Candidozyma auris (syn. Candida auris) is an emerging multidrug-resistant yeast of growing clinical and environmental concern. Despite its increasing detection in healthcare settings worldwide, environmental evidence remains scarce. This study presents the first molecular detection of C. auris DNA in surface waters of Türkiye, within the Ramsar-protected Gediz Delta, as part of the national One Health Surveillance Framework. A total of 80 surface-water samples were collected from five wetland ecosystems Tuz Lake, Kulu Lake, Göksu Delta (Akgöl and Paradeniz Lagoons), Kızılırmak Delta, and Gediz Delta. Physicochemical parameters; temperature, pH, and salinity were recorded in situ using a multi parameter sensor. Environmental DNA was extracted from 2 L of 0.22 µm Sterivex-filtered water and analyzed via qPCR using C. auris-specific (CauF/CauR) and Candida-genus (CauRelF/CauRelR) primer sets. Yeast isolation was performed on CHROMagar™ Candida Plus, and identification was achieved by MALDI-TOF MS. C. auris DNA was detected in one sample (1.25
Candida auris is an emerging multidrug-resistant yeast demonstrating remarkable persistence in healthcare environments, contributing to nosocomial transmission and outbreak persistence. Increasing disinfectant failure reports have raised concerns regarding infection control policies, as environmental reservoirs play central roles in its spread. We reviewed experimental studies, environmental surveillance reports, and comparative disinfection efficacy data to summarise interactions between C. auris and commonly used biocidal classes: chlorine-based oxidizers, alcohol formulations, biguanides, and quaternary ammonium compounds. Mechanistic findings on biofilm formation, efflux activity, and stress-response pathways were integrated to contextualise tolerance behaviour. Evidence indicates C. auris shows reduced susceptibility to quaternary ammonium compounds and demonstrates variable, strain-dependent tolerance to alcohol-based disinfectants, particularly with organic load or suboptimal contact times. Chlorine-based oxidising agents maintain reliable activity at appropriate concentrations and exposure durations. Biofilm formation enhances environmental persistence and diminishes surface decontamination efficiency. C. auris requires disinfectant strategies distinct from other Candida species. Effective infection prevention depends on optimised agent selection, adequate contact times, and consideration of surface and organic-matter conditions. Tailored decontamination protocols are essential to limit environmental persistence and interrupt nosocomial transmission.
Candida meningitis is a rare but life-threatening infection, most commonly caused by Candida albicans. Candida dubliniensis, despite its close phenotypic similarity to C. albicans, is an uncommon cause of central nervous system (CNS) infections, with limited data available. To date, only 12 cases of C. dubliniensis meningitis have been reported worldwide. This study presents the 13th documented case and the first reported from Türkiye, together with a systematic review of the literature. A 44-year-old immunocompetent male developed meningitis caused by C. dubliniensis following subtotal resection of a clival meningioma. The diagnosis was established through fungal culture, MALDI-TOF MS, and ITS region DNA sequencing. The isolate was deposited in GenBank (accession number PV088619). Antifungal therapy with fluconazole was initiated based on susceptibility results. Despite appropriate antifungal management, the patient developed secondary Klebsiella pneumoniae sepsis and subsequently died, highlighting the complexity and high mortality risk associated with post-neurosurgical fungal CNS infections. A systematic review was conducted according to PRISMA guidelines using PubMed and Web of Science databases, including studies published up to February 2025. Search terms included “Candida dubliniensis” and “meningitis.” Only microbiologically confirmed cases with individual patient data were included. Studies older than 25 years or lacking sufficient diagnostic detail were excluded. Thirteen cases were identified. Most patients were immunocompetent, and infections were frequently acquired outside neurosurgical settings. Mortality was reported in four cases. These findings emphasize the extreme rarity of C. dubliniensis meningitis and underscore the importance of early species-level identification strategies.
Background Candidozyma (Candida) auris is an emerging multidrug-resistant fungal pathogen with expanding ecological presence beyond healthcare settings. Wastewater-based surveillance (WBS) has recently become an important tool for early detection of community-level circulation. However, no environmental monitoring data have previously been reported from Türkiye. This study aimed to investigate the presence of C. auris in hospital-associated wastewater and assess its potential role as an environmental reservoir. Methods Between January and July 2025, 46 wastewater samples were collected twice weekly from the main outlet of a tertiary hospital. Samples underwent concentration, culture on selective chromogenic agar, and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) confirmation. DNA extracted from Sterivex filters was tested using the species-specific CauF/CauR qPCR assay. All runs included appropriate positive, negative, and no-template controls. The Bio-speedy Candida auris Clade Detection qPCR Kit (Bioeksen R&D Technologies Inc., Türkiye) was used for clade identification of the isolates. Antifungal susceptibility testing of the recovered C. auris isolates was performed using the EUCAST reference microdilution method, and minimum inhibitory concentrations (MICs) were interpreted according to EUCAST guidelines. Results C. auris DNA was detected in three wastewater samples (Ct 31–36), and two culture-confirmed isolates were recovered and stored. The repeated qPCR positivity across different sampling dates suggests intermittent yet detectable shedding into the sewage system. Importantly, no outbreak was ongoing in the hospital, with only sporadic clinical cases reported, indicating that even low-level colonization may generate measurable environmental signatures. All isolates were evaluated as Clade-1. Antifungal susceptibility testing revealed high fluconazole MICs (> 64 mg/L) in both C. auris isolates, consistent withno activity of fluconazole. In contrast, low MIC values for echinocandins (anidulafungin 0.06–0.25 mg/L; micafungin 0.125–0.25 mg/L) indicated favorablein vitro activity of this antifungal class against the tested isolates. Conclusion This study provides the first culture-confirmed detection of C. auris in wastewater in a tertiary hospital in Türkiye, demonstrating organism persistence under local wastewater conditions. These findings highlight the value of WBS as an early-warning component of fungal surveillance and underscore the need to integrate environmental monitoring into One Health strategies for C. auris .
In this report a case of cutaneous Scedosporium apiospermum infection in 75-year-old woman with asthma who was receiving long-term therapy with corticosteroids was presented. She was hospitalized in the department of chest diseases for the follow-up of worsening dyspnea, cor pulmonale and stasis dermatitis. Erythema, localized tenderness and swelling developed on her left foot dorsum during her follow-up in the hospital. A few days later, black-colored papules with an erythematous base were observed on her foot dorsum and anterior surface of the tibia. She was diagnosed with cellulitis. Skin biopsy revealed numerous septated fungal hyphae. Preemptive amphotericin B was added to the antibacterial treatment. Within 48 h of incubation, the Scedosporium colony was isolated based on conventional methods. The fungal ribosomal RNA gene internal transcribed spacer sequence analysis revealed S.apiospermum and deposited into GenBank with accession number OM948685. The minimum inhibition concentration was defined as 1 µg/mL for amphotericin B; 16 µg/mL for fluconazole; 0.25 µg/mL voriconazole, 4 µg/mL for caspofungin, 1 µg/mL for itraconazole and 0.125 µg/mL for posaconazole on 48 h of incubation. The patient was transferred to the intensive care unit due to the deterioration of her general condition with the diagnosis of sepsis. Antimicrobial treatment was modified to caspofungin/ voriconazole combination and imipenem administration. Hepatic failure, bone marrow suppression with severe thrombocytopenia and disseminated intravascular coagulation syndrome developed on the third day of intensive care unit stay. The patient died of severe septic shock and multiorgan failure. We also reviewed the literature presenting similar cutaneous scedosporiosis cases and discussed the results.
Naganishia globosa (formerly Cryptococcus saitoi) is an environmental basidiomycetous yeast rarely associated with human disease. We report the first case worldwide of N. globosa isolated from pleural fluid in a patient with T-cell acute lymphoblastic leukemia (T-ALL), an immunocompromised host, hospitalized in Türkiye. The isolate was identified by MALDI-TOF MS and confirmed by molecular sequencing. The patient received antifungal therapy following diagnosis. Liposomal amphotericin B, isavuconazole, fluconazole, and voriconazole were used in the patient's treatment and were modified according to drug tolerance and clinical condition. The absence of yeast growth in follow-up pleural cultures and the patient's survival 1.5 months after discharge indicate a favorable response to therapy. This case highlights the clinical relevance of this uncommon yeast in immunocompromised individuals and underscores the importance of advanced diagnostic tools for accurate identification and increased awareness of rare fungal pathogens.
The Great Irish Famine (1845–1852), triggered by the potato blight pathogen Phytophthora infestans, remains one of the most devastating examples of a plant disease reshaping human history. Once misclassified as a true fungus, P. infestans is now recognized as an oomycete, and recent genomic and pangenome studies have traced its origin to the Andean highlands. Beyond its taxonomic and evolutionary importance, the famine provides a striking prototype of how a crop pathogen can cascade into widespread malnutrition, immunosuppression, and epidemic infectious diseases such as typhus and cholera-an early case of what is now conceptualized as One Health. Modern research has further demonstrated the long-term biological and developmental consequences of famine exposure, including transgenerational health effects and epigenetic scarring. At the same time, socio-political analyses have revealed how colonial policy, economic ideology, and structural neglect amplified the crisis. These interdisciplinary perspectives underscore the Irish Famine not only as a humanitarian disaster of the nineteenth century but also as a framework for understanding contemporary risks. In an era of accelerating climate change and globalization, the Irish Famine offers vital lessons for food security, global health, and crisis governance. Advances in biotechnology-including CRISPR-mediated breeding of resistant potato varieties-and genomic surveillance of plant pathogens directly draw from the legacy of this tragedy. By revisiting the Great Irish Famine through molecular, medical, and ethical lenses, this review highlights its enduring relevance as a prototype for pathogen-driven humanitarian crises and as a source of One Health lessons for the future.
Invasive infections due to Magnusiomyces/Saprochaete species are an emerging problem in immunocompromised patients and are often underrecognized because of misidentification and intrinsic resistance to some antifungals. This multicenter study investigated the species distribution, antifungal susceptibility patterns, and key virulence traits of clinical isolates from Türkiye. A total of 133 clinical isolates collected between 2010 and 2024 from 18 hospitals in 10 cities were identified by MALDI-TOF MS and ITS/LSU sequencing. MICs of amphotericin B, fluconazole, voriconazole, itraconazole, posaconazole, and flucytosine were determined using the EUCAST broth microdilution method. Biofilm formation and esterase, caseinase, secreted aspartyl proteinase, phospholipase, and hemolysin activities were assessed phenotypically. Sequencing identified 107 isolates (80.4%) as Magnusiomyces capitatus and 26 (19.6%) as Magnusiomyces clavatus, MALDI-TOF MS identified 106 (79.7%) as M. capitatus and 27 isolates (20.3%) as M. clavatus. There was 99.2% agreement between MALDI-TOF MS and sequencing results. Voriconazole, amphotericin B, and posaconazole showed the lowest MICs, whereas fluconazole displayed wide MIC ranges and limited activity. Overall, 97.7% of isolates were strong biofilm producers, with significantly higher biofilm production in M. capitatus. In contrast, M. clavatus showed higher caseinase and esterase activity. This study provides the most extensive multicenter dataset on Magnusiomyces/Saprochaete in Türkiye and underscores their considerable pathogenic potential through strong biofilm formation and tissue-degrading enzyme activities. Accurate species-level identification using MALDI-TOF MS supported by molecular methods is essential, and limited fluconazole activity suggests that voriconazole and amphotericin B should be prioritized in species-guided treatment strategies.
Introduction: Candidozyma (Candida) auris is a significant pathogen in healthcare-associated infections due to its multidrug resistance and high environmental persistence. This study aimed to investigate the survival duration of C. auris on various inanimate surfaces and compare it with other Candida species. Materials and Methods: A total of seven Candidozyma (Candida) strains-including the reference strain CDC B11903 (Clade IV)-and four different Candida species [Candida albicans, Candida krusei (Pichia kudriavzevii), Candida tropicalis, Candida parapsilosis] were used. Eight hospital-relevant surfaces (wood, glass, plastic, phone, keyboard, door handle, glove, and light switch) were contaminated with yeast suspensions at a concentration of 1010 cells/mL. Samples were collected on days 0, 1, 3, 5, 7, and 14 using sterile swabs and cultured on Sabouraud dextrose agar and sheep blood agar to assess viability. Biofilm-forming capacity was evaluated in 96-well microplates using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Results: C. auris remained viable on all tested surfaces for up to 14 days. In contrast, some of the other Candida species lost viability after day seventh no significant difference was observed among surface types regarding C. auris survival duration. All C. auris isolates were biofilm-positive. Conclusion: The prolonged environmental survival of C. auris highlights the necessity for strict and consistent infection control measures. These findings emphasize the importance of revisiting cleaning and disinfection strategies in healthcare settings.
Background: Hospital indoor environments contain a wide variety of microorganisms. Bacteria, viruses, and fungi in these environments can cause serious healthcare-associated infections in patients. The aim of this study is to show the mycoflora of the hospital by evaluating the distribution of fungal species in hospital indoor air, water, and surfaces. Methods: Air, water, and surface were sampled for fungi at Gazi University Hospital, using active air method, water collection, and swabbing, during a five-month period in 2022-2023. A total of 22 hospital wards were surveyed; overall, 110 air samples, 66 water samples, and 45 surface samples were collected. Results: A total of 1331 fungal colonies were isolated from indoor air, predominantly Penicillium (57.7%) and Cladosporium (31.6%). From outdoor air (n = 471), Cladosporium (66.9%) and Penicillium (22.5%) were most common. Median colony counts per 500 L of air were 11.5 indoors and 30.0 outdoors (range: 4–21.1 and 9–55.6, respectively. Fungal diversity, as evaluated by the Shannon index, peaked in March for both environments. Fungal growth was observed in 17 of 66 water samples (26.0%), with a total of 225 colonies recovered. Penicillium spp. accounted for the majority (85.7%), followed by Exophiala (8.0%) and Aspergillus (5.0%).Among 45 surface samples, only 3 (6.0%) yielded fungal isolates, indicating low environmental fungal burden on high-touch surfaces. Conclusion: The findings demonstrate that hospital environments, especially air and water sources, are significantly colonized by diverse fungal genera—predominantly Penicillium and Cladosporium—highlighting the importance of routine environmental mycological monitoring to mitigate potential nosocomial risks.
Candidozyma (Candida) auris has emerged as a multidrug-resistant pathogen with the capacity to persist in healthcare environments. This study investigated bidirectional interactions between biocidal exposure and antifungal susceptibility, including both minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs), in a real-life disinfection scenario, and further evaluated membrane dynamics and efflux pump activity using rhodamine 6G (R6G) uptake/efflux assays. Four clinical isolates and one reference strain were exposed to ethanol (EtOH), chlorine (CHLOR), chlorhexidine (CHX), and triclosan (TRC) for 30 s, 5 min, and 24 h. Post-exposure MIC and MFC values were determined for antifungals-amphotericin B (AMB), voriconazole (VOR), and anidulafungin (ANI)-as well as for the same biocides, following CLSI M27-A3 guidelines. Data were expressed as log₂ fold changes relative to baseline. All experiments were performed in technical triplicates to ensure reproducibility of MIC/MFC measurements. Statistical analyses were conducted using biological comparisons across the five parental isolates and their corresponding post-exposure derivatives. In this exploratory proof-of-concept study, a total of 64 isolate-condition datasets derived from five parental C. auris isolates were evaluated under 12 biocidal exposure conditions, allowing assessment of time-dependent adaptive susceptibility shifts across multiple exposure scenarios. In total, 30 short-term (30 s / 5 min) and 2 long-term (24 h) derivatives were generated from 4 different biocides (EtOH, CHX, TRC, and limited CHLOR data). All 32 biocide-exposed isolates underwent MIC/MFC testing against three antifungals (AMB, VOR, ANI) and three main biocides (EtOH, CHX, TRC), followed by biocide-free serial passaging to assess stability. Baseline MIC distributions were as follows: AMB 0.25-2 µg/mL, VOR 4-16 µg/mL, and ANI 0.01-0.25 µg/mL. After exposure, VOR MICs showed significant reduction to 3.05-4.22 mg/L with TRC exposure being nominally significant before FDR adjustment (raw p=0.043). AMB remained stable (0.47-0.67 mg/L, all p>0.05), while ANI showed non-significant variability in MIC values to 0.04-0.09 mg/L (non-significant, p>0.05). Biocidal MICs also showed changes: EtOH remained heterogeneous (p>0.05), CHX decreased significantly with CHX pre-exposure (p=0.042), and TRC showed non-significant increases. Biocidal exposure produced agent-specific antifungal effects: ANI demonstrated modest non-significant directional shifts in MIC values across all biocides, AMB remained stable with heterogeneous responses, and VOR displayed significant MIC reduction only with TRC exposure. TRC and CHX yielded the most consistent effects in both antifungal and biocidal susceptibility. R6G assays suggested alterations in efflux activity after TRC and CHX exposure, whereas EtOH impaired efflux. Most changes decreased after drug-free passages, indicating adaptive rather than fixed resistance. C. auris demonstrates dynamic and mostly reversible tolerance patterns affecting both antifungals and biocides. R6G assays provided indirect functional observations consistent with altered membrane transport dynamics following biocidal exposure, which may have contributed to the observed adaptive susceptibility shifts. The observed susceptibility shifts highlights the adaptive potential of this pathogen under disinfection stress and underscores the need to consider cross-tolerance when designing infection control strategies in healthcare settings.
Candida auris is an emerging fungal pathogen that has become a critical global health concern due to its high antifungal resistance and potential to cause nosocomial outbreaks. Since its initial identification in Japan in 2009, C. auris has spread rapidly, posing significant treatment challenges across various healthcare settings worldwide. The biofilm formation ability of C. auris enhances its resilience against disinfectants and antifungal agents, complicating infection control in healthcare environments. This consensus report was developed by a collaboration between several Turkish medical societies including the Turkish Society of Infectious Diseases and Clinical Microbiology Specialty (EKMUD), the Turkish Society of Anesthesiology and Reanimation (TARD), the Turkish Intensive Care Society (TYBD), the Infectious Diseases - International Research Initiative (ID-IRI), the Clinical Microbiology Specialist Society (KLIMUD), the Turkish Microbiology Society (TMC), and the Public Health Institution of Türkiye (PHIT) under the Ministry of Health. The report provides a comprehensive overview of C. auris and its management, with a focus on the epidemiology, antifungal resistance mechanisms, recommendations for diagnostic and therapeutic challenges, infection control and prevention measures, and surveillance of C. auris. This consensus report aims to establish standardized diagnostic protocols, improve national surveillance systems, and promote effective infection control measures to mitigate C. auris-related health risks in Türkiye. It also offers comprehensive national recommendations and addresses the need for interinstitutional collaboration, improve public health, and strengthen the healthcare response to this pathogen.
Candidozyma (Candida) auris is a multidrug-resistant yeast capable of causing persistent outbreaks in healthcare settings. Its reduced susceptibility to both antifungals and biocides poses a direct threat to infection control and hospital hygiene, as biocides remain the cornerstone of surface disinfection and outbreak containment. This study aimed to construct a decision tree to predict biocide susceptibility and identify key predictive parameters using machine learning. Virulence factors were evaluated in 55 C. auris strains isolated from a state hospital in Türkiye that were identified by MALDI-TOF and verified by DNA sequencing. CLSI guidelines were followed in determining the antifungal MICs. The z -score method was used to standardize and numerically code phenotypic data. The Random Forest Regressor was used to analyze feature importance. Resistance thresholds were defined as triclosan ≥ 0.5 µg/mL, benzalkonium ≥ 150 µg/mL, chlorhexidine ≥ 1.0 µg/mL, and chlorine ≥ 0.03 µg/mL. As all strains were benzalkonium-resistant, these data were excluded. Anidulafungin MIC was the strongest predictor of biocide sensitivity, followed by amphotericin B, flucytosine, and isavuconazole, while other virulence factors showed little or no value. This proof-of-concept study demonstrates, for the first time, that a decision tree model trained on antifungal MIC profiles can predict the susceptibility of C. auris strains to triclosan, chlorine, and chlorhexidine. Although biocide susceptibility testing was performed to establish reference thresholds, the final predictive framework relied solely on anidulafungin MIC values, suggesting that such models may reduce the need for routine biocide testing in future surveillance studies.
Candidozyma auris is an emerging multidrug-resistant fungal pathogen responsible for nosocomial outbreaks worldwide. In addition to antifungal resistance, its ability to persist in the hospital environment and tolerate commonly used biocides presents a critical challenge for infection control. However, the relationship between biocide tolerance, antifungal resistance, and virulence traits in C. auris remains poorly understood. In this study, 47 C. auris Clade 1 isolates were evaluated using phenotypic and genotypic methods. ITS region sequencing was performed using Oxford Nanopore technology. Susceptibility testing was conducted for seven antifungal agents and four biocides using the CLSI reference microdilution method. Virulence factors including biofilm formation, secreted aspartyl proteinase, esterase, caseinase, phospholipase, and hemolysis were assessed. All isolates were identified as Clade 1. MIC values for antifungals ranged from 0.015 to 64 µg/mL, and for biocides from 0.0078 to 128 mg/L. Fluconazole resistance was found in 31
Kandidemilerde etken tür dağılımında ve antifungal duyarlılık durumundaki değişimler, hastalarda prognozu etkileyebilmektedir. Bu çalışma, COVID-19 pandemisi öncesi (2016-2019) ve sonrası (2020-2024) dönemlerde kan kültürlerinden izole edilen mantar türlerinin dağılımlarını ve antifungal duyarlılıklarını karşılaştırmayı amaçlamaktadır.Çalışmada, Gazi Üniversitesi Tıp Fakültesi Tıbbi Mikrobiyoloji Laboratuvarı'nda 2016-2024 yılları arasında kan kültürlerinden izole edilen mantar türleri değerlendirilmiştir. Kan kültürleri COVID-19 öncesi ve COVID-19 sonrası dönemde BACT/ALERT® 3D cihazında inkübe edilmiştir. Üreyen mantarların tanımlanmasında pandemiden önce fenotipik yöntemler (ID32C) kullanılırken, pandemi sonrası dönemde VITEK® MS (MALDI-TOF MS) sisteminden yararlanılmıştır. Antifungal duyarlılık testleri CLSI M27-A3 mikrodilüsyon referans yöntemiyle yapılmıştır.Gazi Üniversitesi Hastanesi’nde 2016-2019 ve 2020-2024 dönemlerinde alınan toplam 148734 kan kültürünün analizi yapılmıştır. COVID-19 öncesi dönemde pozitif kültür oranı %16 (8397/53835) ve mantar pozitifliği %5 (391/8397) iken, pandemi sonrası dönemde bu oranlar sırasıyla %17 (16.572/94.899) ve %5 (845/16.572) olarak saptanmıştır. En sık izole edilen dört tür her iki dönemde Candida albicans (%40→%39), Nakaseomyces glabratus (%19→%18), Candida parapsilosis (%14→%23) ve Candida tropicalis (%9→%7) olmuş, C. parapsilosis’teki artış istatistiksel olarak anlamlı bulunmuştur (p=0.011). MİK90 değerleri esas alındığında flukonazol için C. tropicalis’te (4→8 µg/ml), vorikonazol için N. glabratus ve C. tropicalis’te (sırasıyla 0.25→2 ve 0.25→4 µg/ml), amfoterisin B için ise C. albicans ve C. parapsilosis’te (0.25→1 µg/ml) artış izlenmiştir. Bu bulgular, bazı türlerde antifungal duyarlılığın azaldığını ve dikkatli izlenmesi gerektiğini göstermektedir.Pandemi öncesi ve sonrası dönemde etken dağılımlarında sınırlı farklılıklar izlenmiş, antifungal direnç açısından dikkat çekici artışlar gözlemlenmiştir. Klinik mikrobiyoloji laboratuvarlarının düzenli aralıklarla tür ve duyarlılık dağılımlarını değerlendirmesi önerilmektedir.
Background: Invasive fungal infections (IFIs) remain a major cause of morbidity and mortality among immunocompromised patients, despite advances in antifungal therapy. Conventional diagnostics are limited, highlighting the need for novel biomarkers. Circulating microRNAs (miRNAs) and cell-free DNA (cfDNA) have emerged as promising tools due to their roles in immune regulation, pathogen–host interactions, and disease monitoring. This systematic review and meta-analysis evaluate their diagnostic and prognostic potential in fungal infections. Methods: A systematic search of PubMed, Web of Science, SCOPUS, and EMBASE was conducted up to May 2025 in line with PRISMA guidelines (PROSPERO protocol CRD42021287150). Eligible studies included clinical research on confirmed fungal infections assessing cfDNA or miRNAs. Random-effects meta-analyses were performed for cfDNA, and miRNA findings were synthesized descriptively. Results: In total, 526 studies were included. cfDNA positivity was observed in 12% of all tested samples (95% CI: 0.06–0.22) and in 79% of patients with proven fungal infections (95% CI: 0.62–0.90), supporting its value as a minimally invasive, culture-independent diagnostic marker. Six studies on miRNAs identified disease-specific signatures, including miR-132 and miRNA panels for aspergillosis, with high diagnostic accuracy (AUC ≥ 0.98). miR-146a, miR-223, and miR-545 further correlated with prognosis and mortality. Conclusions: cfDNA and miRNAs show strong potential for early diagnosis, prognosis, and treatment monitoring in IFIs. Standardized methodologies and large-scale validation are essential for clinical translation.