Micafungin 100mg powder for solution for infusion vials

BACKGROUND: Micafungin, Amphotericin B, and Fluconazole are the primary therapeutic agents employed to address invasive fungal candidiasis in neonates. Resistance to fluconazole is gradually developing in neonatal intensive care units. We aimed to conduct a comparative analysis of Micafungin and Amphotericin B in terms of their effectiveness and safety in the treatment of invasive fungal infections in neonates. METHODS: Fifty-six preterm neonates with invasive fungal infection proven by fungal culture and who had received fluconazole for at least one week were included in our study and were divided randomly into two groups. Micafungin group: twenty-eight preterms received Micafungin at a dose of 8 mg/kg/day for 14 days. Amphotericin B group: twenty-eight preterms received amphotericin B at a dose of 1 mg /kg/day for 14 days. Clinical and laboratory follow up by fungal culture were performed after 14 days. RESULTS: Neonates in the Micafungin group showed significant increased percentage for complete cure of the fungal infection compared to Amphotericin B group 18(64.3%) vs. 10(35.7%) respectively and decreased percentage of incomplete cure 10(35.7%) vs. 18(64.3%) respectively with p-value 0.030. A higher percentage of neonates were completely cured for both candida albicans (65.2%) and non-albicans (60%) in the micafungin group. Duration of respiratory and circulatory support was significantly shorter also. No additional drug side effects were observed with Micafungin except for mild hypomagnesemia. There was an increase in blood urea nitrogen with Amphotericin B. CONCLUSION: Micafungin is effective and well tolerated for the treatment of invasive fungal infections in preterm neonates. TRIAL REGISTRATION: The current study was approved by clinicaltrials.org and the protocol ID NCT06413056 was retrospectively registered in on 11th of march 2024. https://clinicaltrials.gov/study/NCT06413056?cond=micafungin%20in%20neonates&rank=2 .

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In recent years, many population pharmacokinetic (popPK) models have been developed for echinocandins to better understand the pharmacokinetics (PK) of these antifungals. This comprehensive review aimed to summarize popPK models of echinocandins (micafungin, caspofungin, anidulafungin, and rezafungin), by focusing on dosage optimization to maximize the probability of attaining the PK/PD target proposed in special populations. A search in PubMed, Embase, Web of Science, and Scopus, supplemented by the bibliography of relevant articles, was conducted from inception to March 2024, including both observational and prospective trials. A total of 1126 articles were identified, 47 of them were included in the review (22 for micafungin, 13 for caspofungin, 9 for anidulafungin, and 3 for rezafungin). A two-compartment model was more frequently used to describe the PK parameters of echinocandin (78.7% of developed models), although more complex structural models with three and four compartments have also been developed. The covariates to estimate the PK parameters such as clearance (CL) and volume of distribution (Vd) differed between models. Weight total (WT) was the most frequently reported to be a significant predictor for both parameters, especially for estimating the CL in pediatrics. The PD parameter most widely reported assessing the drug exposure–efficacy relationship was the area under the concentration–time curve to minimum inhibitory concentration (MIC) ratio (AUC0–24/MIC) with different targets proposed for each echinocandin. In certain populations such as patients that are critically ill, obese, receiving extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), or pediatric patients and/or patients with cancer or that are immunocompromised, the fixed dosing strategies recommended in the drug prescribing information may not reach the PK/PD target. For these populations, different strategies have been proposed, such as a dosing regimen based on body weight or increasing the loading and/or maintenance dose. Despite echinocandins’ favorable safety profile and predictable PK, certain groups at risk of suboptimal drug exposure can benefit from therapeutic drug monitoring (TDM) to prevent clinical failures. Numerous popPK models of echinocandins have been developed. However, an external validation of the suggested dosing regimens in conjunction with an analysis of population subgroups should be conducted before implementing a popPK model in clinical practice.

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Candida ( Clavispora ) lusitaniae is a rare, emerging non- albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood.

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The prevalence of antibiotic resistance in Pseudomonas aeruginosa places a heavy burden on the health care sectors urging the need to find alternative, non-antibiotic strategies. The interference with the P. aeruginosa quorum sensing (QS) system represents a promising alternative strategy to attenuate the bacterial virulency and its ability to form biofilms. Micafungin has been reported to impede the pseudomonal biofilm formation. However, the influences of micafungin on the biochemical composition and metabolites levels of P. aeruginosa have not been explored. In this study, the effect of micafungin (100 µg/mL) on the virulence factors, QS signal molecules and the metabolome of P. aeruginosa was studied using exofactor assay and mass spectrometry-based metabolomics approaches. Furthermore, confocal laser scanning microscopy (CLSM) using the fluorescent dyes ConA-FITC and SYPRO® Ruby was used to visualize micafungin disturbing effects on the pseudomonal glycocalyx and protein biofilm-constituents, respectively. Our findings showed that micafungin significantly decreased the production of various QS-controlled virulence factors (pyocyanin, pyoverdine, pyochelin and rhamnolipid), along with a dysregulation in the level of various metabolites involved in QS system, lysine degradation, tryptophan biosynthesis, TCA cycle, and biotin metabolism. In addition, the CLSM examination showed an altered matrix distribution. The presented findings highlight the promising role of micafungin as a potential quorum sensing inhibitor (QSI) and anti-biofilm agent to attenuate P. aeruginosa pathogenicity. In addition, they point to the promising role of metabolomics study in investigating the altered biochemical pathways in P. aeruginosa.

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BACKGROUND: Micafungin is an echinocandin-type antifungal agent used for the clinical treatment of invasive fungal infections. It is semisynthesized from the sulfonated lipohexapeptide FR901379, a nonribosomal peptide produced by the filamentous fungus Coleophoma empetri. However, the low fermentation efficiency of FR901379 increases the cost of micafungin production and hinders its widespread clinical application. RESULTS: Here, a highly efficient FR901379-producing strain was constructed via systems metabolic engineering in C. empetri MEFC09. First, the biosynthesis pathway of FR901379 was optimized by overexpressing the rate-limiting enzymes cytochrome P450 McfF and McfH, which successfully eliminated the accumulation of unwanted byproducts and increased the production of FR901379. Then, the functions of putative self-resistance genes encoding β-1,3-glucan synthase were evaluated in vivo. The deletion of CEfks1 affected growth and resulted in more spherical cells. Additionally, the transcriptional activator McfJ for the regulation of FR901379 biosynthesis was identified and applied in metabolic engineering. Overexpressing mcfJ markedly increased the production of FR901379 from 0.3 g/L to 1.3 g/L. Finally, the engineered strain coexpressing mcfJ, mcfF, and mcfH was constructed for additive effects, and the FR901379 titer reached 4.0 g/L under fed-batch conditions in a 5 L bioreactor. CONCLUSIONS: This study represents a significant improvement for the production of FR901379 and provides guidance for the establishment of efficient fungal cell factories for other echinocandins.

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Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC50) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC50) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.

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