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Expert Review of Anti-infective Therapy Apr 2022Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous meningoencephalitis. The echinocandins... (Review)
Review
INTRODUCTION
Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous meningoencephalitis. The echinocandins including micafungin have emerged as a preferred agent in most cases of candidemia and invasive candidiasis but data in pediatric patients under 4 months of age are limited.
AREAS COVERED
In this report, we review the micafungin use in infants younger than 4 months of age. Animal studies as well as clinical data that support its use in neonatal candidiasis are reviewed. In addition, the status of FDA approval and the rationale of micafungin dosing recommendations in infants <4 months are discussed.
EXPERT OPINION
A dose of 4 mg/kg was approved for treatment of candidemia, peritonitis and abscesses excluding meningoencephalitis or ocular involvement in patients younger than 4 months of age. However, because of the risk of central nervous system dissemination as well as the difficulty in establishing this diagnosis, this dose is inadequate to treat ill infants with candidemia. More studies are needed to establish the safety and efficacy of micafungin daily dose of at least 10 mg/kg in infants younger than 4 months of age when hematogenous meningoencephalitis or ocular involvement cannot be excluded.
Topics: Animals; Antifungal Agents; Candida; Candidemia; Candidiasis; Candidiasis, Invasive; Child; Echinocandins; Humans; Lipopeptides; Meningoencephalitis; Micafungin
PubMed: 34882043
DOI: 10.1080/14787210.2022.2013807 -
The Journal of Infection Jun 2014Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with neutropenia and those undergoing bone marrow or... (Review)
Review
Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with neutropenia and those undergoing bone marrow or stem cell transplants. Micafungin is an echinocandin antifungal drug with activity against all major Candida spp. Currently, micafungin is indicated for treatment of invasive candidiasis, oesophageal candidiasis and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia. Micafungin demonstrates in vitro and in vivo activity against Aspergillus spp. It is currently not licensed to treat Aspergillus infections in the UK or USA. This review summarises the current evidence base surrounding the clinical use of micafungin in the treatment of invasive aspergillosis to consider the potential role of micafungin in these patients. There are currently no randomised studies comparing micafungin with standard antifungal therapy. Prospective non-randomised clinical studies, predominantly performed in Japan, involving 492 patients with aspergillosis and 455 febrile patients with chemotherapy-induced neutropenia suggest that micafungin may be as effective as comparator antifungal agents. Other clinical evidence is limited to case reports. Further experience in the form of randomised controlled trials is required to establish the exact role of micafungin in the context of currently available broad-spectrum antifungal agents.
Topics: Antifungal Agents; Clinical Trials as Topic; Echinocandins; Humans; Invasive Pulmonary Aspergillosis; Lipopeptides; Micafungin; Prospective Studies; Treatment Outcome
PubMed: 24480373
DOI: 10.1016/j.jinf.2014.01.007 -
The Journal of Clinical Endocrinology... Apr 2019Patients with type 1 diabetes mellitus (T1DM) are insulin dependent. Infection increases insulin resistance and subsequently increases insulin needs. We are reporting a... (Review)
Review
OBJECTIVE
Patients with type 1 diabetes mellitus (T1DM) are insulin dependent. Infection increases insulin resistance and subsequently increases insulin needs. We are reporting a case of a patient with T1DM and severe infection who has reduced insulin needs after starting micafungin therapy.
PARTICIPANT
A 29-year-old Hispanic woman with known history of long-standing, uncontrolled T1DM presented for evaluation of worsening dysphagia and dyspnea. She was found to have cervical necrotizing fasciitis extending into the mediastinum and required several debridement surgeries along with broad-spectrum antibiotics and antifungal therapy. She had uncontrolled diabetes with a glycosylated hemoglobin of 13.4% (18.8 mM) on admission. Her insulin requirements progressively increased as a result of worsening infection, continuous tube feeds, and multiple debridement surgeries. She was started on micafungin, a potent 1,3-β-D glucan synthase inhibitor, to broaden antimicrobial coverage when her insulin requirement decreased to zero for >48 hours. Right after discontinuation of micafungin and her switch to a different antifungal, insulin requirements increased back to her baseline needs.
RESULTS
This is a report of decreased insulin requirements in a patient with T1DM correlating with micafungin administration. The mechanism of micafungin-induced hypoglycemia is not yet established. Oral administration of linear 1,3-β-D glucan has been documented to decrease blood glucose levels significantly by inhibition of expression of sodium-glucose transporter 1 (SGLT1) in intestinal mucosa.
CONCLUSION
We hypothesize that micafungin may inhibit SGLT-1 function and decrease insulin requirements in patient with T1DM.
Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Blood Glucose; Debridement; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Substitution; Drug Therapy, Combination; Fasciitis, Necrotizing; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Intestinal Mucosa; Micafungin; Sodium-Glucose Transporter 1
PubMed: 30398618
DOI: 10.1210/jc.2018-02017 -
Clinical Pharmacokinetics Mar 2018Micafungin 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... (Review)
Review
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
PubMed: 28791666
DOI: 10.1007/s40262-017-0578-5 -
The Pediatric Infectious Disease Journal Nov 2014Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants. (Comparative Study)
Comparative Study Review
BACKGROUND
Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants.
METHODS
Safety and efficacy outcomes of micafungin were compared between prematurely and non-prematurely born infants <2 years of age. Data were obtained from all completed phase I-III clinical trials with micafungin that had enrolled infants (<2 years of age) that were listed in the Astellas Clinical Study Database. Demographics, adverse events, hepatic function tests and treatment success data were extracted and validated by the Astellas biostatistical group for all micafungin-treated patients, <2 years of age, using the unique patient identifier.
RESULTS
One-hundred and sixteen patients included in 9 clinical trials, 48% premature [birth weight (BW) <2500 g and/or gestational age <37 weeks], 52% non-premature, received ≥ 1 dose of micafungin. Among premature patients, 14.5% were low BW (1500-2499 g), 36.4% very low BW (1000-1499 g) and 49.1% extremely low BW (<1000 g). Ninety patients (78%) completed the studies; 13 [11% (4 premature)] died. Significantly more non-premature than premature patients discontinued treatment (P = 0.003). Treatment-related adverse events were recorded in 23% of patients with no difference between groups. More extremely low BW (n = 4, 15%) and very low BW (n = 8, 40%) infants experienced treatment-related adverse events than low BW (n = 0) and there was no relation to micafungin dose or duration. For a subgroup of 30 patients with invasive candidiasis, treatment success was achieved in 73% in both premature and non-premature groups. Prophylaxis was successful in 4/5 non-premature hematopoietic stem cell transplant patients.
CONCLUSION
Micafungin has a safe profile in premature and non-premature infants with substantial efficacy.
Topics: Antifungal Agents; Clinical Trials as Topic; Echinocandins; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Micafungin; Mycoses; Term Birth
PubMed: 24892849
DOI: 10.1097/INF.0000000000000434 -
Expert Opinion on Pharmacotherapy Dec 2022Invasive candidiasis remains a leading cause of morbidity and mortality in various categories of patients at risk. (Review)
Review
INTRODUCTION
Invasive candidiasis remains a leading cause of morbidity and mortality in various categories of patients at risk.
AREAS COVERED
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.
EXPERT OPINION
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 meningoencephalitis. The recent worrisome worldwide diffusion of , more frequently resistant to polyenes than to echinocandins and showing high rates of resistance to azoles, could render micafungin even more crucial for guaranteeing an efficacious antifungal treatment for invasive candidiasis in pediatric patients younger than 4 months old.
Topics: Humans; Child; Infant; Micafungin; Lipopeptides; Candidiasis, Invasive; Echinocandins; Antifungal Agents
PubMed: 36373395
DOI: 10.1080/14656566.2022.2147824 -
Expert Review of Anti-infective Therapy Apr 2005Invasive fungal infections cause considerable morbidity and mortality in nosocomial settings and amongst immunocompromised hosts. Invasive candidiasis and aspergillosis... (Review)
Review
Invasive fungal infections cause considerable morbidity and mortality in nosocomial settings and amongst immunocompromised hosts. Invasive candidiasis and aspergillosis remain the most common invasive fungal infections, with Candida spp. constituting the fourth most common bloodstream infection in the USA. Currently available antifungal therapies include the polyene, antimetabolite, allylamine, azole and echinocandin drug classes. Micafungin, approved in March 2005 by the Food and Drug Administration for use in the USA, has shown safety and efficacy for the treatment of candidiasis and aspergillosis in clinical trials in Japan, Europe and South Africa. Micafungin holds promise as a first-line treatment option for candidiasis, as well as prophylaxis against invasive fungal infections during periods of neutropenia in high-risk patients.
Topics: Animals; Antifungal Agents; Clinical Trials as Topic; Echinocandins; Humans; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Peptides, Cyclic; Safety
PubMed: 15918776
DOI: 10.1586/14787210.3.2.183 -
Drugs of Today (Barcelona, Spain : 1998) Jun 2009Micafungin is one of three currently FDA-approved echinocandins. It has potent in vitro activity against Candida species including non-albicans Candida and... (Review)
Review
Micafungin is one of three currently FDA-approved echinocandins. It has potent in vitro activity against Candida species including non-albicans Candida and azole-resistant Candida species and has also demonstrated clinical efficacy against deep-seated Candida infections. Additional in vitro data and preliminary clinical efficacy studies suggest that it also has utility for the treatment of infections caused by Aspergillus species. However, its approved indications remain for the treatment of both invasive and esophageal candidiasis and for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. is generally well tolerated with few significant adverse effects.
Topics: Animals; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug Interactions; Echinocandins; Humans; Lipopeptides; Micafungin
PubMed: 19856528
DOI: 10.1358/dot.2009.45.6.1378277 -
Drugs Nov 2012Intravenous micafungin (Mycamine®; Fungard®), an echinocandin, is approved in the EU for the treatment of adult (aged ≥ 16 years) and paediatric patients with... (Review)
Review
Intravenous micafungin (Mycamine®; Fungard®), an echinocandin, is approved in the EU for the treatment of adult (aged ≥ 16 years) and paediatric patients with invasive candidiasis and for the treatment of adult patients with oesophageal candidiasis. It is also approved in the EU as prophylactic treatment to prevent Candida infections in adult and paediatric patients undergoing haematopoietic stem cell transplant (HSCT) or patients who are expected to have neutropenia for ≥ 10 days. This article reviews the therapeutic use of micafungin for the treatment and prophylaxis of Candida infections in adult and paediatric patients, focusing on approved indications in Europe, and briefly discusses the pharmacology of the drug. Micafungin shows very good in vitro activity against clinically relevant isolates of Candida spp., with a low propensity to be associated with the emergence of resistant isolates. The drug has a convenient once-daily dosage regimen and is associated with relatively few drug-drug interactions. In large, multinational trials in adult and/or paediatric patients with invasive candidiasis, micafungin was noninferior to intravenous caspofungin or liposomal amphotericin B. In similarly designed trials in adult patients with oesophageal candidiasis, treatment with micafungin was noninferior to that with intravenous fluconazole or caspofungin. As prophylactic treatment in adult and paediatric patients who had undergone HSCT, micafungin was superior to fluconazole therapy and noninferior to oral itraconazole in large, multicentre trials. Micafungin was generally well tolerated by participants in these clinical trials, given the severe morbidity of the underlying conditions of patients, with a similar tolerability profile to caspofungin and, in general, to fluconazole. It was better tolerated than liposomal amphotericin B or oral itraconazole. Thus, micafungin is a valuable first-line or alternative option to other antifungal agents for the management of candidaemia and invasive candidiasis in adult and paediatric patients, including neonates, and as prophylaxis against fungal infections in patients undergoing HSCT.
Topics: Antifungal Agents; Candida; Candidiasis; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Micafungin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23083111
DOI: 10.2165/11209970-000000000-00000 -
Critical Reviews in Analytical Chemistry 2021Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases... (Review)
Review
Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases of invasive fungal infections. The use of this drug is widely appreciated in the medical field due to be the most active echinocandin available for invasive fungal infections. In order to provide important parameters related to the chemical, physical, biological and therapeutic characteristics, this review article gathers important research results that demonstrate the biological potential of this drug, as well as to present analytical methods that can be used to determine the antifungal potential and a monitoring of administered dosages. Important studies about the methods most commonly used in biological activity evaluation and determination/quantification by analytical methods are provided in this review article. With the data provided, the scientific community will have the possibility to choose the analytical methods and biological that can be employed in clinical and scientific research to provide greater safety and reliability of the results to be found.
Topics: Antifungal Agents; Aspergillus fumigatus; Candida; Candidiasis; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Echinocandins; Electrophoresis, Capillary; Humans; Micafungin; Solubility; Tandem Mass Spectrometry; Treatment Outcome
PubMed: 32064916
DOI: 10.1080/10408347.2020.1726726