-
Pharmaceutics Oct 2022Aspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing...
Evaluation of the Sensititre YeastOne and Etest in Comparison with CLSI M38-A2 for Antifungal Susceptibility Testing of Three Azoles, Amphotericin B, Caspofungin, and Anidulafungin, against and Other Species, Using New Clinical Breakpoints and Epidemiological Cutoff Values.
Aspergillosis is an invasive fungal disease associated with high mortality. Antifungal susceptibility testing (AFST) is receiving increasing consideration for managing patients, as well as for surveilling emerging drug resistance, despite having time-consuming and technically complex reference methodologies. The Sensititre YeastOne (SYO) and Etest methods are widely utilized for yeasts but have not been extensively evaluated for Aspergillus isolates. We obtained Posaconazole (POS), Voriconazole (VCZ), Itraconazole (ITC), Amphotericin B (AMB), Caspofungin (CAS), and Anidulafungin (AND) minimum inhibitory concentrations (MICs) for both the Etest (n = 330) and SYO (n = 339) methods for 106 sequenced clinical strains. For 84 A. fumigatus, we analyzed the performance of both commercial methods in comparison with the CLSI-AFST, using available cutoff values. An excellent correlation could be demonstrated for Etest-AMB and Etest-VCZ (p < 0.01). SYO-MICs of AMB, VCZ, and POS resulted in excellent essential agreement (>93%), and >80% for AMB, VCZ, and ITC Etest-MICs. High categoric agreement was found for AMB, ITC, and CAS Etest-MICs (>85%) and AMB SYO-MICs (>90%). The considerable number of major/very major errors found using Etest and SYO, possibly related to the proposed cutoffs and associated with the less time-consuming processes, support the need for the improvement of commercial methods for Aspergillus strains.
PubMed: 36297597
DOI: 10.3390/pharmaceutics14102161 -
BMC Oral Health Apr 2023Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral... (Observational Study)
Observational Study
BACKGROUND
Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity.
METHODS
An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014-2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied.
RESULTS
Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2-3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin.
CONCLUSION
C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer.
TRAIL REGISTRATION
The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.
Topics: Humans; Candidiasis, Oral; Fluconazole; Amphotericin B; Anidulafungin; Microbial Sensitivity Tests; Antifungal Agents; Candida; Candida albicans; Neoplasms; Drug Resistance, Fungal
PubMed: 37072843
DOI: 10.1186/s12903-023-02950-y -
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 -
Farmacia Hospitalaria : Organo Oficial... Sep 2019To determine by experimentation whether micafungin and anidulafungin possess physicochemical properties suitable for nebulization.
OBJECTIVE
To determine by experimentation whether micafungin and anidulafungin possess physicochemical properties suitable for nebulization.
METHOD
PH, osmolality, viscosity, density and chloride content were determined by pH monitoring, osmometry, viscometry, densitometry and potentiometry in two samples of different concentrations, 5 and 10 mg/mL each echinocandin. Results: The results obtained for micafungin solution were: pH 5.80 (0.14), osmolality 293.33 (1.53) mOsm/kg, chloride content 134.67 (0.58) mmol/L and density 1,009.4 (0,1) kg/m3; while for 10 mg/mL solution: osmolality 342.00 (1.00) mOsm/kg, chloride content 139.67 (0.58) mmol/L and density 1,014.5 (0.2) kg/m3. The results obtained for 5 mg/mL anidulafungin were: pH 4.22 (0.01), osmolality 464.67 (2.52) mOsm/kg, chloride content 137.00 (0.00) mmol/L and density 1,016.5 (0,2) kg/m3; while for 10 mg/mL solution: osmolality 656.33 (1.15) mOsm/kg, chloride content 132.00 (0.00) mmol/L and density 1,029.8 (0.4) kg/m3. Conclusions: PH, osmolality, chloride content and density values proved to be suitable for proper tolerability by nebulization.
Topics: Administration, Inhalation; Anidulafungin; Antifungal Agents; Chlorides; Humans; Hydrogen-Ion Concentration; Micafungin; Nebulizers and Vaporizers; Osmometry; Viscosity
PubMed: 31469629
DOI: 10.7399/fh.11226 -
Pharmacokinetics of echinocandins in suspected candida peritonitis: A potential risk for resistance.International Journal of Infectious... Dec 2020A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.
INTRODUCTION
A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid.
MATERIALS/METHODS
Peritoneal and serum concentrations of caspofungin, micafungin and anidulafungin were analysed in surgical patients with suspected candida peritonitis. After 4 days of starting therapy, serum and peritoneal samples (through peritoneal drainage) were obtained at baseline, 1, 6, 12 and 24 h of drug administration. Micafungin and anidulafungin concentrations were determined using high-performance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay.
RESULTS
Twenty-three critically ill patients with suspected abdominal fungal infection who were receiving an echinocandin were prospectively recruited. No specific criteria were applied to prescribe one specific echinocandin. No special clinical differences were observed among the three groups of patients. All were receiving antibiotic therapy, 80% required inotropic drugs, and fungal peritonitis was confirmed in 74% of them. The AUC (mg × h/L) obtained in serum and peritoneal fluid were: 126.84 and 34.38, 98.52 and 18.83, and 66.9 and 8.78 for anidulafungin, micafungin and caspofungin, respectively. The median concentration in peritoneal fluid ranged from 0.66 to 1.82 μg/mL for anidulafungin, 0.68-0.88 μg/mL for micafungin and 0.21-0.46 μg/mL for caspofungin.
CONCLUSION
The results showed moderate penetration of echinocandins into the peritoneal fluid of these patients. These levels are below the threshold of resistance mutant selection published by other authors. This could justify a potential risk of resistance in patients with prolonged treatment with echinocandins and suboptimal control of abdominal infection.
Topics: Adult; Anidulafungin; Antifungal Agents; Candida glabrata; Candidiasis; Caspofungin; Critical Illness; Echinocandins; Female; Humans; Male; Micafungin; Microbial Sensitivity Tests; Peritonitis; Prospective Studies
PubMed: 32937195
DOI: 10.1016/j.ijid.2020.09.019 -
Antimicrobial Agents and Chemotherapy Mar 2021A total of 15 isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation...
Evaluation of Synergistic Activity of Isavuconazole or Voriconazole plus Anidulafungin and the Occurrence and Genetic Characterization of Candida auris Detected in a Surveillance Program.
A total of 15 isolates from the SENTRY antimicrobial surveillance program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed for genetic relatedness and resistance mechanisms. Applying the tentative statistical epidemiological cutoff values and the Centers for Disease Control tentative breakpoints, 32/36 isolates were resistant to fluconazole, 5/36 were resistant to amphotericin B, 5/36 were non-wild-type (NWT) to anidulafungin, 3/36 were NWT to micafungin, and 1/36 and 10/36 were NWT to isavuconazole and voriconazole, respectively. Of these, 10 isolates were multidrug resistant, which means that these isolates were resistant to 2 antifungal classes. Synergy or partial synergy was noted in 5/36 and 22/36, respectively, of the isolates with the combination of anidulafungin plus voriconazole, and 11/36 and 19/36 isolates, respectively, for the combination of anidulafungin plus isavuconazole. Multilocus sequence type (MLST) analysis of the 15 SENTRY isolates demonstrated that the isolates from the US were genetically related to, but different from, isolates from Latin America (Panama and Colombia) and Germany. Single nucleotide polymorphism (SNP) analysis showed that the 15 SENTRY isolates belonged to the described international clades and had associated Erg11 alterations, including 11 isolates displaying K143R, one displaying F126L, and one displaying Y501H alterations and a fluconazole MIC result of ≥64 mg/liter. Resistance mechanisms were not observed in the two isolates displaying fluconazole MIC values at 4 and 16 mg/liter. Isavuconazole displayed activity and greater synergy when tested with anidulafungin than seen with anidulafungin plus voriconazole against the clinical isolates that displayed resistance phenotypes.
Topics: Anidulafungin; Antifungal Agents; Candida; Colombia; Drug Resistance, Fungal; Drug Synergism; Echinocandins; Germany; Microbial Sensitivity Tests; Multilocus Sequence Typing; Nitriles; Pyridines; Triazoles; Voriconazole
PubMed: 33431416
DOI: 10.1128/AAC.02031-20 -
The Journal of Antimicrobial... Apr 2017Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal...
OBJECTIVES
Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia.
METHODS
These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™.
RESULTS
A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance.
CONCLUSIONS
We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.
Topics: Anidulafungin; Antifungal Agents; Australia; Azoles; Candida; Candida glabrata; Candida tropicalis; Candidemia; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Humans; Incidence; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Triazoles; Voriconazole
PubMed: 28364558
DOI: 10.1093/jac/dkw422 -
Indian Journal of Microbiology Mar 2022Fungi are one of the most widely distributed microorganisms in the environment, including food such as fruits, vegetables and other crops, posing a potential threat to...
Fungi are one of the most widely distributed microorganisms in the environment, including food such as fruits, vegetables and other crops, posing a potential threat to food safety and human health. The aim of this study was to determine the diversity, intensity and drug resistance of potentially pathogenic filamentous fungi isolated from the fresh raspberries ( L.). A total of 50 strains belonging to genera , , , , , , and were tested for drug resistance against 11 antifungals by disc diffusion and gradient strips methods. The average mycological contamination in the examined samples of raspberries amounted to 4.34 log CFU/g. The was isolated from all tested samples, followed by and with a frequency of 61% and 34%, respectively. The highest level of drug resistance was observed for genera and strains recorded a wide variation in drug resistance as revealed by susceptibility with amphotericin B and voriconzole with MICs ranged from 0.5-4 µg/ml and posaconazole with MICs ranging from 3-8 µg/ml. All fungal strains showed 100% resistance to caspofungin, fluconazole and flucytosine with both the methods, and 100% resistance to micafungin and anidulafungin in the gradient strip method.
PubMed: 35068614
DOI: 10.1007/s12088-021-00966-y -
Oral Surgery, Oral Medicine, Oral... Nov 2020Oral candidiasis is a common opportunistic infection that requires knowledge of the various clinical presentations and management strategies for successful treatment.... (Review)
Review
Oral candidiasis is a common opportunistic infection that requires knowledge of the various clinical presentations and management strategies for successful treatment. Numerous local and systemic factors contribute to the development of candidiasis, and the infections can range from superficial mucocutaneous overgrowths to invasive bloodstream infections with a high mortality rate. In addition to Candida albicans, various fungal strains have been isolated from the oral cavity, including C. tropicalis, C. glabrata, C. krusei, and many others. Antifungal agents are available in various forms, each with differing indications, dosing regimens, adverse effects, and drug interactions. Some antifungal agents are available as oral suspensions, pastilles, or creams, whereas others are administered systemically in capsule or intravenous form. This review describes the various presentations of oral candidiasis and the diagnostic methods and treatment alternatives, with a specific focus on pharmacologic management. Spectra of activity, mechanisms of action, adverse reactions, drug interactions, and dosing regimens are explored in the context of both topical and systemic pharmacotherapy used to treat candidiasis. Polyenes (nystatin, amphotericin B); azoles (ketoconazole, miconazole, clotrimazole, fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole); and echinocandins (caspofungin, micafungin, anidulafungin) are discussed. Novel approaches in antifungal therapy with the use of probiotics are also reviewed.
Topics: Amphotericin B; Antifungal Agents; Dentistry; Drug Resistance, Fungal; Echinocandins; Fluconazole; Microbial Sensitivity Tests
PubMed: 32907786
DOI: 10.1016/j.oooo.2020.08.011 -
Antimicrobial Agents and Chemotherapy Mar 2018We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat We also determine the...
We report the mutant prevention concentration (MPC) and mutant selection window (MSW) for micafungin and anidulafungin administered to treat We also determine the mutation frequency. We studied 20 echinocandin-susceptible, fluconazole-intermediate, and wild-type isolates. Adjusted inocula were stroked directly onto Sabouraud agar plates containing different concentrations of micafungin or anidulafungin and visually inspected daily for up to 5 days of incubation. Individual colonies growing on the plates containing echinocandins at 1 mg/liter were selected for antifungal susceptibility testing. The genes of the resulting individual phenotypically resistant colonies were sequenced, and the MPC, MSW, and mutation frequency were determined. Biofilm was quantified, and the growth kinetics and virulence ( model) of the resulting individual mutant colonies were studied. For micafungin and anidulafungin, we found similar results for the MPC (0.06 to 2 mg/liter and 0.25 to 2 mg/liter, respectively), MSW (0.015 to 2 mg/liter for both echinocandins), and mutation frequency (3.7 × 10 and 2.8 × 10, respectively). A total of 12 isolates were able to grow at 1 mg/liter on echinocandin-containing plates, yielding a total of 32 phenotypically resistant colonies; however, mutations (ΔF658, S663P, W715L, and E655A) were observed only in 21 colonies. We did not find differences in biofilm formation, the kinetic parameters studied, or the median survival of larvae infected by wild-type isolates and the resulting individual mutant colonies. Echinocandin concentrations lower than 2 mg/liter can lead to selection of resistance mutations in isolates .
Topics: Anidulafungin; Antifungal Agents; Candida glabrata; Drug Resistance, Fungal; Echinocandins; Humans; Micafungin; Mutation
PubMed: 29311063
DOI: 10.1128/AAC.01982-17