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International Journal of Antimicrobial... Aug 2022Invasive candidiasis is the most common fungal infection in patients attending health services and is associated with high mortality rates and prolonged hospital stay.... (Meta-Analysis)
Meta-Analysis
AIM
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.
METHODS
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.
RESULTS
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%).
CONCLUSION
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
PubMed: 35691603
DOI: 10.1016/j.ijantimicag.2022.106614 -
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 -
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 -
Revista Iberoamericana de Micologia Mar 2009Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been... (Review)
Review
BACKGROUND
Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Although several new antifungal agents have been developed in the past few years, the management of serious fungal infections continues to be problematic.
AIMS
To review the pharmacodynamics and pharmacokinetics of a new antifungal agent: micafungin.
METHODS
A systematic review of biomedic databases (EBSCO Open Journals, Ovid Online, Proquest Medical Library, PubMed/Medline, Science Direct, Springer Links and Wiley Interscience) has been performed. Search was conducted from 2000 to 2008. Supplementary sources included abstracts from the Interscience Conference on Antimicrobial Agents (ICAAC) and Chemotherapy and the Infectious Diseases Society of America (IDSA) from 1998 to 2008.
RESULTS
Micafungin has a potent mechanism of action: inhibits beta-1,3-D-glucan synthase interfering with fungal cell wall synthesis. This agent shares with caspofungin an identical spectrum of in vitro activity against Candida albicans, non-albicans Candida species, and Aspergillus. Due to the limited oral availability, micafungin is available for parenteral administration only. Micafungin is characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions have been described. No dose reduction is required in renal impairment or in mild to moderate liver failure.
CONCLUSIONS
The pharmacodynamic and pharmacokinetic profiles of micafungin imply that this drug is a safe alternative for the treatment of fungal infections. Micafungin can be safely co-administered with most drugs without the need for dosage adaptation even in patients with renal o liver function impairment.
Topics: Adolescent; Adult; Aged; Animals; Antifungal Agents; Aspergillus; Biotransformation; Candida; Child; Child, Preschool; Drug Evaluation, Preclinical; Drug Interactions; Echinocandins; Fungal Proteins; Glucosyltransferases; Humans; Infant, Newborn; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Middle Aged; Molecular Structure; Mycoses; Pneumocystis carinii; Young Adult
PubMed: 19463274
DOI: 10.1016/S1130-1406(09)70005-1 -
Mayo Clinic Proceedings Sep 2008To compare available antifungal treatments for invasive candidiasis, a leading cause of nosocomial bloodstream infections. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare available antifungal treatments for invasive candidiasis, a leading cause of nosocomial bloodstream infections.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials that compared different antifungal agents for the treatment of candidemia and other forms of invasive candidiasis. Two reviewers independently appraised the quality of trials and extracted data. The primary outcome was all-cause mortality, and secondary outcomes were microbiological failure, treatment failure, and adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled.
RESULTS
Of the 15 included trials, 9 compared fluconazole with other drugs (amphotericin B, itraconazole, or a combination of fluconazole and amphotericin B), 4 compared echinocandins with other drugs (fluconazole, amphotericin B, liposomal amphotericin B), 1 compared micafungin and caspofungin, and 1 compared amphotericin B plus fluconazole and voriconazole. No difference in mortality was observed with fluconazole vs amphotericin B (RR, 0.92; 95% CI, 0.72-1.17); however, the rate of microbiological failure increased in the fluconazole arm (RR, 1.52; 95% CI, 1.12-2.07). Anidulafungin decreased the rate of microbiological failure compared with fluconazole (RR, 0.50; 95% CI, 0.29-0.86) with fewer adverse events. Caspofungin was comparable to amphotericin B in mortality and efficacy, with fewer adverse events requiring discontinuation (RR, 0.11; 95% CI, 0.04-0.36). Micafungin was comparable to liposomal amphotericin B in mortality.
CONCLUSION
All assessed antifungal agents showed similar efficacy, but the rate of microbiological failure increased with fluconazole vs amphotericin B or anidulafungin. Amphotericin B is associated with a higher rate of adverse events than fluconazole and echinocandins.
Topics: Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Confidence Intervals; Drug Therapy, Combination; Echinocandins; Fluconazole; Humans; Itraconazole; Lipopeptides; Lipoproteins; Micafungin; Odds Ratio; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole
PubMed: 18775201
DOI: 10.4065/83.9.1011 -
American Journal of Transplantation :... Dec 2014Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A... (Meta-Analysis)
Meta-Analysis Review
Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A comprehensive literature search was performed to identify randomized controlled trials comparing regimens for antifungal prophylaxis in liver transplant recipients. Direct comparisons were made between treatments using random-effects meta-analysis and a Bayesian network meta-analysis was performed for the primary end point of proven IFI. Fourteen studies met inclusion criteria, reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB), itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause mortality was not significantly affected. There was no difference in risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB reduces the incidence of IFI following liver transplantation, and the available evidence suggests that the two are equivalent in efficacy.
Topics: Antibiotic Prophylaxis; Antifungal Agents; Graft Rejection; Humans; Liver Diseases; Liver Transplantation; Mycoses; Postoperative Complications
PubMed: 25395336
DOI: 10.1111/ajt.12925 -
Mycoses Sep 2019Candida resistance to antifungals impaired invasive candidiasis outcome. In a context of echinocandin resistance development, we aimed to evaluate the association... (Meta-Analysis)
Meta-Analysis
Comparison of fks gene mutations and minimum inhibitory concentrations for the detection of Candida glabrata resistance to micafungin: A systematic review and meta-analysis.
Candida resistance to antifungals impaired invasive candidiasis outcome. In a context of echinocandin resistance development, we aimed to evaluate the association between phenotypic resistance to micafungin and fks mutations of Candida glabrata. For this systematic review and meta-analysis, we searched MEDLINE, Scopus and Web of Science for reports published up to December 2017. Studies of C glabrata candidiasis with minimum inhibitory concentrations (MIC) determination of micafungin and fks genotyping were included. Reviews, studies not using reference methods, non-glabrata Candida, experimental isolates and undetailed mutations were excluded. Two authors independently assessed the eligibility of articles and extracted data. The main outcome was the diagnostic accuracy of fks mutations compared to micafungin MIC for C glabrata, measured as fixed-effect odd ratio. Heterogeneity was calculated with the I statistic. This study is registered with PROSPERO (CRD42018082023). Twenty-four studies were included in the meta-analysis. Pooled analysis found that S663P (OR 7.25, 95% CI 3.50-15.00; P < 0.00001), S629P (OR 3.70, 1.64-8.33; P = 0.002) and F659del (OR 5.66, 1.22-26.18; P = 0.03) were associated with increased risk of having a resistant isolate according to authors' interpretation of MICs. In sensitivity analysis based on new CLSI clinical breakpoints, the ORs for S663P and S629P remained significant. Genotyping of isolates of C glabrata for S663P and S629P mutations is an effective alternative to micafungin susceptibility tests. Relevant molecular markers of drug resistance will significantly improve the management of C glabrata infections.
Topics: Antifungal Agents; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Fungal Proteins; Genotype; Humans; Micafungin; Microbial Sensitivity Tests; Mutation
PubMed: 31077631
DOI: 10.1111/myc.12929 -
BMC Infectious Diseases Nov 2020Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris.
METHODS
We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0.
RESULTS
It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%).
CONCLUSIONS
Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.
Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidiasis; Caspofungin; Drug Resistance, Multiple, Fungal; Fluconazole; Humans; Micafungin; Prevalence
PubMed: 33176724
DOI: 10.1186/s12879-020-05543-0 -
Frontiers in Pharmacology 2021Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the... (Review)
Review
Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the therapeutic effects of these drugs on IFI have been well documented, the long-term use of antifungal agents has raised concerns about drug tolerability and treatment-related toxicity risks. We searched articles published before June 30, 2020 in four electronic databases: Web of Science, Cochrane Library, embase and PubMed. 66 trials were determined to meet our inclusion criteria, providing data on 18,230 participants. We sorted out 23 AEs by system organ classes and six laboratory AEs, 13 of these were used to construct 13 network meta-analyses. Compared with LAmB, anidulafungin, caspofungin, micafungin, fluconazole, and posaconazole had a significantly low incidence of discontinuation of therapy due to AEs (OR = 0.24 (0.09,0.65), 0.24 (0.13,0.43), 0.32 (0.19,0.52), 0.38 (0.23,0.62) and 0.35 (0.17,0.69), respectively). We found that echinocandins are the most tolerated antifungal agents with high safety. The AEs of triazole drugs are mainly concentrated on the increase in liver enzymes, nervous system disorders, especially visual disorders, gastrointestinal disorders, and cardiac diseases. LAmB is the least tolerated and has the most abundant AEs.
PubMed: 34776941
DOI: 10.3389/fphar.2021.697330 -
Critical Care Medicine Nov 2017The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection.
DATA SOURCES
A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed.
STUDY SELECTION
Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials.gov, as well as reference lists.
DATA EXTRACTION
The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs.
DATA SYNTHESIS
Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74-1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35-0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19-1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection.
CONCLUSIONS
Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.
Topics: Antifungal Agents; Candidiasis; Critical Illness; Hospital Mortality; Humans; Immunocompromised Host; Intensive Care Units; Randomized Controlled Trials as Topic
PubMed: 28857851
DOI: 10.1097/CCM.0000000000002698