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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 10185

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Dr. Stefanie Bressan Waller

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Department of Clinical Pathology, Veterinary Mycology Section, Faculty of Veterinary Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
Interests: public health; veterinary mycology; zoonosis; sporotrichosis; antifungal therapy; antifungal resistance; natural products; antimicrobial susceptibility testing

Special Issue Information

Dear Colleagues,

Fungal infections represent a growing concern in both human and veterinary medicine, affecting a wide range of hosts and resulting in significant morbidity and mortality. The emergence of resistant strains, coupled with the limited number of effective antifungal agents, underscores the urgent need for new diagnostic and therapeutic approaches. This Special Issue aims to bring together high-quality research, case reports, and reviews that address the epidemiology, pathogenesis, diagnosis, and treatment of fungal infections across different species, including humans. We encourage the submission of works that investigate host–pathogen interactions, resistance mechanisms, the discovery of new antifungal drugs, and innovative therapeutic strategies, such as natural products, drug combinations, and nanotechnology-based systems. Contributions that integrate findings between human and animal health, from a One Health perspective, are particularly welcome. By integrating clinical, laboratory, and field data, this Special Issue seeks to foster a comprehensive understanding of fungal diseases and promote the development of more effective antifungal interventions.

Dr. Stefanie Bressan Waller
Guest Editor

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Keywords

fungal infections
antifungal agents
antifungal drug discovery

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Published Papers (9 papers)

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Research

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18 pages, 3667 KB

Open AccessArticle

Potential Antifungal Activity of Retinoids Against Non-albicans Candida Species

by Terenzio Cosio, Enrico Salvatore Pistoia, Francesca Pica, Augusto Orlandi, Elena Campione and Roberta Gaziano

Microorganisms 2026, 14(4), 759; https://doi.org/10.3390/microorganisms14040759 - 27 Mar 2026

Viewed by 485

Abstract

Non-albicans Candida (NAC) species have emerged as significant opportunistic pathogens due to their reduced susceptibility to antifungal agents combined with their strong ability to form biofilms. The severity of systemic candidiasis caused by NAC species highlights the need for novel antifungal strategies. Retinoids, a group of compounds derived from vitamin A, have been demonstrated to possess significant antifungal activity against the reference strain C. albicans ATCC 2091. This study aimed to assess the antifungal potential of three retinoids, all-trans retinoic acid (ATRA), trifarotene, and tazarotene, against NAC clinical isolates. Various concentrations of the retinoids (from 1 mM to 0.06 mM) were tested in vitro against the growth, adhesion, and biofilm development of NAC species, including Candida glabrata, Candida krusei, and Candida tropicalis, as well as a reference strain of C. auris (CDC B11903). At 1 mM, all three compounds maximally inhibited the growth, adhesion, and biofilm formation of all tested NAC species. At lower concentrations (0.5–0.06 mM), C. krusei remained the most susceptible, especially to tazarotene. Tazarotene also showed a strong inhibitory effect on C. auris and C. glabrata at 0.5–0.25 mM; however, this effect was weaker than that observed against C. krusei. At low concentrations (0.12–0.06 mM), only trifarotene induced a mild but statistically significant inhibition of C. tropicalis growth. Trifarotene at 0.5 mM was also the most effective retinoid in inhibiting C. glabrata and C. tropicalis adherence and biofilm formation, with inhibitory activity maintained even at sub-0.5 mM concentrations (0.25–0.12 mM). Overall, the results suggest that all three retinoids exhibited dose-dependent and species-specific antifungal activity against NAC species, supporting their potential as novel, tailored antifungal agents against drug-resistant Candida strains. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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11 pages, 223 KB

Open AccessArticle

Incidence and Outcomes of Invasive Aspergillosis in Hospitalized Patients with Pancreatic Transplantation: A Nationwide Population-Based Analysis

by Aditya Sharma, Marc Piper, Rahul Maheshwari and Ayman O. Soubani

Microorganisms 2026, 14(3), 669; https://doi.org/10.3390/microorganisms14030669 - 16 Mar 2026

Viewed by 555

Abstract

Background: Invasive Aspergillosis (IA) is a rare but life-threatening fungal infection in immunocompromised hosts, including solid organ transplant (SOT) recipients. While extensively studied in other SOT populations, data on IA in pancreas transplant (PT) recipients are limited. Earlier studies reported mortality rates nearing 100%, whereas more recent data show that 12-week mortality still exceeds 20% despite improvements in antifungal therapy. Current prophylaxis strategies for PT recipients mainly focus on Candida species, and there are no clear, standardized recommendations for Aspergillus prevention. Given the paucity of focused data, the epidemiology, clinical characteristics, and outcomes of IA in PT recipients are not well defined. This study aimed to assess the incidence, clinical characteristics, and outcomes of IA among hospitalized PT patients using a nationally representative dataset. Methods: We conducted a descriptive analysis using the National Inpatient Sample (NIS) from 2016 to 2020. PT admissions were identified using International Classification of Diseases, Tenth Revision (ICD 10) codes for transplant status and procedures. IA was defined using validated ICD 10 codes. Baseline demographics, hospital characteristics, comorbidities, and outcomes, including sepsis, acute kidney injury (AKI), acute respiratory failure (ARF), invasive mechanical ventilation (IMV), all-cause in-hospital mortality, length of stay, and total hospitalization costs and charges were compared between PT admissions with and without IA. National estimates were calculated using discharge weights, and comparisons were performed using the chi-square test and adjusted Wald test. Multivariable analysis was performed to identify predictors of all-cause in-hospital mortality among PT admissions complicated by IA. Two-sided p values < 0.05 were considered statistically significant. Results: Between 2016 and 2020, 65,980 PT-related hospitalizations were identified, of which 250 (0.4%) had IA. PT admissions complicated by IA were more commonly aged 41 to 60 years (59% vs. 46%, p = 0.012) and were less likely to have a Charlson Comorbidity Index greater than 3 (54% vs. 68.6%, p < 0.001) compared with PT hospitalizations without IA. The PT with the IA cohort had higher rates of sepsis (100% vs. 46.1%, p < 0.001), AKI (60% vs. 36.7%, p < 0.001), ARF (28% vs. 9.4%, p < 0.001), and IMV use (18% vs. 4%, p < 0.001) compared with the PT without the IA cohort. Among PT hospitalizations with IA, IMV use was independently associated with higher all-cause in-hospital mortality (adjusted odds ratio 48.777, p = 0.009). Overall, in-hospital mortality was significantly higher in PT hospitalizations with IA compared with those without IA (12% vs. 2%, p < 0.001). Mean length of stay was longer (24.86 vs. 6.13 days, p < 0.001), and total charges ($378,494 vs. $94,938, p < 0.001), and total costs ($93,019 vs. $24,463, p = 0.023) were significantly higher compared with PT hospitalizations without IA. Conclusion: Although rare, IA in PT recipients is associated with higher rates of sepsis, AKI, ARF, venous thromboembolism, prolonged hospitalization, increased mortality, and greater healthcare utilization. Despite the inherent limitations of administrative datasets, this nationally representative analysis highlights the substantial clinical and economic burden of IA in this high-risk population. These findings emphasize the need for targeted surveillance, early diagnosis, and evidence-based antifungal strategies in this vulnerable population. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

12 pages, 645 KB

Open AccessArticle

Clinical Manifestations, Antifungal Susceptibilities, and Outcome of Ocular Infections Caused by Purpureocillium lilacinum

by Xinlei Zhao, Jinliang Jiang, Huijing Huang, Jiayi Zheng, Liuxueying Zhong and Fang Duan

Microorganisms 2025, 13(12), 2858; https://doi.org/10.3390/microorganisms13122858 - 16 Dec 2025

Cited by 1 | Viewed by 629

Abstract

Purpureocillium lilacinum is an emerging pathogen that can cause severe ocular infections. This study aimed to investigate the risk factors, clinical manifestations, antifungal susceptibilities, and outcomes of ocular infections caused by P. lilacinum at a large ophthalmic center in Southern China. This retrospective study reviewed the medical records of 34 patients with culture-proven P. lilacinum oculomycosis treated at the Zhongshan Ophthalmic Center from January 2020 to December 2024. The study included 34 patients (17 males, 17 females). The most common risk factor was ocular trauma (38.2%). In vitro susceptibility testing revealed high resistance to fluconazole and caspofungin, but general susceptibility to voriconazole (median MIC 0.25 mg/L). Despite 97.1% of patients receiving voriconazole therapy, outcomes were generally poor, with 54.5% of patients experiencing a poor outcome (vision worse than counting fingers). A significantly shorter time to microbiological diagnosis was associated with a favorable outcome (median 26 days vs. 65 days, p = 0.007). In conclusion, the visual outcomes of this infection remain generally poor, with the major clinical challenge being the delay in diagnosis. Therefore, prompt microbiological investigation is recommended for patients with suspected intraocular infection. Voriconazole remains the first-line therapeutic choice, the therapeutic potential of newer triazoles warrants further investigation. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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12 pages, 604 KB

Open AccessCommunication

Antifungal Efficacy of Selected Plant Essential Oils Against Clinical Canine Isolates Malassezia pachydermatis

by Eva Čonková, Peter Váczi and Zuzana Malinovská

Microorganisms 2025, 13(12), 2675; https://doi.org/10.3390/microorganisms13122675 - 24 Nov 2025

Viewed by 1681

Abstract

Malassezia pachydermatis, an important opportunistic secondary pathogen, is often associated with atopic dermatitis or otitis externa in dogs. Recent studies indicate an increase in resistance of this yeast to commonly used antifungal agents. Therefore, the search for new antifungal agents is a challenge. In the present study, the susceptibility of M. pachydermatis strains to 10 plant essential oils—EOs (bergamot, grapefruit, coriander, hyssop, lavender, tea tree, nutmeg, oregano, rosemary, and Spanish sage) was determined using the broth microdilution method. All 15 clinical strains tested were susceptible to coriander (100%). A good antifungal activity was shown for EO from nutmeg (93.33%), bergamot (86.66), Spanish sage and hyssop (73.33%) and rosemary (66.67%). Lower antifungal efficacy was identified in EOs from grapefruit, lavender, tea tree and oregano (53.33%). The obtained results indicate promising prospects for the clinical use of essential oils in the treatment of M. pachydermatis infections. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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16 pages, 8828 KB

Open AccessArticle

Fatal Pneumonia Caused by Beauveria bassiana in a Kemp’s Ridley Sea Turtle (Lepidochelys kempii, Garman, 1880) on the Portuguese Coast: Case Report and Review of Beauveria spp. Infections in Reptiles

by Gonçalo N. Marques, Ricardo Lopes, Maria Conceição Peleteiro, Jaqueline T. Bento, João R. Mesquita, Fábio Abade dos Santos, Leonor Delgado, Ana Cláudia Coelho, Miguel Lourenço, Miriam Leal, Virgínia Lopes, Ana Paula Castro, Rita Barny, Joana Guerra, Nuno Urbani, Antonieta Nunes, Yohann Santos, Isabel Gaspar, Andreia Garcês and João Neves

Microorganisms 2025, 13(9), 2092; https://doi.org/10.3390/microorganisms13092092 - 8 Sep 2025

Viewed by 2485

Abstract

The Kemp’s ridley sea turtle (Lepidochelys kempii) is the most critically endangered sea turtle species, with a distribution primarily restricted to the Gulf of Mexico. Its occurrence along the Iberian Peninsula is exceedingly rare. This study describes the postmortem findings of a juvenile L. kempii rescued off the Portuguese coast in 2024, which died after 11 days in rehabilitation despite intensive supportive care. Necropsy revealed severe, diffuse pneumonia. Histopathological examination showed interstitial inflammation and branching septate hyphae, while fungal culture and DNA sequencing confirmed the presence of Beauveria bassiana. Mycotic diseases in reptiles are often underrecognised but can lead to significant morbidity and mortality, particularly in immunocompromised or stressed individuals such as stranded marine turtles. This rare occurrence of a L. kempii on the Portuguese coast provides important insights into the species’ dispersal patterns and underlines the potential conservation implications of opportunistic fungal infections in endangered species. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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13 pages, 1819 KB

Open AccessArticle

Human-like Biofilm Models to Study the Activity of Antifungals Against Aspergillus fumigatus

by Dan-Tiberiu Furnica, Julia Falkenstein, Silke Dittmer, Joerg Steinmann, Peter-Michael Rath and Lisa Kirchhoff

Microorganisms 2025, 13(9), 2040; https://doi.org/10.3390/microorganisms13092040 - 31 Aug 2025

Viewed by 1572

Abstract

Aspergillus fumigatus is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host’s immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by A. fumigatus increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against A. fumigatus. In both assays, metabolically active A. fumigatus biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against Aspergillus biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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Review

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20 pages, 1078 KB

Open AccessReview

Managing Breakthrough Fungal Infections in Hematologic Patients: Determinants and Practical Management from a Latin American Perspective on Behalf of INFOCUS LATAM–ISHAM Working Group

by Larissa Simão Gandolpho, Daniel Aguilar-Zapata, Pablo Andrés Moncada-Vallejo, Fernando Riera, Mariana Guaraná, Giovanni Luis Breda, Ricardo Rabagliati, Marcio Nucci and Arnaldo Lopes Colombo

Microorganisms 2026, 14(4), 904; https://doi.org/10.3390/microorganisms14040904 - 16 Apr 2026

Viewed by 414

Abstract

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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19 pages, 777 KB

Open AccessReview

Nanodrugs for Subcutaneous Mycoses: Applications, Antifungal Performance, and Translational Perspectives

by Micaela Federizzi, Eduarda Canosa Adegas, Alexandre Meneghello Fuentefria and Stefanie Bressan Waller

Microorganisms 2026, 14(1), 187; https://doi.org/10.3390/microorganisms14010187 - 14 Jan 2026

Viewed by 552

Abstract

Subcutaneous mycoses are a heterogeneous group of chronic fungal infections, usually acquired through traumatic inoculation of environmental fungi and particularly severe in immunocompromised and critically ill patients. These infections involve pathogens with marked morphological and physiopathological diversity, resulting in significant diagnostic and therapeutic challenges. Conventional treatment relies on systemic antifungals such as amphotericin B, itraconazole, and other azoles; however, these therapies are often limited by poor tissue penetration, adverse effects, and prolonged treatment regimens, especially in vulnerable patient populations. In this context, nanodrugs have emerged as promising alternatives by improving solubility, stability, bioavailability, and targeted delivery to infection sites. This review conducted a comprehensive literature search in PubMed, SciELO, ScienceDirect, Web of Science, and Scopus, identifying 31 eligible studies that developed and evaluated antifungal nanosystems using in vitro, ex vivo, and/or in vivo models. Quantitative outcomes included minimum inhibitory concentration (MIC), colony-forming units (CFU), inhibition halo diameter, and survival assays. Overall, the evidence indicates that several nanosystems may overcome key pharmacological limitations of conventional antifungals and enhance therapeutic outcomes. Nevertheless, important translational challenges remain, including toxicity, long-term safety, scalability, and regulatory approval, which must be addressed before clinical implementation. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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Other

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16 pages, 698 KB

Open AccessSystematic Review

Treatment Options and Antifungal Resistance in Pediatric Candidozyma auris (Previously Candida auris) Infections: A Systematic Review of Clinical Outcomes

by Konstantinos Stergiou, Kanellos Skourtsidis, Georgios Kiosis, Despoina Ioannou, Vasilis-Spyridon Tseriotis, Vasileios Fouskas, Sofia Karachrysafi, Elias Iosifidis, Emmanuel Roilides, Theodora Papamitsou and Maria Kourti

Microorganisms 2026, 14(1), 228; https://doi.org/10.3390/microorganisms14010228 - 19 Jan 2026

Cited by 1 | Viewed by 962

Abstract

Candidozyma auris (previously named Candida auris) has been recognized as a significant public health threat due to its extensive transmission in hospital settings, high mortality rates, and multidrug resistance. Evidence regarding optimal antifungal treatment in children remains limited. The present systematic review aims to synthesize available evidence on pediatric C. auris infections, focusing on antifungal treatment, resistance profiles, and clinical outcomes. A systematic search was conducted across PubMed, Scopus, and Web of Science, identifying case reports and case series of pediatric patients with confirmed C. auris infection. Data were extracted on demographics, comorbidities, infection site, antifungal therapy, and outcomes. Risk of bias was assessed using JBI Critical Appraisal checklists. Fourteen studies comprising 62 patients were included, with most cases being bloodstream infections. C. auris showed widespread fluconazole resistance and variable susceptibility to amphotericin B. Echinocandins were the most commonly used agents, generally associated with survival. Overall mortality was 35%, similar to that reported for adults. Combination therapy showed numerically higher survival, although given the small sample size and heterogeneity of treatment regimens, no comparative inferences can be made. Pediatric C. auris infections mirror adult patterns of antifungal resistance and mortality. Echinocandins remain first line therapy; however, the emergence of echinocandin resistance underscores the urgent need for antifungal stewardship, standardized pediatric guidelines, and novel antifungal development. Full article

(This article belongs to the Special Issue Fungal Infections and Antifungal Agents)

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