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Pathogens
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Antifungal Resistance in Pathogenic Fungi
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Antifungal Resistance in Pathogenic Fungi

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 3450

Special Issue Editors

Dr. Ana V. Espinel-Ingroff

E-Mail Website
Guest Editor
Virginia Commonwealth University Medical Center, Richmond, VA, USA
Interests: antifungal susceptibility testing and development of ECVs for fungal species; antifungal resistance; medical mycology; epidemiology
Special Issues, Collections and Topics in MDPI journals
Dr. Eric Dannaoui

E-Mail Website
Guest Editor
1. Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, F-75015 Paris, France
2. Faculté de Médecine, Université Paris Cité, F-75006 Paris, France
Interests: human pathogenic fungi; antifungals; mycoses; Aspergillus; in vitro susceptibility testing; antifungal resistance; animal models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The topic is antifungal resistance. There are different ways in which antifungal resistance could be interpreted, evaluated, and discussed: 1) fungal epidemiology; 2) innate or acquired resistance among emerging species (C. auris, C. haemulonii, C. pseudohaemulonii, etc.); 3) antifungal resistance mechanisms, including those for the new agents (e.g., Candida spp., Aspergillus spp., Cryptococcus spp.); and 4) clinical resistance. Reference (CLSI, EUCAST) and commercial (Sensititre YeastOne and bioMérieux Etest) methods have been developed for susceptibility testing. In the absence of clinical data, ECVs (ECOFFs) are available for certain species/agent/method combinations. These ECVs are based on in vitro data and can identify mutants (non-wild type), but not resistant isolates (non-responsive to therapy), as clinical breakpoints (BPs). Other important factors in patient care are the pharmacokinetics/pharmacodynamics (PK/PD) of each agent and species, e.g., the significant inter- and intra-patient triazole variability, which can alter treatment outcome and/or lead to drug toxicity. These issues, as well as resistance detection, will be reviewed for the listed fungal groups below:

a) The Candida, focusing on the less common strains and/or innately resistant to established/new agents.
b) The Cryptococcus species complex (a problem among HIV-positive patients), inherently resistant to the echinocandins associated with the upregulation of the ERG11 gene, efflux pumps and others.
c) A terreus and other less common species, innately resistant to amphotericin B and other agents.
d) Mucorales infections are usually treated with high-dose liposomal amphotericin B, intravenous, delayed-release posaconazole tablets (such as isavuconazole), and new therapeutic strategies. The Mucorales species (incorrectly defined as “the black fungi”) epidemic observed among COVID-19 patients suffering from additional pulmonary infections caused by these species is another important topic.  
e) Scedosporium apiospermum complex isolates are mostly resistant to amphotericin B (break through infections). Voriconazole is the drug of choice, but what is the role of these new agents (e.g., fosmanogepix (APX001 and others)?
f) What is the role of BPs or ECVs for the Sporothrix species?
Dermatophytes, where terbinafine resistance has been documented among T. rubrum and T. mentagrophytes, can also be evaluated.

You are invited to submit articles for this Special Issue (SI), which can include original research articles and reviews focused on all aspects of antifungal resistance, such as epidemiology, mechanisms of resistance, technical issues, and new therapeutic options to fight resistance.

Dr. Ana V. Espinel-Ingroff
Dr. Eric Dannaoui
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antifungal resistance
  • breakpoints for antifungal testing
  • reference BPs for moulds and yeasts
  • reference and commercial ECVs for yeasts and moulds
  • methods for fungal mutant detection
  • Candida
  • Aspergillus
  • Dermatophytes

Published Papers (2 papers)

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Research

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15 pages, 1750 KiB  
Article
Species Distribution and Antifungal Susceptibilities of Aspergillus Section Terrei Isolates in Clinical Samples from the United States and Description of Aspergillus pseudoalabamensis sp. nov.
by Connie F. Cañete-Gibas, Hoja P. Patterson, Carmita J. Sanders, James Mele, Hongxin Fan, Marjorie David and Nathan P. Wiederhold
Pathogens 2023, 12(4), 579; https://doi.org/10.3390/pathogens12040579 - 11 Apr 2023
Cited by 2 | Viewed by 1614
Abstract
Aspergillus section Terrei consists of numerous cryptic species in addition to A. terreus sensu stricto. The treatment of invasive infections caused by these fungi may pose a unique challenge prior to diagnosis and species identification, in that they are often clinically resistant [...] Read more.
Aspergillus section Terrei consists of numerous cryptic species in addition to A. terreus sensu stricto. The treatment of invasive infections caused by these fungi may pose a unique challenge prior to diagnosis and species identification, in that they are often clinically resistant to amphotericin B, with poor outcomes and low survival rates in patients treated with this polyene. Data on the species distributions and susceptibility profiles of isolates within section Terrei from the United States (U.S.) are limited. Here, we report the species distributions and susceptibility profiles for amphotericin B, isavuconazole, itraconazole, posaconazole, voriconazole, and micafungin against 278 clinical isolates of this section from institutions across the U.S. collected over a 52-month period. Species identification was performed by DNA sequence analysis and phenotypic characterization. Susceptibility testing was performed using the CLSI broth microdilution method. The majority of isolates were identified as Aspergillus terreus sensu stricto (69.8%), although several other cryptic species were also identified. Most were cultured from specimens collected from the respiratory tract. Posaconazole demonstrated the most potent activity of the azoles (MIC range ≤ 0.03–1 mg/L), followed by itraconazole (≤0.03–2 mg/L), voriconazole, and isavuconazole (0.125–8 mg/L for each). Amphotericin B demonstrated reduced in vitro susceptibility against this section (MIC range 0.25–8 mg/L), although this appeared to be species-dependent. A new species within this section, A. pseudoalabamensis, is also described. Our results, which are specific to the U.S., are similar to previous surveillance studies of the Aspergillus section Terrei. Full article
(This article belongs to the Special Issue Antifungal Resistance in Pathogenic Fungi)
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16 pages, 367 KiB  
Review
Antifungal Resistance in Cryptococcal Infections
by Marcia S. C. Melhem, Diniz Pereira Leite Júnior, Juliana P. F. Takahashi, Milena Bronze Macioni, Lidiane de Oliveira, Lisandra Siufi de Araújo, Wellington S. Fava, Lucas X. Bonfietti, Anamaria M. M. Paniago, James Venturini and Ana Espinel-Ingroff
Pathogens 2024, 13(2), 128; https://doi.org/10.3390/pathogens13020128 - 29 Jan 2024
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Abstract
Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to [...] Read more.
Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of Cryptococcus neoformans and C. gattii species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and C. neoformans VNI) is available. Full article
(This article belongs to the Special Issue Antifungal Resistance in Pathogenic Fungi)
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