In vitro activities of anidulafungin and other antifungal agents against biofilms formed by clinical isolates of different Candida and Aspergillus species.
Ontology highlight
ABSTRACT:
SUBMITTER: Fiori B
PROVIDER: S-EPMC3101406 | biostudies-literature | 2011 Jun
REPOSITORIES: biostudies-literature
Publications
In vitro activities of anidulafungin and other antifungal agents against biofilms formed by clinical isolates of different Candida and Aspergillus species.
Fiori Barbara B Posteraro Brunella B Torelli Riccardo R Tumbarello Mario M Perlin David S DS Fadda Giovanni G Sanguinetti Maurizio M
Antimicrobial agents and chemotherapy 20110321 6
We tested the activities of anidulafungin and other antifungal agents against clinical isolates of different fungal species. For Candida species, high sessile MIC₉₀s (SMIC₉₀s) were obtained for fluconazole, voriconazole, and amphotericin B, whereas the anidulafungin SMIC₉₀s were very low, as were those for caspofungin. Comparatively, for Aspergillus species, higher SMIC₉₀ values were obtained not only for amphotericin B and voriconazole but also for the echinocandins. ...[more]
Similar Datasets
Project description:BackgroundCandida glabrata is a pathogenic yeast with several unique biological features and associated with an increased incidence rate of candidiasis. It exhibits a great degree of variation in its pathogenicity and antifungal susceptibility.ObjectivesThe aim of the present study was to evaluate the in vitro antifungal susceptibilities of the following six antifungal drugs against clinical C. glabrata strains: amphotericin B (AmB), ketoconazole (KTZ), fluconazole (FCZ), itraconazole (ITZ), voriconazole (VCZ), and caspofungin (CASP).Materials and methodsForty clinical C. glabrata strains were investigated using DNA sequencing. The in vitro antifungal susceptibility was determined as described in clinical laboratory standard institute (CLSI) documents (M27-A3 and M27-S4).ResultsThe sequence analysis of the isolate confirmed as C. glabrata and deposited on NCBI GenBank under the accession number no. KT763084-KT763123. The geometric mean MICs against all the tested strains were as follows, in increasing order: CASP (0.17 g/mL), VCZ (0.67 g/mL), AmB (1.1 g/mL), ITZ (1.82 g/mL), KTZ (1.85 g/mL), and FCZ (6.7 g/mL). The resistance rates of the isolates to CASP, FCZ, ITZ, VZ, KTZ, and AmB were 5%, 10%, 72.5%, 37.5%, 47.5%, and 27.5%, respectively.ConclusionsThese findings confirm that CASP, compared to the other antifungals, is the potent agent for treating candidiasis caused by C. glabrata. However, the clinical efficacy of these novel antifungals remains to be determined.
| S-EPMC4977912 | biostudies-literature
Project description:Monolaurin (also known as glycerol monolaurate) is a natural compound found in coconut oil and is known for its protective biological activities as an antimicrobial agent. The nature of oral candidiasis and the increased antifungal resistance demand the search for novel antifungal therapeutic agents. In this study, we examine the antifungal activity of monolaurin against Candida albicans biofilms (strain ATCC:SC5314/MYA2876) in vitro and investigate whether monolaurin can alter gene expression of host inflammatory cytokines, IL-1? and IL-1?. In a co-culture model, oral fibroblast cells were cultured simultaneously with C. albicans for 24 hrs followed by the exposure to treatments of monolaurin (3.9-2,500 µM), positive control fluconazole (32.2 µM), and vehicle control group (1% ethanol), which was a model used to evaluate the cytotoxicity of monolaurin on fibroblasts as well as to analyze morphological characteristics of biofilms through fluorescence microscopy. In addition, the co-culture model was used for RNA extraction of oral fibroblasts to assess gene expression of host inflammatory cytokines, using quantitative real-time PCR. Our results showed the MIC and MFC of monolaurin were in the range 62.5-125 µM and 125-250 µM, respectively. Biofilm antifungal assay showed significant reduction in Log (CFU/ml) of biofilms treated with 1,250 and 2,500 µM of 1-monolaurin when compared to the control groups . There was also a significant down-regulation of IL-1? and IL-1? in the co-culture treated with monolaurin. It can be concluded that monolaurin has a potential antifungal activity against C. albicans and can modulate the pro-inflammatory response of the host.
| S-EPMC4924139 | biostudies-literature
Project description:BackgroundThe voriconazole and echinocandin combination has been found to be synergistic in vitro and in vivo against most Aspergillus fumigatus isolates, both with a WT azole phenotype and an azole-resistant phenotype. The interaction between isavuconazole and echinocandins is less well studied. This is especially true for azole-resistant isolates.ObjectivesWe investigated the in vitro interaction between isavuconazole and anidulafungin for 30 A. fumigatus isolates including 18 azole-resistant isolates with various isavuconazole resistance phenotypes.MethodsThe isavuconazole/anidulafungin interaction was studied by using an adapted EUCAST-based 2D (12 × 8) chequerboard broth microdilution colorimetric assay using XTT. The interaction was analysed by FIC index (FICi) analysis and Bliss independence (BI) interaction analysis.ResultsBoth the FICi analysis and the BI analysis showed synergistic interaction between isavuconazole and anidulafungin for the majority of WT and azole-resistant isolates. As we did not see significant beneficial effects of combination therapy in TR46/Y121F/T289A isolates at clinically achievable drug concentrations, it is unlikely that TR46/Y121F/T289A infections would benefit from isavuconazole and anidulafungin combination therapy.ConclusionsIn regions with high azole resistance rates this combination may benefit patients with WT disease, azole-resistant invasive aspergillosis and those with mixed azole-susceptible and azole-resistant infection, but may not be beneficial for aspergillosis due to isolates with high isavuconazole resistance, such as TR46/Y121F/T289A isolates.
| S-EPMC7443724 | biostudies-literature
Project description:We determined the susceptibility of South African Candida auris bloodstream surveillance isolates to manogepix, a novel antifungal, and several registered antifungal agents. C. auris isolates were submitted to a reference laboratory between 2016 and 2017. Species identification was confirmed by phenotypic methods. We determined MICs for amphotericin B, anidulafungin, caspofungin, micafungin, itraconazole, posaconazole, voriconazole, fluconazole, and flucytosine using Sensititre YeastOne and manogepix using a modified Clinical and Laboratory Standards Institute broth microdilution method. Clade distribution was determined for a subset of isolates using whole-genome sequencing. Of 394 tested isolates, 357 were resistant to at least 1 antifungal class. The manogepix MIC range was 0.002 to 0.06 μg/mL for 335 isolates with fluconazole monoresistance. Nineteen isolates were resistant to both fluconazole and amphotericin B yet still had low manogepix MICs (range, 0.004 to 0.03 μg/mL). Two isolates from the same patient were panresistant but had manogepix MICs of 0.004 μg/mL and 0.008 μg/mL. Comparing MIC50 values, manogepix was >3-fold more potent than azoles, 4-fold more potent than echinocandins, and 9-fold more potent than amphotericin B. Of 84 sequenced isolates, the manogepix MIC range for 70 clade III isolates was 0.002 to 0.031 μg/mL, for 13 clade I isolates was 0.008 to 0.031 μg/mL, and for one clade IV isolate, 0.016 μg/mL. Manogepix exhibited potent activity against all isolates, including those resistant to more than one antifungal agent and in three different clades. These data support manogepix as a promising candidate for treatment of C. auris infections. IMPORTANCE Since C. auris was first detected in South Africa in 2012, health care-associated transmission events and large outbreaks have led to this pathogen accounting for more than 1 in 10 cases of candidemia. A large proportion of South African C. auris isolates are highly resistant to fluconazole but variably resistant to amphotericin B and echinocandins. There is also an emergence of pandrug-resistant C. auris isolates, limiting treatment options. Therefore, the development of new antifungal agents such as fosmanogepix or the use of new combinations of antifungal agents is imperative to the continued effective treatment of C. auris infections. Manogepix, the active moiety of fosmanogepix, has shown excellent activity against C. auris isolates. With the emergence of C. auris isolates that are pandrug-resistant in South Africa, our in vitro susceptibility data support manogepix as a promising new drug candidate for treatment of C. auris and difficult-to-treat C. auris infections.
| S-EPMC8865435 | biostudies-literature
Project description:In this study, we investigated the potential antifungal activity of the alkylphospholipid oleylphosphocholine (OlPC), a structural analogue of miltefosine, on in vitro and in vivoCandida albicans biofilm formation. The effect of OlPC on in vitro and in vivoC. albicans biofilms inside triple-lumen polyurethane catheters was studied. In vivo biofilms were developed subcutaneously after catheter implantation on the lower back of Sprague-Dawley rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7 days. The effect of OlPC on biofilms that developed on the mucosal surface was studied in an ex vivo model of oral candidiasis. The role of OlPC in C. albicans morphogenesis was investigated by using hypha-inducing media, namely, Lee, Spider, and RPMI 1640 media. OlPC displayed activity against both planktonic cells and in vitroC. albicans biofilms. To completely abolish preformed, 24-h-old biofilms, higher concentrations (8, 10, and 13 mg/liter) were needed. Moreover, OlPC was able to reduce C. albicans biofilms formed by caspofungin-resistant clinical isolates and acted synergistically when combined with caspofungin. The daily oral administration of OlPC significantly reduced in vivoC. albicans biofilms that developed subcutaneously. In addition, OlPC decreased biofilm formation on mucosal surfaces. Interestingly, the application of subinhibitory concentrations of OlPC already inhibited the yeast-to-hypha transition, a crucial virulence factor of C. albicans We document, for the first time, the effects of OlPC on C. albicans cells and suggest the potential use of OlPC for the treatment of C. albicans biofilm-associated infections.
| S-EPMC5740347 | biostudies-literature
Project description:Echinocandins are the recommended first-line antifungals for treatment of invasive candidiasis. The increasing number of Candida glabrata strains resistant against echinocandins is an emerging health care concern. The rapid detection of resistant C. glabrata isolates is an urgent requirement for clinical laboratories. In this study, we developed the MALDI Biotyper antibiotic (antifungal) susceptibility test rapid assay (MBT ASTRA) for the rapid detection of anidulafungin-resistant C. glabrata isolates directly from positive blood cultures. Of 100 C. glabrata strains, MBT ASTRA classified 69 as susceptible and 29 as resistant. Microdilution assays performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, used as a standard reference, identified 65 susceptible, 9 intermediate, and 26 resistant isolates. Sequencing of hot spot 1 and hot spot 2 regions of the FKS1 and FKS2 genes classified 86 susceptible and 14 resistant isolates. The MBT ASTRA had sensitivity and specificity of 80% and 95%, respectively, compared to the microdilution method. Positive and negative agreement of MBT ASTRA was calculated at 100% and 80%, respectively, compared with the molecular sequencing approach. Together, these results revealed a high accuracy of MBT ASTRA compared to microdilution according to the CLSI and PCR analysis, resulting in a categorical agreement of 90% and 83%, respectively. The validity of MBT ASTRA was 98%. Importantly, MBT ASTRA provided antifungal susceptibility testing (AFST) within 6 h that was both accurate and reliable compared to the other two approaches, which require at least 24 h or are costly. Therefore, this method has the potential to facilitate clinical AFST rapidly at low sample costs for clinical labs already equipped with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).
| S-EPMC6709499 | biostudies-literature
Project description:The development of yeast biofilms is a major problem due to their increased antifungal resistance, which leads to persistent infections with severe clinical implications. The high antifungal activity of well-characterized chitosan polymers makes them potential alternatives for treating yeast biofilms. The activity of a chito-oligosaccharide with a depolymerization degree (DPn) of 32 (C32) and a fraction of acetylation (FA) of 0.15 on Candida sp. biofilms was studied. The results showed a concentration-dependent reduction in the number of viable cells present in C. albicans, C. glabrata, and C. guillermondii preformed biofilms in the presence of C32, especially on intermediate and mature biofilms. A significant decrease in the metabolic activity of yeast biofilms treated with C32 was also observed. The antifungals fluconazole (Flu) and miconazole (Mcz) decreased the number of viable cells in preformed early biofilms, but not in the intermediate or mature biofilms. Contrary to Flu or Mcz, C32 also reduced the formation of new biofilms. Interestingly, a synergistic effect on yeast biofilm was observed when C32 and Flu/Mcz were used in combination. C32 has the potential to become an alternative therapeutic agent against Candida biofilms alone or in combination with antifungal drugs and this will reduce the use of antifungals and decrease antifungal resistance.
| S-EPMC8464920 | biostudies-literature
Project description:Therapies targeted to fungal biofilms, mainly against the matrix, and therapies that do not induce microbial resistance are relevant. N-acetylcysteine (NAC), a mucolytic agent, has shown antimicrobial action. This study evaluated the effect of NAC against fluconazole-susceptible (CaS) and -resistant (CaR) Candida albicans. The susceptibility of planktonic cultures to NAC, the effect of NAC on biofilms and their matrix, the interaction of NAC with antifungal agents, and confocal microscopy were evaluated. Data were analyzed descriptively and by the ANOVA/Welch and Tukey/Gomes-Howell tests. The minimum inhibitory concentration (MIC) of NAC was 25 mg/mL for both strains. NAC significantly reduced the viability of both fungal strains. Concentrations higher than the MIC (100 and 50 mg/mL) reduced the viability and the biomass. NAC at 12.5 mg/mL increased the fungal viability. NAC also reduced the soluble components of the biofilm matrix, and showed synergism with caspofungin against planktonic cultures of CaS, but not against biofilms. Confocal images demonstrated that NAC reduced the biofilm thickness and the fluorescence intensity of most fluorochromes used. High concentrations of NAC had similar fungistatic effects against both strains, while a low concentration showed the opposite result. The antibiofilm action of NAC was due to its fungistatic action.
| S-EPMC7409114 | biostudies-literature
Project description:ObjectivesMicrobial adhesion and biofilms have important implications for human health and disease. Candida albicans is an opportunistic pathogen which forms drug-resistant biofilms that contribute to the recalcitrance of disease. We have developed a high-throughput screen for potentiators of clotrimazole, a common therapy for Candida infections, including vaginitis and thrush. The screen was performed against C. albicans biofilms grown in microtitre plates in order to target the most resilient forms of the pathogen.MethodsBiofilm growth, in individual wells of 384-well plates, was measured using the metabolic indicator alamarBlue® and found to be very consistent and reproducible. This assay was used to test the effect of more than 120 000 small molecule compounds from the NIH Molecular Libraries Small Molecule Repository, and compounds that enhanced the activity of clotrimazole or acted on the biofilms alone were identified as hits.ResultsNineteen compounds (0.016% hit rate) were identified and found to cause more than 30% metabolic inhibition of biofilms compared with clotrimazole alone, which had a modest effect on biofilm viability at the concentration tested. Hits were confirmed for activity against biofilms with dose-response measurements. Several compounds had increased activity in combination with clotrimazole, including a 1,3-benzothiazole scaffold that exhibited a >100-fold improvement against biofilms of three separate C. albicans isolates. Cytotoxicity experiments using human fibroblasts confirmed the presence of lead molecules with favourable antifungal activity relative to cytotoxicity.ConclusionsWe have validated a novel approach to identify antifungal potentiators and completed a high-throughput screen to identify small molecules with activity against C. albicans biofilms. These small molecules may specifically target the biofilm and make currently available antifungals more effective.
| S-EPMC3058565 | biostudies-literature
Project description:We recently observed that the micafungin MICs for some Candida glabrata fks hot spot mutant isolates are less elevated than those for the other echinocandins, suggesting that the efficacy of micafungin may be differentially dependent on such mutations. Three clinical C. glabrata isolates with or without (S3) fks hot spot mutations R83 (Fks2p-S663F) and RR24 (Fks1p-S629P) and low, medium, and high echinocandin MICs, respectively, were evaluated to assess the in vivo efficacy in an immunocompetent mouse model using three doses of each echinocandin. Drug concentrations were determined in plasma and kidneys by high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic mathematical model was used to define the area under the concentration-time curve (AUC) that produced half- and near-maximal activity. Micafungin was equally efficacious against the S3 and R83 isolates. The estimates for the AUCs of each echinocandin that induced half-maximal effect (E(50)s) were 194.2 and 53.99 mg · h/liter, respectively. In contrast, the maximum effect (E(max)) for caspofungin was higher against S3 than R83, but the estimates for E(50) were similar (187.1 and 203.5 mg · h/liter, respectively). Anidulafungin failed to induce a ≥1-log reduction for any of the isolates (AUC range, 139 to 557 mg · h/liter). None of the echinocandins were efficacious in mice challenged with the RR24 isolate despite lower virulence (reduced maximal growth, prolonged lag phase, and lower kidney burden). The AUC associated with half-maximal effect was higher than the average human exposure for all drug-dose-bug combinations except micafungin and the R83 isolate. In conclusion, differences in micafungin MICs are associated with differential antifungal activities in the animal model. This study may have implications for clinical practice and echinocandin breakpoint determination, and further studies are warranted.
| S-EPMC3346593 | biostudies-literature