scholarly journals Immunopathogenesis of Emerging Candida auris and Candida haemulonii Strains

2021 ◽  
Vol 7 (9) ◽  
pp. 725
Author(s):  
Sujiraphong Pharkjaksu ◽  
Nawarat Boonmee ◽  
Chalermchai Mitrpant ◽  
Popchai Ngamskulrungroj
Keyword(s):  
Candida Species ◽  
Antifungal Susceptibility ◽  
Case Fatality ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Zebrafish Model ◽  
Minimal Inhibitory Concentrations ◽  
In Vitro Antifungal Susceptibility ◽  
Almost All

The emergence of a multidrug-resistant Candida species, C. auris and C. haemulonii, has been reported worldwide. In Thailand, information on them is limited. We collected clinical isolates from Thai patients with invasive candidiasis. Both species were compared with a laboratory C. albicans strain. In vitro antifungal susceptibility and thermotolerance, and pathogenesis in the zebrafish model of infection were investigated. Both species demonstrated high minimal inhibitory concentrations to fluconazole and amphotericin B. Only C. auris tolerated high temperatures, like C. albicans. In a zebrafish swim-bladder-inoculation model, the C. auris-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of C. auris, C. haemulonii, and C. albicans were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging Candida species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for C. auris infections. Almost all immune response genes to C. auris had a peak response at an early infection time, which contrasted with C. haemulonii. In conclusion, both emerging species were virulent in a zebrafish model of infection and could activate the inflammatory pathway. This study serves as a stepping stone for further pathogenesis studies of these important emerging species.

scholarly journals Indifferent effect of nonsteroidal anti-inflammatory drugs (NSAIDs) combined with fluconazole against multidrug-resistant Candida auris

2019 ◽  
Author(s):  
Fatemeh Ahangarkani ◽  
Sadegh Khodavaisy ◽  
Shahram Mahmoudi ◽  
Tahereh Shokohi ◽  
Mohammad Sadegh Rezai ◽  
...  
Keyword(s):  
Candida Species ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Mortality And Morbidity ◽  
Antifungal Drug Resistance ◽  
Fluconazole Resistant ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Almost All

Background and Purpose: Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination. Materials and Methods: The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis. Results: The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 µg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log2 dilutions. Conclusion: Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted.

scholarly journals Molecular Identification and Antifungal Susceptibility Patterns of Candida Species Isolated from Candidemia Patients in Yasuj, Southwestern Iran

2021 ◽  
Vol 14 (7) ◽  
Author(s):  
Shaghayegh Rostami Yasuj ◽  
Maral Gharaghani ◽  
Seyed Sajjad Khoramrooz ◽  
Marjan Salahi ◽  
Ali Keshtkari ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Amphotericin B ◽  
Molecular Identification ◽  
Candida Species ◽  
Antifungal Susceptibility ◽  
Hospitalized Patients ◽  
Susceptibility Tests ◽  
In Vitro Antifungal Susceptibility ◽  
Susceptibility Patterns

Background: Candidemia is the most common systemic infection in hospitalized patients causing high mortality. Hence, the diagnosis of this infection in the early stage with appropriate antifungal therapy is paramount. Objectives: The study aimed at molecular identification of Candida species isolated from candidemia patients and evaluation of the in vitro antifungal susceptibility patterns of these strains to fluconazole, amphotericin B, and caspofungin. Methods: In the present study, 800 hospitalized patients who were suspected to have candidemia were sampled. Candida species were isolated and identified based on morphological characteristics and PCR-sequencing of the ITS1-5.8S-ITS2 region. Antifungal susceptibility tests for fluconazole, amphotericin B, and caspofungin were performed according to the Clinical and Laboratory Standards Institute protocol M27-A3. Also, clinical data were recorded from the patients' records. Results: Twenty-seven patients among the sample of hospitalized patients were found to have candidemia. A total of 33.3% of candidemia patients were treated with amphotericin B, in which case the mortality rate was 14.8%. The majority of patients (59%) were from the neonatal intensive care unit, and premature birth was the most common underlying condition. Candida albicans (n = 18; 66.6%) was the most common species isolated from blood cultures, followed by C. parapsilosis (n = 7; 25.9%), C. pelliculosa (n = 1; 3.7%), and C. tropicalis (n = 1; 3.7%). Only one C. albicans isolate resistant to fluconazole (minimum inhibitory concentration = 32 µg/mL). Conclusions: Generally, C. albicans has been the most frequent causative agent of candidemia. Resistance to antifungal drugs among candidemia agents was rare. Also, the identification of Candida isolates at the species level with in vitro antifungal susceptibility tests helps manage candidemia patients better and decrease the mortality rate among them.

scholarly journals In Vitro Interactions of Echinocandins with Triazoles Against Multidrug-Resistant Candida auris

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S82-S82
Author(s):  
Hamid Badalii
Keyword(s):  
Amphotericin B ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
In Vivo Studies ◽  
Synergistic Activity ◽  
Candida Auris ◽  
Unsuccessful Treatment ◽  
In Vitro Interactions

Abstract Background Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia. Methods The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique. Results Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments. Conclusion In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended. Disclosures All authors: No reported disclosures.

scholarly journals Antifungal Susceptibility In Vitro Determined by the Etest(r) for Candida Obtained from the Oral Cavity of Irradiated and Elderly Individuals

2015 ◽  
Vol 26 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Edimilson Martins de Freitas ◽  
Larissa Cavalcanti Monteiro ◽  
Michelle Bonfim da Silva Fernandes ◽  
Hercílio Martelli Junior ◽  
Paulo Rogério Ferreti Bonan ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Candida Species ◽  
Antifungal Susceptibility ◽  
Culture Collection ◽  
Morphological Criteria ◽  
Group 2 ◽  
In Vitro Antifungal Susceptibility ◽  
Mic Minimum Inhibitory Concentration ◽  
Dose Dependent

This study aimed to evaluate the in vitro antifungal susceptibility of Candida species of head-and-neck-irradiated patients (Group 1), non-institutionalized (Group 2) and institutionalized elders (Group 3) using Etest(r) methodology. Candida was isolated from saliva and presumptively identified by CHROMagar Candida(r), confirmed by morphological criteria, carbohydrate assimilation (API 20C AUX(r)) and genetic typing (OPE 18). The collection was made from 29, 34 and 29 individuals (Groups 1, 2 and 3, respectively) with 67 isolates. Etest(r) strips (ketoconazole, itraconazole, fluconazole, amphotericin B and flucytosine) on RPMI (Roswell Park Memorial Institute) agar, on duplicate, were used to evaluate susceptibility. ATTC (American Type Culture Collection) 10231 (Candida albicans) was used as quality control. Among the 67 isolates of Candida species, most were susceptible to azoles, flucytosine and amphotericin B. None of the isolates showed resistance and dose-dependent susceptibility to amphotericin B. There were nine strains resistant to itraconazole, six to fluconazole and two to ketoconazole and ten dose-dependent, mainly to flucytocine. The highest MIC (minimum inhibitory concentration) to C. albicans, C. tropicalis, C. parapsilosis was 2.671 μg.mL-1, 8.104 μg.mL-1, 4.429 μg.mL-1, all for flucytosine. C. krusei and C. glabrata were associated with higher MIC for azoles and C. glabrata with higher MIC to flucytosine. In summary, susceptibility to all tested antifungal agents was evident. The isolates were more resistant to itraconazole and dose-dependent to flucytosine. A comparison of C. albicans in the three groups showed no outliers. Higher MIC was associated with C. krusei and C. glabrata.

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