micafungin and Infant--Premature--Diseases

Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants.. 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.. 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.. 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

Micafungin is an echinocandin approved by the European Medicines Evaluation Agency for the treatment of invasive candidiasis in children, including premature infants born before 29 weeks of pregnancy, and as prophylaxis in children undergoing hematopoietic stem-cell transplantation or patients at risk of prolonged neutropenia. This drug has good activity in several Candida spp., including those resistant to fluconazole. Although micafungin is active against Aspergillus spp., it has been used mainly in combination therapy for invasive aspergillosis. There is ample information on the use of micafungin in children, including neonates, and this drug is the only echinocandin approved for use in infants aged less than 3 months. The efficacy, pharmacokinetics and safety of micafungin have been evaluated in phase II and III clinical trials in children, in which its efficacy and safety were demonstrated in comparison with liposomal amphotericin B and fluconazole. The pharmacokinetic profile of micafungin in children allows once daily intravenous administration, with greater clearance than in adults, and consequently pediatric doses are relatively higher. The most appropriate dose in children weighing less than 40 kg is 2 mg/kg/day in the treatment of invasive candidiasis and 1 mg/kg/day as prophylaxis in children undergoing hematopoietic stem-cell transplantation. Doses in neonates should be higher. In premature infants, the most appropriate doses to achieve levels in the brain parenchyma are 7 mg/kg/day and 10 mg/kg/day in those weighing more and less than 1,000 g, respectively. Micafungin has few drug-drug interactions and an acceptable safety profile. Withdrawal of this drug due to adverse effects is rare, although transaminase monitoring is recommended during treatment, as well as evaluation of the risk-benefit balance in patients with liver disease or concomitant administration of hepatotoxic drugs.

Topics: Adolescent; Adult; Age Factors; Animals; Antifungal Agents; Blood-Brain Barrier; Body Weight; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Approval; Drug Evaluation, Preclinical; Echinocandins; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Meta-Analysis as Topic; Micafungin; Multicenter Studies as Topic; Mycoses; Rabbits; Randomized Controlled Trials as Topic

The burden of neonatal invasive Candida infection (ICI) has been increasing recently and identification of effective preventative and treatment strategies is a priority. In this view, the echinocandin class of antifungal agents has emerged as a suitable and promising option for treatment. These agents have overall characteristics that suitably meet the needs of neonatal patients, such as coverage against biofilms and against fluconazole-resistant strains of Candida spp, which is an issue in an epoch of increasing prophylactic use of fluconazole in the nursery. Micafungin is the only echinocandin authorized for neonatal use by the EMA, based on efficacy and PK data from neonatal populations. Although the kinetics and appropriate dosing of this agent in premature and term infants have been described in the recent years, through either neonatal studies or extrapolation form adult data, further studies are needed to better address this area. These studies should be properly designed for neonatal populations, and must better address long-term safety and the clinical outcomes related to echinocandin use in neonates.

Topics: Adult; Antifungal Agents; Candidiasis; Dose-Response Relationship, Drug; Echinocandins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Micafungin

In neonatal intensive care units, deep fungal disease due to Candida spp. are an important clinical problem, partly due to the increasing prevalence of Candida disease and also to the high associated and constant morbimortality; both factors are independently maintained though there has been a significant improvement in the management of neonatal patients.. To define the therapeutic use of micafungin for the treatment of neonatal invasive candidiasis.. We use a review of biomedic data bases namely Medline and EMBASE.. Micafungin is the latest introduced echinocandin. It has a wide spectrum of activity and covers Candida albicans and non-albicans Candida species. It has scarce drugs interactions and is devoid of toxicity, being an attractive approach for the treatment of invasive candidiasis (without meningitis, endocarditis and endophthalmitis). Althought the European Medicines Agency approved in 2008 the use of Micafungin for the treatment of invasive candidiasis in children, the available clinical experience is limited and currently more clinical studies are warranted to define its efficacy and safety in neonates.

Topics: Adolescent; Adult; Age Factors; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Clinical Trials as Topic; Echinocandins; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Male; Meta-Analysis as Topic; Micafungin; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies

: Candidal fungal infection rates in neonates are increasing and are a significant cause of mortality, especially in low birth weight infants. Micafungin is an echinocandin that works by inhibiting 1,3-beta-D-glucan synthase, an enzyme responsible for fungal cell wall synthesis. The objective of this study was to determine the safety and pharmacokinetics of micafungin in premature infants.. : This was a phase I, single-dose, multicenter, open-label, sequential-dose trial of intravenous micafungin investigating 3 doses (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg) in 18 premature infants weighing >1000 g (n = 6 in each dosage group). A further 5 infants (500-1000 g) were enrolled in the 0.75 mg/kg dosage group only.. : The mean +/- standard deviation gestational age in the >1000 g dosage group was 26.4 +/- 2.4 weeks and, on entry, patients had one or more of a variety of underlying conditions, including sepsis, pneumonia and other infections caused by Candida or other species. Micafungin pharmacokinetics in preterm infants appears linear. However, premature infants >1000 g on average displayed a shorter half-life (8 hours) and a more rapid rate of clearance (approximately 39 mL/h per kg) compared with published data in older children and adults. All doses of micafungin were well tolerated and no serious drug-related adverse events were observed.. : Single doses of micafungin, ranging up to 3.0 mg/kg, appear well tolerated in premature infants weighing >1000 g. The drug's elimination half-life and total plasma clearance in preterm infants appear dissimilar to published values for these parameters in older children and adults. The reason(s) for this apparent difference remain to be investigated.

Topics: Antifungal Agents; Candidiasis; Echinocandins; Female; Half-Life; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Intravenous; Lipopeptides; Lipoproteins; Male; Metabolic Clearance Rate; Micafungin; Peptides, Cyclic; Pneumonia; Sepsis

We conducted a comparative clinical study to evaluate the prophylactic effects of micafungin (MCFG) and fluconazole (FLCZ) on the incidence of fungal infections in extremely low-birthweight infants who were born at a gestational age of less than 26 weeks and weighed less than 1000 g.. With a combination of enteral administration of miconazole (6 mg/kg/day), FLCZ and MCFG were administered intravenously at a dose of 5 mg/kg/day and 3 mg/kg/day, respectively. The prophylaxis was classified as a failure when fungal infections were identified within the first 21 days after birth.. The prophylaxis was successful in seven of 18 cases (39%) in the FLCZ group and 15 of 21 cases (71%) in the MCFG group, indicating that the success rate was significantly higher in the latter group.. MCFG was superior to FLCZ as prophylaxis against fungal infections in extremely low-birthweight infants.

Topics: Antifungal Agents; Echinocandins; Female; Fluconazole; Historically Controlled Study; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Male; Micafungin; Mycoses

We report the case of a 31-week gestational age neonate with Candida albicans sepsis and a hepatic abscess. Diagnosis relied on clinical and radiological signs of sepsis, liver function impairment and culture isolation of Candida spp. from sterile sites. Liver ultrasound documented the presence of a multiloculated abscess. Treatment with micafungin (3 mg/kg/day) resulted in normalization of liver function and inflammatory laboratory values and improvement of clinical condition. After 30 days of treatment, the liver abscess resolved and at the 8-month follow up the infant is doing well. Prompt diagnosis and antifungal treatment avoided surgical drainage and liver surgery in this high-risk neonate.

Topics: Antifungal Agents; Candidiasis; Echinocandins; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Liver; Liver Abscess; Male; Micafungin; Treatment Outcome; Ultrasonography

Micafungin is an echinocandin-class antifungal agent licensed for treatment of invasive disease in adults. The optimal dosing regimens have not been established for infants. We describe a premature infant who developed hepatitis and cholestasis during micafungin therapy initiated for protracted candidemia. Practitioners should be aware of this potential adverse effect if using micafungin in young patients.

Topics: AIDS-Related Opportunistic Infections; Alanine Transaminase; Amphotericin B; Antifungal Agents; Aspartate Aminotransferases; Candidiasis; Chemical and Drug Induced Liver Injury; Cholestasis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Echinocandins; Female; Fungemia; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Lipopeptides; Liver Function Tests; Micafungin

Although clinical experience in neonates with candidiasis exists for amphotericin B and fluconazole, these standard treatments are often hindered by drug-associated toxicity or development of resistant strains. The aim of the present study was therefore to investigate the efficacy and tolerability of a new antifungal agent, micafungin (MCFG), for treating Candida infections in premature infants.. This was a retrospective cohort study. Premature infants diagnosed with Candida infections from October 2003 to July 2004 were brought to the neonatal intensive care unit at the Center of Perinatal Medicine, Nara Medical University Hospital. Four newborns were given 0.5-1.0 mg/kg per day micafungin.. Four premature infants (mean +/- SD gestational age, 24.1 +/- 0.9 weeks; mean +/- SD birthweight, 579.3 +/- 80.5 g) experienced complications from Candida infection; two cases of the fungal infection were caused by Candida glabrata and two cases were caused by Candida albicans. MCFG was administered at 0.5 or 1.0 mg/kg per day (mean dosage days, 9.8 +/- 3.1 days) and it decreased beta-D-glucan levels while improving clinical symptoms in all cases. Additionally, there were no apparent side-effects.. MCFG is both effective and tolerable for use in premature infants suffering from Candida infections.

Topics: Antifungal Agents; beta-Glucans; Candidiasis; Echinocandins; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Male; Micafungin; Retrospective Studies; Treatment Outcome

Preterm neonates with candidemia frequently have persistently positive blood cultures, despite the use of conventional antifungal therapy. Our institutional treatment protocol for invasive candidiasis incorporates lipid complex amphotericin B as initial therapy with the sequential addition of fluconazole and high-dose micafungin (10 mg kg(-1)) every 48 to 72 h, if cultures from a sterile site remain positive. Our study objectives were to compare the clinical profiles and outcomes of preterm neonates with candidemia that responded to or were refractory to conventional antifungals. We further evaluate the clinical efficacy of high-dose micafungin pharmacotherapy of refractory candidemia.. A chart review was performed on preterm infants (n=29) with invasive candidiasis and demographic, microbiologic and outcome data abstracted. Proportions and continuous variables were compared between the groups using Fisher's exact two-tailed test and t-test.. The refractory (n=19) candidemia and early responder (n=10) groups had comparable mean (+/-s.d.) gestation, 27(+/-3.1) vs 27.8 (+/-2.7) weeks. The refractory group was administered antibiotics for a longer duration, 14.5 (+/-10.3) vs 7.1 (+/-5) days, had a preponderance of non-albicans infections, 11 (57.9%) vs 1 (10%) and were on enteral feeds > 20 ml kg(-1) day(-1) significantly less often (21 vs 70%). Mortality was significantly higher (53 vs 20%) and fungal clearance rates lower (63.1 vs 90%), with a longer duration to clearance in the group with refractory candidemia. Mean aspartate aminotransferase (AST) showed a statistically significant increase following micafungin treatment, although clinical significance remains unclear.. Candidemia refractory to conventional antifungals is associated with prolonged antibiotic use, lack of enteral nutritive feeds and non-albicans infection. Despite high-dose micafungin pharmacotherapy in combination with conventional antifungals, infants with refractory candidemia had high mortality and poor fungal clearance.

Topics: Anti-Bacterial Agents; Antifungal Agents; Aspartate Aminotransferases; Candidiasis; Cohort Studies; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Drug Therapy, Combination; Echinocandins; Enteral Nutrition; Female; Fungemia; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Lipopeptides; Long-Term Care; Male; Micafungin; Retrospective Studies; Risk Factors; Survival Rate; Treatment Outcome

Treatment options for primary cutaneous aspergillosis in neonates are limited by the lack of pharmacokinetic and safety data of newer antifungal agents that are effective against Aspergillus spp. We report the successful treatment of cutaneous aspergillosis in an extremely low-birth-weight preterm infant with liposomal amphotericin B, voriconazole and micafungin, and provide pharmacokinetic profiles for voriconazole and micafungin.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Dermatomycoses; Echinocandins; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lipopeptides; Lipoproteins; Micafungin; Peptides, Cyclic; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Long-term inserted and surgically implanted catheters can be colonised by Candida spp. Candida biofilms in vitro are often resistant to antifungal agents. The aim of this study was to investigate the in vitro activity of micafungin (MFG) against six Candida spp. biofilms on polystyrene (PS) and central venous catheter (CVC) sections. Safranin staining and differential interference contrast microscopy were used to demonstrate biofilm production. MFG activity was determined by the reduction in metabolic activity (%RMA) by tetrazolium reduction assay on both substrates. In vitro, Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida dubliniensis and Candida kefyr produced mature biofilms on PS and CVC sections. MFG was active against C. kefyr (0.5 microg/mL) and C. glabrata (<0.5 microg/mL) on PS. However, MFG displayed resistance (>16 microg/mL) against C. albicans, C. dubliniensis,C. tropicalis and C. parapsilosis. On CVC disks, MFG was active against C. glabrata (1 microg/mL) as well as C. parapsilosis and C. albicans (<0.5 microg/mL). MFG was resistant (>16 microg/mL) against C. dubliniensis, C. tropicalis and C. kefyr. MFG was active in vitro against all six Candida spp. on both substrates. However, MFG could not reduce the metabolic activity completely even at the highest concentration.

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Biofilms; Candida; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Child; Echinocandins; Humans; Infant, Newborn; Infant, Premature, Diseases; Lipopeptides; Lipoproteins; Micafungin; Microbial Sensitivity Tests; Microscopy, Interference; Peptides, Cyclic; Phenazines; Polystyrenes; Staining and Labeling; Tetrazolium Salts