Epidemiology and molecular mechanisms of antifungal resistance in <i>Candida</i> and <i>Aspergillus</i>

Gonçalves, Sarah Santos; Souza, Ana Carolina Remondi; Chowdhary, Anuradha; Meis, Jacques F.; Colombo, Arnaldo Lopes

doi:10.1111/myc.12469

Cited by 162 publications

(130 citation statements)

References 331 publications

(439 reference statements)

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“…5 Antibiotic resistance has been identified as a global health threat and efforts from governmental and non-governmental agencies have been directed towards facing this challenge through rationalization of antibiotic use. However, much less is known about the prevalence and mechanisms of antifungal drug resistance and the subsequent clinical and economic consequences.…”

Section: Introductionmentioning

confidence: 99%

Bibliometric analysis of literature on antifungal triazole resistance: 1980 – 2015

Sweileh

Sawalha

Al-Jabi

et al. 2017

GERMS

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Background Triazole antifungal agents play an important role in the treatment of a wide range of fungal infections. Little is known about antifungal triazole drug resistance when compared to antibiotic resistance. Therefore, this study was carried out to give a bibliometric overview of literature on triazole antifungal drug resistance.Methods Keywords related to triazole drug class and resistance were used in a search query in the Scopus search engine. The time span was set from 1980 to 2015. Data pertaining to growth of publications, the most active countries and institutions, the most cited articles, and mapping of molecular mechanisms of resistance were analyzed.Results A total of 1648 journal articles were retrieved with an average of 20.46 citations per article. Annual growth of triazole resistance showed an increasing pattern during the study period. The United States of America (n=446; 27.06%) ranked first in productivity followed by the United Kingdom (UK) (n=176; 10.68%), and China (n=133; 8.07%). Radboud University Nijmegen Medical Centre (n=69, 4.19%) in the Netherlands ranked first in productivity, while the journal Antimicrobial Agents and Chemotherapy ranked first (n=255; 15.47%) in publishing articles on triazole resistance. Mapping mechanisms of resistance showed that efflux pump and mutations in target enzyme are major mechanisms described in resistance to triazoles.Conclusion There was a growth of publications on triazole resistance in the past two decades with the bulk of publications on triazole resistance in Candida species. The data presented here will serve as baseline information for future comparative purposes.

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Section: Introductionmentioning

confidence: 99%

Bibliometric analysis of literature on antifungal triazole resistance: 1980 – 2015

Sweileh

Sawalha

Al-Jabi

et al. 2017

GERMS

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“…In recent years, however, fluconazole-resistant species, such as Candida krusei and Candida glabrata, have been isolated with increasing frequency (9,10). This is cause for concern (11)(12)(13), and recent reports have found that approximately 7% of all Candida bloodstream isolates tested were fluconazole resistant (14). Furthermore, the frequency of resistance among these strains appears to be increasing.…”

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confidence: 99%

A Risk Score for Fluconazole Failure among Patients with Candidemia

Ostrosky-Zeichner¹,

Harrington

Azie

et al. 2017

Antimicrob Agents Chemother

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This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positive Candida culture Ն10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics, Candida species, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow test P value of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.

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“…The common use of azole antifungal agents, in particular oral fluconazole, but also topical azoles, for the treatment of cutaneous and oral candidiasis, and possibly due to the use of azole fungicides in agricultural crop protection, has led to the emergence of azole and echinocandine resistance of clinical isolates of Candida (C.) albicans and other Candida species [1]. An alternative therapeutic approach is the use of topical polyene antifungals such as amphotericin B or nystatin.…”

Section: Introductionmentioning

confidence: 99%

In vitro susceptibility testing of yeasts to nystatin – low minimum inhibitory concentrations suggest no indication of in vitro resistance of Candida albicans, Candida species or non-Candida yeast species to nystatin

Nenoff¹,

Krüger²,

Neumeister³

et al. 2016

Clin Med Invest

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In total, 14 yeast strains originating from patients with dermatomycoses, and 7 control strains (isolates from strain collections and collaborative ring trials) were investigated regarding their in vitro susceptibility to the polyene antifungal agent nystatin. Testing was performed using a broth microdilution assay based on the standardized method of susceptibility testing of yeasts per EUCAST (The European Committee on Antimicrobial Susceptibility Testing). Minimum inhibitory concentrations (MIC) for nystatin were measured. The reading of the MIC values was performed by both visual examination, and spectrophotometric measuring after 24 and 48 hours' incubation time at 36°C.The visual read-out of growth inhibition revealed MICs for nystatin in a range from 3.7 to 7.4 IU/mL (0.625 to 1.25 µg/mL) for all Candida species tested. One of the Candida (C.) albicans strains, and both strains of C. glabrata and C. tropicalis, showed low MIC values of 3.7 IU/mL (0.625 µg/mL). Geotrichum candidum and Trichosporon mucoides were also inhibited by nystatin. The control strains (C. albicans, C. glabrata, C. parapsilosis, C. krusei and C. tropicalis) confirmed the values which were found for the wild strains. The spectrophotometric measuring of the turbidimetry revealed slightly lower MIC values for Candida species. Spectrophotometric measurment of Geotrichum candidum and Trichosporon mucoides was unsuccessful or not possible; however, visual reading of the results was carried out effectively. Nystatin showed very good in vitro activity against these non-Candida yeast species. In conclusion, very good in vitro activity of nystatin against all tested yeast strains could be detected. The in vitro efficacy was independent of the origin of the strains, as both the wild strains isolated from patients in this study, and the control strains originating from strain collections, were inhibited. IntroductionThe common use of azole antifungal agents, in particular oral fluconazole, but also topical azoles, for the treatment of cutaneous and oral candidiasis, and possibly due to the use of azole fungicides in agricultural crop protection, has led to the emergence of azole and echinocandine resistance of clinical isolates of Candida (C.) albicans and other Candida species [1]. An alternative therapeutic approach is the use of topical polyene antifungals such as amphotericin B or nystatin. Only limited current data exists regarding Candida species which are resistant to polyene antifungals. Recently, a total of 201 clinical C. albicans isolates from Turkey investigated by Etest were found to be susceptible to amphotericin B [2]. A similar situation can be found for nystatin. However, in vitro susceptibility testing studies have shown a low percentage of Candida species isolated from HIV positive patients to be resistant to nystatin [3].In this study, a total of 14 currently isolated yeast strains from dermatomycosis patients, and seven reference strains (controls), including isolates from the DSMZ strain collection (German Collectio...

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Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus

Cited by 162 publications

References 331 publications

Bibliometric analysis of literature on antifungal triazole resistance: 1980 – 2015

Bibliometric analysis of literature on antifungal triazole resistance: 1980 – 2015

A Risk Score for Fluconazole Failure among Patients with Candidemia

In vitro susceptibility testing of yeasts to nystatin – low minimum inhibitory concentrations suggest no indication of in vitro resistance of Candida albicans, Candida species or non-Candida yeast species to nystatin

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