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Antimicrobial Agents and Chemotherapy Oct 2012Voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis. Isolates with elevated voriconazole MICs are increasingly being seen, and the...
Voriconazole is a first-line agent for the treatment of invasive pulmonary aspergillosis. Isolates with elevated voriconazole MICs are increasingly being seen, and the optimal treatment regimen is not defined. We investigated whether the combination of voriconazole with anidulafungin may be beneficial for the treatment of A. fumigatus strains with elevated voriconazole MICs. We used an in vitro model of the human alveolus to define the exposure-response relationships for a wild-type strain (voriconazole MIC, 0.5 mg/liter) and strains with defined molecular mechanisms of triazole resistance (MICs, 4 to 16 mg/liter). All strains had anidulafungin minimum effective concentrations (MECs) of 0.0078 mg/liter. Exposure-response relationships were estimated using galactomannan as a biomarker. Concentrations of voriconazole and anidulafungin were measured using high-performance liquid chromatography (HPLC). The interaction of voriconazole and anidulafungin was described using the Greco model. Fungal growth was progressively inhibited with higher drug exposures of voriconazole. Strains with elevated voriconazole MICs required proportionally greater voriconazole exposures to achieve a comparable antifungal effect. Galactomannan concentrations were only marginally reduced by anidulafungin monotherapy. An additive effect between voriconazole and anidulafungin was apparent. In conclusion, the addition of anidulafungin does not markedly alter the exposure-response relationship of voriconazole. A rise in serum galactomannan during combination therapy with voriconazole and anidulafungin should be interpreted as treatment failure and not attributed to a paradoxical reaction related to echinocandin treatment.
Topics: Anidulafungin; Antifungal Agents; Aspergillus fumigatus; Cell Line; Chromatography, High Pressure Liquid; Drug Interactions; Echinocandins; Humans; Invasive Pulmonary Aspergillosis; Microbial Sensitivity Tests; Models, Theoretical; Pulmonary Alveoli; Pyrimidines; Triazoles; Voriconazole
PubMed: 22825124
DOI: 10.1128/AAC.01111-12 -
Peritoneal Dialysis International :... 2014
Comparative Study
Topics: Anidulafungin; Candidiasis; Dialysis Solutions; Drug Stability; Echinocandins; Humans; Mycoses; Peritoneal Dialysis; Peritonitis; Sampling Studies
PubMed: 25520485
DOI: 10.3747/pdi.2012.00326 -
Antimicrobial Agents and Chemotherapy Aug 2021Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined and . MICs for anidulafungin,...
Efficacy of Voriconazole, Isavuconazole, Fluconazole, and Anidulafungin in the Treatment of Emerging Candida auris Using an Immunocompromised Murine Model of Disseminated Candidiasis.
Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined and . MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 μg/ml, respectively. Significant efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group ( values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant activity.
Topics: Anidulafungin; Animals; Antifungal Agents; Candida; Candidiasis; Disease Models, Animal; Fluconazole; Mice; Microbial Sensitivity Tests; Nitriles; Pyridines; Triazoles; Voriconazole
PubMed: 34228541
DOI: 10.1128/AAC.00549-21 -
Enfermedades Infecciosas Y... Dec 2008Despite recent advances in antifungal therapy, the incidence of invasive Candida infections and resulting mortality have remained unchanged in the last few years. In... (Review)
Review
Despite recent advances in antifungal therapy, the incidence of invasive Candida infections and resulting mortality have remained unchanged in the last few years. In surveillance studies published to date, the estimated incidence of candidemia differs depending on the geographic area and is significantly higher in North America than in Europe. The main predisposing conditions for candidemia are neutropenia, cellular immunity deficit, and alteration of normal microbial flora. Some independent risk factors have been identified, such as previous colonization, antibiotic therapy, central venous catheters, neutropenia, and renal dysfunction. In the last two decades, the proportion of infections due to non-albicans Candida has markedly increased. Although fluconazole use has been considered one of the main causes for the epidemiologic change in invasive candidiasis, especially in the increase of species less sensitive to this agent, this association remains unproven. These recent epidemiological changes are highly important when selecting treatment for candidemia. The echinocandins, which include anidulafungin, represent a step forward in the treatment of these infections. The clinical efficacy, tolerability and safety of anidulafungin have been demonstrated in controlled clinical trials in candidemia and invasive candidiasis. Current recommendations include this antifungal agent in the initial empirical therapy of certain patients, especially in those with a critical clinical situation, previous azole exposure, or the possibility of developing adverse events or drug interactions.
Topics: Adult; Aged; Anidulafungin; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Disease Susceptibility; Double-Blind Method; Drug Resistance, Fungal; Echinocandins; Fluconazole; Fungemia; Gastrointestinal Diseases; Global Health; Humans; Middle Aged; Multicenter Studies as Topic; Neutropenia; Risk Factors; Species Specificity
PubMed: 19572431
DOI: 10.1016/s0213-005x(08)76589-3 -
Clinical Infectious Diseases : An... Dec 2015The etiology of cardiomyopathies are classified into 4 main groupings (dilated, hypertrophic, restrictive, and idiopathic) and can be mechanistically caused by... (Review)
Review
The etiology of cardiomyopathies are classified into 4 main groupings (dilated, hypertrophic, restrictive, and idiopathic) and can be mechanistically caused by myocarditis, conduction abnormalities, focal direct injury, or nutritional deficiency. Based on our review of this topic, evidence suggests that echinocandin-related cardiac dysfunction is a mitochondrial drug-induced disease caused by focal direct myocyte injury. With caspofungin or anidulafungin administration into the heart via central line, exposure is likely extreme enough to induce the acute toxicity. Chronic or low-dose exposure may lead to hypertrophic cardiomyopathy; however, only acute exposures have been explored to date.
Topics: Anidulafungin; Animals; Antifungal Agents; Cardiac Output; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiotoxicity; Caspofungin; Echinocandins; Echocardiography; Humans; Lipopeptides; Mitochondria, Heart
PubMed: 26567285
DOI: 10.1093/cid/civ739 -
BMC Infectious Diseases Sep 2016In critically ill patients the incidence of invasive fungal infections caused by Candida spp. has increased remarkably. Echinocandins are recommended as initial... (Clinical Trial)
Clinical Trial
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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: APACHE; Anidulafungin; Antifungal Agents; 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
PubMed: 27634140
DOI: 10.1186/s12879-016-1825-3 -
Medical Mycology Jun 2017Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus...
Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus posaconazole have shown efficacy against a murine systemic infection by three strains of Aspergillus fumigatus. The combination increased mice survival and reduced burden in the kidneys over the corresponding monotherapies and voriconazole. Clearance of kidneys was observed in 62% to 100% of animals (strain dependant). We observed good in vitro- in vivo correlation when a cutoff < 1 was indicative of synergy. Our results showed that the combination could be a therapeutical option, especially against infections refractory to the first line therapy.
Topics: Anidulafungin; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Echinocandins; Kidney; Male; Mice; Survival Analysis; Triazoles
PubMed: 27760829
DOI: 10.1093/mmy/myw110 -
Pharmacotherapy Mar 2007The changing pattern in fungal infections has driven the need to expand the targets of antifungal activity. The echinocandins are the newest addition to the arsenal... (Review)
Review
The changing pattern in fungal infections has driven the need to expand the targets of antifungal activity. The echinocandins are the newest addition to the arsenal against fungal infections. Three echinocandins have been approved by the United States Food and Drug Administration: caspofungin, micafungin, and anidulafungin. These agents have a broad spectrum of activity and are similar to each other with respect to in vitro activity against Candida sp, with micafungin and anidulafungin having similar minimum inhibitory concentrations (MICs) that are generally lower than the MIC of capsofungin. The MICs of the echinocandins are highest against Candida parapsilosis; however, whether this will affect clinical outcomes is unknown. Several case reports have identified clinical failure due to elevated MICs with caspofungin or micafungin against Candida albicans, Candida krusei, and C. parapsilosis. Resistance to the echinocandin class was present in some but not all of the isolates. Empiric therapy with one of the echinocandins for candidemia or invasive candidiasis in patients with neutropenia and those without neutropenia appears to be appropriate when one factors in mortality rate, the increasing frequency of non-albicans Candida infections, and the broad spectrum, safety, and fungicidal effect of the echinocandins. After speciation of the organism, continued therapy with an echinocandin can and should be reevaluated. The echinocandins demonstrate similar in vitro and in vivo activity against Aspergillus sp, but only caspofungin is approved for treatment in patients who are intolerant of or refractory to other therapies. Voriconazole and amphotericin B have demonstrated synergy with the echinocandins. The clinical response to combination therapy has been variable; however, the mortality rate appears to be lower with combination therapy than monotherapy. Large controlled trials are needed to determine the role of combination therapy for invasive aspergillosis. Micafungin and anidulafungin generally have a lower frequency of adverse reactions compared with caspofungin. Phlebitis (3.5-25% of patients) and elevated liver enzyme levels (1-15%) occur more often with caspofungin compared with micafungin and anidulafungin (< 8%). Overall, the three echinocandins are relatively safe and effective agents for the treatment of Candida infections.
Topics: Anidulafungin; Antifungal Agents; Aspergillus; Candida albicans; Caspofungin; Cryptococcus; Echinocandins; Fungal Proteins; Humans; Lipopeptides; Lipoproteins; Micafungin; Microbial Sensitivity Tests; Mycoses; Peptides, Cyclic
PubMed: 17316149
DOI: 10.1592/phco.27.3.369 -
Journal de Mycologie Medicale Sep 2021The aim of the present study was to evaluate the in vitro susceptibility of anidulafungin, caspofungin, fluconazole and conventional amphotericin B against biofilms and...
In vitro activity of anidulafungin, caspofungin, fluconazole and amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies.
OBJECTIVE
The aim of the present study was to evaluate the in vitro susceptibility of anidulafungin, caspofungin, fluconazole and conventional amphotericin B against biofilms and planktonic forms of Candida species isolated from blood culture in patients with hematological malignancies.
MATERIALS AND METHODS
Antifungal susceptibility for planktonic forms and biofilms of Candida was determined by broth microdilution method as described by Clinical and Laboratory Standards Institute M27 methodology and metabolic XTT-based [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay, respectively.
RESULTS
A total of 75 Candida isolates were evaluated between 2006-2018 yy at the National Research Center for Hematology, Russia, Moscow. Biofilm production was detected in 34 (45.3%) Candida species. Antifungal susceptibility was tested for 27 common species of Candida forming biofilms (8 C.krusei, 7 C.tropicalis, 7 C.albicans, 5 C.parapsilosis). MICs below the susceptibility breakpoints were found for 100% of planktonic forms of Candida species for anidulafungin, 85.2% for caspofungin, and 66.7% for fluconazole. Amphotericin B MIC for Candida species were less than or equal to 1 μg/ml. Candida biofilms were susceptible in vitro for both tested echinocandins, but MIC of anidulafungin were lower compared to caspofungin. The highest MIC against Candida biofilms was found for fluconazole (>1,024 μg/ml for all tested isolates) and for conventional amphotericin B (range 4-16 μg/ml).
CONCLUSION
The majority of Candida isolates grown as planktonic forms were susceptible to anidulafungin, caspofungin, conventional amphotericin B and fluconazole. Anidulafungin displayed higher activity against Candida biofilms than caspofungin. All Candida biofilms were resistant to fluconazole and conventional amphotericin B.
Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Biofilms; Blood Culture; Candida; Caspofungin; Echinocandins; Fluconazole; Hematologic Neoplasms; Humans; Microbial Sensitivity Tests; Plankton
PubMed: 34147758
DOI: 10.1016/j.mycmed.2021.101162 -
The Journal of Pharmacy and Pharmacology Dec 2017Echinocandins are the newest addition of the last decade to the antifungal armamentarium, which, owing to their unique mechanism of action, selectively target the fungal... (Comparative Study)
Comparative Study Review
OBJECTIVES
Echinocandins are the newest addition of the last decade to the antifungal armamentarium, which, owing to their unique mechanism of action, selectively target the fungal cells without affecting mammalian cells. Since the time of their introduction, they have come to occupy an important niche in the antifungal pharmacotherapy, due to their efficacy, safety, tolerability and favourable pharmacokinetic profiles. This review deals with the varying facets of echinocandins such as their chemistry, in-vitro and in-vivo evaluations, clinical utility and indications, pharmacokinetic and pharmacodynamic profiles, and pharmacoeconomic considerations.
KEY FINDINGS
Clinical studies have demonstrated that the echinocandins - caspofungin, micafungin and anidulafungin - are equivalent, if not superior, to the mainstay antifungal therapies involving amphotericin B and fluconazole. Moreover, echinocandin regimen has been shown to be more cost-effective and economical. Hence, the echinocandins have found favour in the management of invasive systemic fungal infections.
CONCLUSIONS
The subtle differences in echinocandins with respect to their pharmacology, clinical therapy and the mechanisms of resistance are emerging at a rapid pace from the current pool of research which could potentially aid in extending their utility in the fungal infections of the eye, heart and nervous system.
Topics: Anidulafungin; Animals; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Micafungin; Mycoses
PubMed: 28744860
DOI: 10.1111/jphp.12780