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European Journal of Medical Research Apr 2011Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in... (Review)
Review
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
PubMed: 21486730
DOI: 10.1186/2047-783x-16-4-159 -
Current Medical Mycology Mar 2022Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in species constitutes a serious concern. This...
BACKGROUND AND PURPOSE
Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in species constitutes a serious concern. This study aimed to evaluate the efficacy of nystatin, and micafungin with chlorhexidine against fluconazole-resistant and fluconazole-sensitive () isolates.
MATERIALS AND METHODS
In this experimental-laboratory study, a total of 20 fluconazole-resistant (n=10) and fluconazole-susceptible (n=10) strains were obtained from the reference culture collection of the Invasive Fungi Research Center in Mazandaran University of Medical Sciences, Sari, Iran. combination of nystatin and micafungin with chlorhexidine was performed using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute guideline.
RESULTS
Micafungin had the highest antifungal activity against susceptible and resistant strains, with a Geometric mean of (GM) =0.008µg/ml and GM=0.008µg/ml, followed by nystatin with GM=0.06µg/ml and GM=0.042µg/ml and chlorhexidine with GM=0.25µg/ml and GM=0.165µg/ml against resistant and sensitive strains, respectively. The interaction of micafungin and nystatin with chlorhexidine showed a synergistic interaction against most strains. In addition, no antagonistic interaction was observed between micafungin, nystatin, and chlorhexidine against strains.
CONCLUSION
The synergistic interaction of micafungin with chlorhexidine against azole-resistant suggests an alternative approach to overcome antifungal drug resistance. However, further studies are needed for evaluation.
PubMed: 36340437
DOI: 10.18502/cmm.8.1.9208 -
Expert Opinion on Drug Safety Mar 2011Invasive Candida infections are a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Micafungin is a promising therapeutic option for... (Review)
Review
INTRODUCTION
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.
AREAS COVERED
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'.
EXPERT OPINION
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
PubMed: 21226655
DOI: 10.1517/14740338.2011.545345 -
Medical Mycology Sep 2022The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are... (Observational Study)
Observational Study
Distribution, trends, and antifungal susceptibility of Candida species causing candidemia in Japan, 2010-2019: A retrospective observational study based on national surveillance data.
The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010-2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.
Topics: Amphotericin B; Antifungal Agents; Azoles; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Drug Resistance, Fungal; Fluconazole; Humans; Japan; Micafungin; Microbial Sensitivity Tests; Voriconazole
PubMed: 36095139
DOI: 10.1093/mmy/myac071 -
Indian Journal of Medical Microbiology 2018The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting.... (Review)
Review
The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.
Topics: Anidulafungin; Antifungal Agents; Biofilms; Candida; Candidiasis; Caspofungin; Critical Illness; Cross Infection; Drug Resistance, Fungal; Echinocandins; Humans; Intensive Care Units; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Tertiary Healthcare
PubMed: 29735833
DOI: 10.4103/ijmm.IJMM_17_400 -
Expert Opinion on Pharmacotherapy May 2015Invasive candidiasis is responsible for ∼ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over... (Review)
Review
INTRODUCTION
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.
AREAS COVERED
We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis.
EXPERT OPINION
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
PubMed: 25842986
DOI: 10.1517/14656566.2015.1031108 -
European Journal of Medical Research Apr 2011Invasive 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... (Review)
Review
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
PubMed: 21486732
DOI: 10.1186/2047-783x-16-4-180 -
Antimicrobial Agents and Chemotherapy Mar 2021Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study...
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
PubMed: 33558294
DOI: 10.1128/AAC.02494-20 -
British Journal of Clinical Pharmacology Sep 2018The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis.
METHODS
Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg ; maintenance dose 12 mg kg day or 20 mg kg day , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg day ; maintenance dose 10 mg kg day ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge.
RESULTS
Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h kg ) and volume of distribution (l kg ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported.
CONCLUSION
Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.
Topics: Age Factors; Animals; Antifungal Agents; Area Under Curve; Candidiasis; Female; Fluconazole; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Micafungin; Mice; Prospective Studies
PubMed: 29744900
DOI: 10.1111/bcp.13628 -
Journal of Infection in Developing... Jun 2021An echinocandin, such as micafungin, is recommended as first-line treatment for invasive Candida infections in immunocompromised patients. This multicenter,... (Observational Study)
Observational Study
INTRODUCTION
An echinocandin, such as micafungin, is recommended as first-line treatment for invasive Candida infections in immunocompromised patients. This multicenter, observational, prospective, non- interventional study evaluated the real-world use of micafungin in clinical practice in Slovenia and Romania, as this remains unexplored.
METHODOLOGY
The primary endpoint was evaluation of micafungin use, including rationale for prescription, treatment duration, and daily dose. Secondary endpoints included recordings of patient baseline characteristics and evaluations of efficacy and safety. Across 11 centers in two countries, 118 patients (18 children [< 16 years] and 100 adults [≥ 16 years]) received micafungin for the first time according to their clinic's standard practice.
RESULTS
Micafungin was prescribed for treatment in 57.6% of patients and for prophylaxis in 40.7% of patients. The median (range) treatment duration was 9.0 (0 - 54) days and 13.0 (2 - 6)] days, respectively. The median dose of micafungin was higher than recommended for children receiving prophylaxis or treatment for invasive candidiasis and for adults receiving prophylaxis. Fever was the most commonly observed clinical sign at baseline (16 children [88.9%] and 31 adults [31%]) and hematologic malignancy was the most frequent primary diagnosis at admission (11 children [61.1%] and 40 adults [40%]). Candida species were the most commonly identified causal agents of invasive fungal infections (2 children [11.1%] and 48 adults [48%]).
CONCLUSIONS
The efficacy and safety profiles of micafungin use in Slovenia and Romania based on clinician's own experiences in local clinical practice were consistent with those reported in other real-world studies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Candidiasis; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Infant, Newborn; Male; Micafungin; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Romania; Slovenia; Young Adult
PubMed: 34242200
DOI: 10.3855/jidc.12755