans blastoconidia. Study groups consisted of MFG at 1 mg/kg every 24 hours (MFG1), 2 mg/kg every 48 hours (MFG2), and 3 mg/kg every 72 hours (MFG3), and untreated controls. PK of MFG were determined on day 7 by high-performance liquid chromatography and modeled using nonparametric adaptive grid program. A 2-compartment PK model with volume of the central compartment (Vc), clearance (SCL), and the intercompartmental rate constants Kcp and Kpc was used. The fungal burden in 7 tissues was determined 312 hours after the initiation of therapy.. PK of MFG were linear and the parameter means ± SD were Vc = 0.41 ± 0.18 L, Kcp = 2.80 ± 1.55/hour, Kpc = 1.71 ± 0.93/hour, and SCL = 0.16 ± 0.003 L/hour (r(2) = 0.99). The area under the plasma drug concentration - time curve for MFG1, MFG2, and MFG3 was 198.7 ± 19.8, 166.3 ± 36.7, and 192.8 ± 46.2 mg × hour/L, respectively (P = .24). All treatment groups showed significant and comparable resolution of (1→3)-β-D-glucan levels and clearance of C. albicans from liver, spleen, kidney, brain, lung, vitreous humor, and vena cava in comparison to untreated controls (P ≤ .05). There were no differences in hepatic or renal function among study groups.. Less fractionated MFG regimens of every 48 and 72 hours are safe and as effective in experimental disseminated candidiasis as once-daily therapy in neutropenic hosts.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis; Candidiasis, Invasive; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Echinocandins; Female; Lipopeptides; Micafungin; Neutropenia; Proteoglycans; Rabbits

This study aimed to investigate the cumulative fraction of response of various echinocandin (caspofungin, micafungin and anidulafungin) dosing regimens against Candida spp. in paediatric patients with invasive fungal infections (IFIs). Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the ability of each echinocandin regimen in terms of fAUC/MIC (free drug area under the concentration-time curve/minimum inhibition concentration ratio) targets of caspofungin, micafungin and anidulafungin. Pharmacodynamic targets were attained in paediatric patients by both caspofungin regimens as well as by a high micafungin dosing regimens against Candida albicans and Candida glabrata. However, the results for anidulafungin suggested that the dosing regimens recommended were not optimal for paediatric patients. In addition, the predicted efficacy of all of the echinocandins against Candida parapsilosis was low. This is the first study to assess caspofungin, micafungin and anidulafungin therapy using Monte Carlo simulation. These results rationalise and optimise the dosage regimens of caspofungin, micafungin and anidulafungin against C. albicans, C. glabrata and C. parapsilosis for paediatric patients with IFIs.

Topics: Adolescent; Adult; Anidulafungin; Antifungal Agents; Candida; Candidiasis, Invasive; Caspofungin; Child; Child, Preschool; Dose-Response Relationship, Drug; Echinocandins; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Monte Carlo Method

The incidence of invasive candidiasis caused by non-albicans Candida (NAC) spp. is increasing. The aim of this analysis was to evaluate the efficacy of micafungin, caspofungin and liposomal amphotericin B in patients with invasive candidiasis and candidaemia caused by different Candida spp. This post hoc analysis used data obtained from two randomised phase III trials was conducted to evaluate the efficacy and safety of micafungin vs. caspofungin and micafungin vs. liposomal amphotericin B. Treatment success, clinical response, mycological response and mortality were evaluated in patients infected with C. albicans and NAC spp. Treatment success rates in patients with either C. albicans or NAC infections were similar. Outcomes were similar for micafungin, caspofungin and liposomal amphotericin B. Candida albicans was the most prevalent pathogen recovered (41.0%), followed by C. tropicalis (17.9%), C. parapsilosis (14.4%), C. glabrata (10.4%), multiple Candida spp. (7.3%) and C. krusei (3.2%). Age, primary diagnosis (i.e. candidaemia or invasive candidiasis), previous corticosteroid therapy and Acute Physiology and Chronic Health Evaluation II score were identified as potential predictors of treatment success and mortality. Micafungin, caspofungin and liposomal amphotericin B exhibit favourable treatment response rates that are comparable for patients infected with different Candida spp.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidemia; Candidiasis, Invasive; Caspofungin; Clinical Trials, Phase III as Topic; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Survival Analysis; Treatment Outcome; Young Adult

The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.

Topics: Adenine Nucleotides; Adult; Anidulafungin; Antibiotic Prophylaxis; Antifungal Agents; Antimetabolites, Antineoplastic; Arabinonucleosides; Candida; Candidiasis, Invasive; Caspofungin; China; Clofarabine; Cohort Studies; Cross Infection; Echinocandins; Fusariosis; Fusarium; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Lung Diseases, Fungal; Micafungin; Retrospective Studies; Risk Factors

To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH).. Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions.. Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ± 15.87 versus 71.31 ± 14.24; P = 0.008) and Day 2 (119.01 ± 27.20 versus 104.54 ± 21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis.. There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.

Topics: Aged; Aged, 80 and over; Antifungal Agents; Candida; Candidiasis, Invasive; Critical Illness; Echinocandins; Female; Hemofiltration; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method

Topics: Adolescent; Antifungal Agents; Candidiasis, Invasive; Echinocandins; Humans; Lipopeptides; Maintenance Chemotherapy; Male; Micafungin

The response rate among 58 patients with cancer and candidemia or deep-seated candidiasis treated with micafungin monotherapy was 81%. Intensive care unit (ICU) stay, concomitant nonfungal infections, and acute kidney injury were significantly associated with the 30-day crude mortality rate. Severe neutropenia was an independent predictor of micafungin failure. The efficacy and safety of micafungin in cancer patients with invasive candidiasis were comparable to those reported for patients without malignancy and for cancer patients treated with caspofungin.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidemia; Candidiasis; Candidiasis, Invasive; Echinocandins; Female; Humans; Intensive Care Units; Lipopeptides; Male; Micafungin; Middle Aged; Neoplasms; Neutropenia; Young Adult

A multicenter observational study was conducted in Italy to assess the safety of micafungin in the daily clinical practice for the treatment of proven and suspected invasive candidiasis (IC), as well as to describe rates of clinical response to micafungin treatment.. From October 2010 to March 2012, data from consecutive eligible neonate, pediatric, and adult patients treated with micafungin for a proven or suspected IC were collected. Patients were deemed as eligible if they or their parents signed an informed consent. The study endpoints were to assess safety of micafungin in the treatment of both proven and suspected IC, and to describe rates of clinical response to micafungin treatment. Clinical response was assessed at the end of micafungin treatment (EOMT) and defined as favorable (complete or partial resolution of signs and symptoms) or unfavorable (stability or progression).. During the study period, 108 patients with proven or suspected IC were enrolled. Thirty-six out of 108 patients (33%) were < 18 year-old (median 1 year), whereas 72 (67%) were ≥ 18 year-old (median 71 years). Neonates in NICU accounted for 36% of pediatric patients, with the majority of them (54%) being extremely low birth weight (ELBW) newborns. Fifty-eight out of 108 patients (54%) received micafungin for a proven IC, whereas 50/108 patients (46%) were treated for a suspected IC. Among proven IC, candidemia accounted for the majority of events (54/58, 93%), with Candida albicans (35/58, 60%) as the most frequently isolated species. Therapy was discontinued due to occurrence of an adverse event in 4/108 subjects (4%). No pediatric patient had treatment interruption because of adverse events. A 67% favorable response rate was observed at EOMT. No age-, species-, underlying conditions- or ward-related differences of favorable response were observed. Survival at EOMT was 90% (97/108 patients), with rates of 97% (35/36) and 86% (62/72) among children and adults, respectively.. Micafungin was well tolerated in a heterogeneous real world population with a bimodal age distribution. A high rate of favorable response to micafungin treatment was reported in both proven and suspected IC.

Topics: Adolescent; Adult; Aged; Antifungal Agents; Candidiasis, Invasive; Child; Child, Preschool; Echinocandins; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Prospective Studies; Treatment Outcome

Micafungin was non-inferior to liposomal amphotericin B (LAmB) for the treatment of candidaemia and invasive candidiasis (IC) in a major clinical trial. The present study investigated the economic impact of micafungin vs. LAmB in treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using micafungin or LAmB as primary definitive therapy. The main outcomes were treatment success and treatment failure due to mycological persistence, or death. Outcome probabilities were derived from key published sources. Resource used was estimated by an expert panel and cost inputs were from the latest Australian resources. The analysis was from an Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$61 426) had a lower total cost than LAmB (AU$72 382), with a total net cost-saving of AU$10 957 per patient. This was primarily due to the lower cost associated with initial antifungal treatment and shorter length of stay for patients in the micafungin arm. Hospitalisation was the main cost driver for both arms. Results were robust over a wide range of variables. The uncertainty analysis demonstrated that micafungin had a 99.9% chance of being cost-saving compared with LAmB. Micafungin was associated with cost-saving relative to LAmB in the treatment of candidaemia and IC in Australia.

Topics: Amphotericin B; Antifungal Agents; Australia; Candidemia; Candidiasis, Invasive; Echinocandins; Health Care Costs; Humans; Lipopeptides; Micafungin; Treatment Outcome

Although micafungin pharmacokinetic values were comparable between younger (<5 years) and older children (≥5 years) with candidemia and invasive candidiasis, younger children had a lower peak plasma micafungin concentration, lower micafungin exposure and larger micafungin clearance. Half-life remained unchanged with repeated dosing. Metabolite plasma concentrations remained low in older children; however, metabolite M-5 concentrations were higher in younger children.

Topics: Adolescent; Age Factors; Antifungal Agents; Candidemia; Candidiasis, Invasive; Child; Child, Preschool; Echinocandins; Female; Humans; Infant; Lipopeptides; Male; Metabolic Clearance Rate; Micafungin

Topics: Antifungal Agents; Candidemia; Candidiasis, Invasive; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin

Echinocandins are a preferred therapy for invasive candidiasis due to their potency and broad spectrum. Resistance, especially in Candida glabrata, is an emerging threat to their use. Pharmacodynamic (PD) studies examining reduced susceptibility secondary to fks mutations in C. glabrata are lacking. The current study explored PD targets for anidulafungin, caspofungin, and micafungin in an in vivo invasive candidiasis model against 11 C. glabrata isolates with known or putative fks mutations. The PD targets were compared to those of 8 wild-type (WT) isolates. The MIC ranges in the WT group were 0.03 to 0.25 mg/liter for anidulafungin, 0.03 to 0.25 mg/liter for caspofungin, and 0.01 to 0.06 mg/liter for micafungin. The MIC ranges for mutants were 0.06 to 4, 0.25 to 16, and 0.13 to 8 mg/liter for the same compounds, respectively. The mean free drug 24-h area under the concentration-time curve (AUCf)/MIC ratio associated with a stasis endpoint for the WT group was 13.2 for anidulafungin, 2.04 for caspofungin, and 6.78 for micafungin. Comparative values for mutants were 3.43, 2.67, and 0.90, respectively. Pharmacokinetic data from patients suggest that the C. glabrata PD targets needed for success in this model could be achieved based on MIC values of 0.25 mg/liter for anidulafungin, 2 mg/liter for caspofungin, and 0.5 mg/liter for micafungin. These values are higher than recently identified epidemiology cutoff values (ECVs). The results suggest that drug-specific MIC breakpoints could be increased for caspofungin and micafungin against C. glabrata and could include organisms with mutations in fks-1 and fks-2. While identification of genetic mutants is epidemiologically important, the phenotype (MIC) provides a better predictor of therapeutic efficacy.

Topics: Anidulafungin; Animals; Antifungal Agents; Area Under Curve; Candida glabrata; Candidiasis, Invasive; Caspofungin; Echinocandins; Female; Fungal Proteins; Glucosyltransferases; Humans; Kidney; Lipopeptides; Male; Micafungin; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mutation

Echinocandins are a new class of antifungal agents with a specific mechanism of action. These drugs inhibit the enzyme 1,3β-D-glucan synthetase which is responsible for the formation of 1,3β-D-glucan, an essential fungal cell wall component. They have a good activity against Candida species and Aspergillus. Three agents are available at the present time or under development : caspofungin, micafungin and anidulafungin. These drugs require intravenous administration. Efficacy, safety, rare drugs interactions and specificity of action are advantages for therapy of invasive fungal infections. In France, micafungin and caspofungin are approved for a pediatric use.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; Aspergillus; Candidiasis, Invasive; Caspofungin; Child; Echinocandins; Evidence-Based Medicine; Humans; Injections, Intravenous; Lipopeptides; Micafungin; Mycoses; Treatment Outcome