The opportunistic pathogen Candida parapsilosis is a major causative agent of candidiasis leading to death in immunocompromised individuals. Azoles are the first line of defense in their treatment. The purpose of this study was to characterize eight fluconazole-resistant and sensitive C. parapsilosis hospital isolates through a battery of phenotypic tests that target pathogenicity attributes such as virulence, biofilm formation, stress resistance, and ergosterol content. Whole genome sequencing was carried out to identify mutations in key pathogenicity and resistance genes. Phylogenetic comparison was performed to determine strain relatedness and clonality. Genomic data and phylogenetic analysis revealed that two isolates were C. orthopsilosis and C. metapsilosis misidentified as C. parapsilosis. Whole genome sequencing analysis revealed known and novel mutations in key drug resistance and pathogenicity genes such as ALS6, ALS7, SAPP3, SAP7, SAP9, CDR1, ERG6, ERG11 and UPC2. Phylogenetic analysis revealed a high degree of relatedness and clonality within our C. parapsilosis isolates. Our results showed that resistant isolates exhibited an increase in biofilm content compared to the sensitive isolates. In conclusion, our study is the first of its kind in Lebanon to describe phenotypic and genotypic characteristics of nosocomial C. parapsilosis complex isolates having a remarkable ability to form biofilms.
- MeSH
- antifungální látky * farmakologie MeSH
- biofilmy * růst a vývoj MeSH
- Candida parapsilosis * genetika izolace a purifikace klasifikace MeSH
- fenotyp * MeSH
- flukonazol farmakologie MeSH
- fungální léková rezistence * genetika MeSH
- fylogeneze * MeSH
- genotyp * MeSH
- infekce spojené se zdravotní péčí mikrobiologie MeSH
- kandidóza * mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- nemocnice MeSH
- sekvenování celého genomu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Libanon MeSH
Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.
- MeSH
- 3D tisk * MeSH
- farmaceutická technologie metody MeSH
- flukonazol * MeSH
- poréznost MeSH
- tablety chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). CONCLUSIONS: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.
- MeSH
- akutní myeloidní leukemie * farmakoterapie MeSH
- antifungální látky terapeutické užití MeSH
- flukonazol terapeutické užití MeSH
- kaspofungin terapeutické užití MeSH
- lidé MeSH
- myelodysplastické syndromy * MeSH
- mykózy * farmakoterapie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- Candida patogenita MeSH
- dospělí MeSH
- endoftalmitida * diagnóza etiologie farmakoterapie mikrobiologie MeSH
- flukonazol terapeutické užití MeSH
- imunokompromitovaný pacient MeSH
- lidé MeSH
- methotrexát farmakologie terapeutické užití MeSH
- oční infekce mykotické * diagnóza etiologie farmakoterapie mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.
Systemic fungal diseases and antifungal resistance represent a serious problem in human medicine and con-tribute to increased patient mortality. The most common causes of these diseases are opportunistic yeasts of the genus Candida. C. albicansis considered to be the main pathogen, together with C. glabrata, C. tropicalis, C. par-apsilosis, and C.krusei. Azole antifungals predominate in the treatment of the systemic mycoses. For antifungal re-sistance in Candidaspp. some genes and their mutations are responsible, the genes ERG11, CDR1, CDR2and MDR1being considered the most important. The main target of azole antifungals is the process of ergosterol syn-thesis. Due to ergosterol crucial functions and its unique structural properties, the synthesis of ergosterol and its individual steps represent the target of most clinically available antifungals. The biofilm appears to be a signifi-cant virulence factor of the yeast Candidaspp. It allows hematogenous dissemination of cells, prevents the effect of antifungals on all cells during treatment and leads to a high level of antimicrobial resistance. The antifungal re-sistance in candidiasis often has a multifactorial origin, which must be considered in the treatment of systemic mycoses and in the development of new antifungals.
- MeSH
- antifungální látky chemie farmakologie terapeutické užití MeSH
- azoly farmakologie terapeutické užití MeSH
- biofilmy účinky léků MeSH
- Candida patogenita účinky léků MeSH
- ergosterol biosyntéza MeSH
- faktory virulence MeSH
- flukonazol farmakologie terapeutické užití MeSH
- fungální léková rezistence MeSH
- itrakonazol farmakologie terapeutické užití MeSH
- kandidóza * farmakoterapie mikrobiologie MeSH
- lidé MeSH
- vorikonazol farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
Článek shrnuje základní poznatky o mykotickém zánětu v jícnu, pojednává o jeho původcích, rizikových faktorech, které jsou charakteristické pro toto onemocnění. Popisuje celkem typický endoskopický obraz při vyšetření horní části trávicí trubice, přičemž endoskopie je cennou diagnostickou metodou. Věnuje se i detailnímu popisu terapie mykotického infektu jícnu. Článek zahrnuje kazuistiku se zajímavým průběhem a obrazovou dokumentaci.
In the article, there is basic knowledge of mycotic esophagitis, it discusses etiological agents, risk factors that are characteristic for this type of infection. Describes quite a typical endoscopic image during the examination of the upper digestive system, while endoscopy is a valid method of the final diagnosis. It also pays attention to the therapy of mycotic esophagitis. The article includes case history with an interesting development and pictorial documents.
- MeSH
- antifungální látky MeSH
- ezofagitida * diagnóza farmakoterapie MeSH
- ezofágus diagnostické zobrazování patologie MeSH
- flukonazol aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mykózy * diagnóza farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- antifungální látky farmakologie terapeutické užití MeSH
- dospělí MeSH
- flukonazol farmakologie terapeutické užití MeSH
- kryptokoková meningitida * diagnóza farmakoterapie komplikace MeSH
- lidé MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, β, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. β-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.
- MeSH
- antifungální látky aplikace a dávkování terapeutické užití MeSH
- Candida albicans patogenita MeSH
- flukonazol aplikace a dávkování terapeutické užití MeSH
- kandidóza vulvovaginální diagnóza farmakoterapie MeSH
- klotrimazol aplikace a dávkování terapeutické užití MeSH
- mykózy * diagnóza etiologie farmakoterapie MeSH
