Search Results (116)

Background: Hyperbaric oxygen therapy (HBOT) is proposed as an adjunct in two sinonasal conditions of high morbidity: acute invasive fungal rhinosinusitis (AIFRS) and post-radiotherapy injury. Methods: We conducted a narrative review and reported it against SANRA; PubMed/MEDLINE was searched (1980–2026; 1414 records screened, 589 retained), with Cochrane, society guidance and reference screening. Results: No randomised trial has tested HBOT against sinonasal endpoints in either indication. In AIFRS the dedicated evidence is four uncontrolled series (n = 27, level 4); none reports how many candidates were unfit to pressurise, the largest synthesis did not identify HBOT as a survival predictor, and the only randomised experiment—murine—was negative. Mycology guidance supports it with marginal strength only (C; quality III), and hyperbaric indication lists omit it. For radiation injury, Cochrane 2023 reports low-certainty benefit in head-and-neck tissue, but HOPON found no reduction in osteoradionecrosis after dentoalveolar surgery (6.4% vs. 5.7%; OR 1.13, 95% CI 0.14–8.92), and pooled DAHANCA-21/NWHHT2009-1 data were non-significant (70% vs. 51% healing); all sinonasal use is extrapolated from the mandible. Middle-ear, not sinus, barotrauma is the commonest ENT complication. Conclusions: HBOT is mechanistically coherent and may be considered case-by-case within a multidisciplinary team, but it is not a standard of care in either indication; the algorithm offered here is unvalidated. Full article

Invasive aspergillosis and mucormycosis are life-threatening fungal infections characterized by high early mortality, substantial toxicity, and intensive healthcare resource utilization. While multiple antifungal therapies are recommended in international guidelines, their comparative clinical and economic value remains uncertain, particularly in resource-limited settings. We developed a hybrid decision tree and Markov model to evaluate antifungal strategies, including liposomal amphotericin B, isavuconazole, voriconazole, posaconazole, and caspofungin, from the perspective of the Colombian healthcare system over a 6-month horizon. Health states included clinical response, treatment failure, toxicity, and death. Outcomes included quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs), and net monetary benefit (NMB). Deterministic and probabilistic sensitivity analyses were performed. In invasive aspergillosis, isavuconazole provided a modest incremental benefit over voriconazole (+0.022 QALYs), driven primarily by improved tolerability, at an incremental cost of COP 3.4 million, yielding an ICER of COP 154.5 million/QALY. In mucormycosis, liposomal amphotericin B yielded greater survival benefits (+0.035 QALYs) but at substantially higher costs (ICER: COP 494.3 million/QALY). Across willingness-to-pay thresholds, isavuconazole and voriconazole demonstrated more favorable economic profiles, owing to lower toxicity and reduced hospitalizations. These findings highlight that the clinical–economic value of antifungal therapy is primarily determined by early survival gains, toxicity burden, and front-loaded costs. Strategies minimizing toxicity and hospitalization appear more efficient in constrained health systems, whereas survival-maximizing approaches may be justified in severe disease. This integrated analysis supports context-specific antifungal decision-making in the management of invasive fungal infections. Full article

Invasive fungal infections (IFIs) are associated with high morbidity and mortality, particularly in immunocompromised or critically ill patients and in those with complex comorbidities. Despite advances in mycological diagnosis and antifungal therapy, outcomes remain poor in a significant proportion of patients. In clinical practice, a poor response is often attributed to microbiological resistance. This interpretation may lead to empirical treatment escalation, combination therapy without a clear indication, increased toxicity, clinically relevant drug–drug interactions, and inefficient use of healthcare resources. However, therapeutic failure rarely results from a single mechanism. More often, it reflects the interaction among host vulnerability, pathogen characteristics, delayed, incomplete, or incorrect diagnosis, insufficient antifungal exposure, and inadequate source control. This narrative review presents a structured clinical approach to evaluating suboptimal responses in IFIs without attributing them solely to antifungal resistance. It examines cross-cutting determinants and specific patterns associated with invasive aspergillosis, invasive candidiasis and persistent candidemia, cryptococcal meningitis, mucormycosis, infections caused by rare filamentous fungi, and disseminated endemic mycoses. It also presents clinical algorithms, checklists, and potential quality indicators to distinguish true from apparent failure, identify modifiable factors, and support transparent clinical decision-making within antifungal stewardship programs. The proposed framework supports the assessment of non-response through systematic diagnostic and therapeutic reassessment, timely source control, and identification of modifiable gaps in care. Full article

Infectious diseases constitute a major public health concern and a leading cause of morbidity and mortality worldwide. The eye, by virtue of its rich vascularity and unique immunological microenvironment, is susceptible to involvement by a broad spectrum of bacterial, viral, fungal, and parasitic systemic infections, which may lead to diverse ocular and visual manifestations through direct pathogen invasion, immune-mediated mechanisms, or complications of therapy. Notable systemic infections with potential ocular involvement include tuberculosis; the spirochetal illnesses syphilis, Lyme disease, and leptospirosis; brucellosis; cat-scratch disease; leprosy; infective endocarditis; human immunodeficiency virus, cytomegalovirus, West Nile virus, and adenovirus infections; rubeola; dengue fever; candidiasis; cryptococcosis; aspergillosis; mucormycosis; toxoplasmosis; malaria; onchocerciasis; and cysticercosis. Ocular manifestations can serve as early diagnostic clues to underlying systemic infections, whereas, conversely, systemic features can help interpret ocular findings. Effective investigation and management of systemic infections benefit from a multidisciplinary approach, in which ophthalmologists can contribute substantially and help optimize both visual and overall health outcomes. Full article

Rhino-orbital mucormycosis is a rare, life-threatening opportunistic fungal infection, typically affecting immunocompromised patients. During the COVID-19 pandemic, increased cases were mainly linked to SARS-CoV-2 infection, diabetes, and corticosteroid exposure. We report a severe case in a previously healthy 44-year-old immunocompetent man who developed acute left-sided exophthalmos, ophthalmoplegia, severe visual loss, and systemic deterioration 10 days after AZD1222 COVID-19 vaccination. Clinical and radiologic findings suggested invasive rhino-orbital fungal disease, prompting immediate liposomal amphotericin B, broad-spectrum antibiotics, urgent endoscopic sinus surgery, and repeated orbital–sinonasal debridements with amphotericin B irrigation. Histopathological examination demonstrated broad aseptate hyphae with tissue necrosis, consistent with mucormycosis, while fungal culture and ITS sequencing identified Rhizopus arrhizus as the causative species. Therapy was later adjusted to include isavuconazole and antibacterial coverage for persistent inflammation and secondary colonization. Orbital and systemic improvement occurred within the first week, with globe preservation and marked proptosis reduction at 6 months, despite persistent ophthalmoplegia and residual light perception. Isavuconazole was continued for 2 years, with no recurrence during 3 years of follow-up. Although causality with vaccination cannot be established, the temporal association and biological plausibility warrant further investigation. Early suspicion and prompt combined medical–surgical management are essential in rapidly progressive orbital cellulitis. Full article

Diagnostic failure in invasive fungal infections (IFIs) remains a relevant and underrecognized cause of mortality, morbidity, delayed therapy, unnecessary antifungal exposure, and pharmacological selective pressure. Although major advances have been achieved in biomarkers, rapid diagnostic tests, molecular methods, imaging studies, and microbiological identification, timely diagnosis continues to be influenced by the interaction among host factors, pathogen-related factors, diagnostic tools, and healthcare system–related factors. This narrative review analyzes diagnostic failure in IFIs as a dynamic process that includes delayed, incorrect, and incomplete diagnosis. It examines its determinants and consequences in high-risk populations—critically ill patients, patients with hematologic diseases or hematopoietic stem cell transplant recipients, and neonates—as well as in invasive candidiasis, aspergillosis, mucormycosis, cryptococcosis, endemic mycoses, and infections caused by rare or emerging fungi. It also reviews how delayed sampling, decontextualized interpretation of biomarkers, incomplete microbiological identification, absence of antifungal susceptibility testing when clinically relevant, and fragmentation between clinical and laboratory teams contribute to adverse outcomes. Finally, it proposes a diagnostic-centered antifungal stewardship framework (AFSP-Dx) based on syndromic bundles, population-specific diagnostic algorithms, 48–72 h reassessment, and auditable indicators intended to support earlier recognition, more precise therapeutic decisions, and rational antifungal use. Full article

Background: Mucormycosis is a life-threatening angioinvasive fungal infection that primarily affects immunocompromised individuals, especially those with diabetes mellitus or hematologic malignancies. Despite its clinical importance, a comprehensive synthesis of mucormycosis cases from Türkiye is lacking. This study aimed to review and synthesize the published case reports on mucormycosis in Türkiye systematically. Materials and Methods: Mucormycosis case reports from Türkiye published between 1 January 1966 and 30 November 2024 were reviewed and analyzed, with an emphasis on demographics, clinical characteristics, treatment strategies, and outcomes. Results: A total of 199 cases from 155 publications were included. Mean age was 47.7 years, and 51.8% of patients were male. Diabetes mellitus was the most frequent underlying condition (65.8%), followed by hematologic malignancies (16.6%). Rhino-cerebral involvement was the predominant clinical form (86.4%). Histopathological confirmation was reported in 91.0% of cases, whereas microbiological confirmation was available in 47.7%. Overall mortality was 43.7%. Surgical debridement was performed in 69.3% of cases, and crude mortality was lower among patients who underwent surgery than among those who did not. Liposomal amphotericin B was the most frequently reported antifungal agent. Conclusions: This study provides a national descriptive synthesis of published mucormycosis cases from Türkiye over nearly six decades. The findings highlight the predominance of diabetes-associated rhino-cerebral disease, frequent reliance on histopathology, and the importance of combined medical–surgical management in routine practice. Because the dataset is based on heterogeneous published case reports and case series spanning a long time period, treatment-outcome findings should be interpreted descriptively. Full article

Mucormycosis is a devastating invasive fungal infection primarily caused by Mucor and Rhizopus species, presenting significant clinical challenges due to limited therapeutic options and emerging drug resistance in opportunistic yeasts such as Candida albicans. This study explores foliar endophytic fungi from Thai medicinal plants as potential reservoirs for novel bioactive metabolites targeting both fungal growth and virulence factors. We report the first isolation of Fusarium proliferatum as an endophyte from Lantana camara L. foliage (voucher number 01562), with its identity confirmed through morphological characterization and sequencing of the fungal ITS4/ITS5 regions. Antifungal susceptibility testing showed potent activity against a panel of environmental Mucorales, with minimum inhibitory concentrations (MICs) ranging from 0.3 to 1 mg/L. In dual-culture assays, F. proliferatum demonstrated significant mycelial inhibition rates of 93.30% to 93.67% against Mucor spp. and 88.67% to 93.67% against Rhizopus spp. Furthermore, the crude extract exhibited a potent anti-virulence effect by suppressing the C. albicans yeast-to-hyphal transition, achieving up to 68% germination inhibition in resistant strains. Liquid chromatography–mass spectrometry (LC-MS) analysis identified 51 secondary metabolites, including the cyclic peptide beauvericin and various polyketides and indole derivatives. These findings suggest that F. proliferatum utilizes metabolic mimicry and adaptive synergy with its host plant to produce a diverse chemical arsenal. This study positions foliar endophytes of L. camara as promising candidates for the development of dual-action therapeutics to combat invasive and resistant mycoses. Full article

Mucormycosis is a rare, invasive fungal infection associated with high mortality. This retrospective study evaluated adult mucormycosis cases followed in our clinic between 2015 and 2025. A total of 13 patients were included, with a mean age of 50.92 ± 20.65 years (range, 20–83), and 10 (76.9%) were male. The most frequent symptom was facial pain (100%). Four (30.8%) of the patients had rhino-sinusitis, and three (23%) had rhino-orbito-cerebral involvement. Seven (53.9%) of the patients had hematological malignancy, three (23%) had diabetes mellitus (DM), two (15.4%) had a history of COVID-19 pneumonia, and one (7.7%) had a history of both DM and COVID-19 pneumonia. All had elevated C-reactive protein levels. Rhizopus spp. grew in nasal/tissue cultures of three (23%) patients, and so did Mucor spp. Surgery was performed in 11 (84.6%) patients, and fungal hyphae were observed in tissue histopathology. All patients showed radiological findings of mucormycosis on imaging. All patients received Liposomal Amphotericin B, and nine (69.2%) patients received sequential posaconazole therapy. Recurrence occurred in two (15.4%) patients. A total of eight (61.5%) patients, including three (23%) patients with intracranial involvement, died. Mucormycosis is a severe infection, especially in patients with hematological malignancies or DM, despite early diagnosis and combined antifungal and surgical treatments. Full article

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies. Full article

Invasive pulmonary mold infections (IPMIs) are critical complications in immunocompromised patients, contributing significantly to morbidity and mortality. Diagnosing pathogens like Aspergillus species (spp.) and the Mucorales remains challenging due to non-specific clinical presentations and the limitations of traditional culture methods. This review provides an up-to-date synopsis of IPMI diagnostic tools, focusing on their diagnostic performance, turnaround time (TAT), and cost-effectiveness. We conducted a narrative review of the current literature regarding clinical evaluation, radiographic findings, invasive diagnostics, and non-invasive assays, including next-generation sequencing (NGS) and volatile organic compounds (VOCs). Chest computerized tomography (CT) remains a vital first step, though classic signs like the “halo” or “reverse halo” are neither sensitive nor specific. Traditional diagnostics are limited by low sensitivity and delayed results. While plasma microbial cell-free DNA (mcfDNA) NGS offers rapid TAT (24–48 h) and high specificity, its suboptimal sensitivity for Aspergillus spp. (<50%) and high cost remain significant barriers. Investigational VOC “breath tests” show promising sensitivity (77–96%) but lack standardization. Future research must prioritize the standardization of non-invasive microbiologic testing modalities, particularly those with rapid TAT such as bedside “breath tests” and high-throughput mcfDNA NGS. Development of clinical algorithms that balance cost-effectiveness with timely pathogen diagnosis based on the patient’s degree of immunosuppression is essential to improve survival in high-risk populations. Full article

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

Background and Objectives: Osteonecrosis of the jaw (ONJ) occurring after infection with SARS-CoV-2 has emerged as an increasingly reported complication in the post-COVID-19 era. Post-COVID-19 osteonecrosis of the jaw (PC-ONJ) has been described in association with both COVID-19-associated mucormycosis (CAM) and non-fungal phenotypes. This narrative review aims to synthesize and critically analyze the available evidence regarding terminology and classification, epidemiology and risk factors, pathophysiological mechanisms, clinical and imaging characteristics, diagnostic challenges, and management strategies relevant to oral and maxillofacial surgery practice. Materials and Methods: An extensive literature search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar databases. The search targeted peer-reviewed publications published between 2020 and 2025, reflecting the post-pandemic emergence of this clinical spectrum. Original studies, systematic and narrative reviews, multicenter case series, consensus guidelines, and well-documented case reports were considered. Results: Available data, largely derived from case reports and small series, demonstrate a predominance of maxillary involvement and frequent association with diabetes mellitus and systemic corticosteroid therapy. Proposed mechanisms include COVID-19-associated endothelial dysfunction, microvascular thrombosis, immune dysregulation, metabolic imbalance, and treatment-related effects. Clinically, patients may present with persistent orofacial pain, tooth mobility, exposed or probeable bone, and frequent sinonasal extension, with symptoms sometimes preceding bone exposure. Diagnostic challenges arise from the overlap with medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and chronic osteomyelitis. Imaging is essential for assessing disease extent but remains insufficient for etiologic differentiation, making histopathological examination and targeted microbiological investigations necessary, particularly to exclude invasive fungal infection. Conclusions: Management must be etiology-driven. CAM requires urgent antifungal therapy combined with surgical debridement, whereas non-fungal forms are generally managed with conservative surgery and appropriate antimicrobial stewardship. Standardized diagnostic criteria and prospective multicenter studies are needed to reduce nosological ambiguity and optimize clinical decision-making in this emerging post-viral condition. Full article

Invasive pulmonary fungal infections remain a major cause of morbidity and mortality among immunocompromised and critically ill patients. Rapid and accurate diagnosis is crucial for improving outcomes, yet conventional methods such as culture and histopathology suffer from limited sensitivity and slow turnaround times. Recently, significant progress has been made in the development and standardization of serological and molecular biomarkers that enhance the early detection of the key pulmonary fungal diseases, particularly invasive pulmonary aspergillosis and pneumocystosis. Diagnostic tools for mucormycosis, however, remain scarce. PCR tools have strong potential to significantly improve early detection, but they are not yet widely implemented, and standardized commercial assays remain limited. Accessible antigen-based tests with robust performance are highly anticipated and expected to become available soon. This review summarizes the current evidence regarding the optimal use of galactomannan, β-D-glucan and PCR-based assays, emphasizing how their performance varies according to the pathogen, the type of specimen and the host population. Specific challenges, such as differentiating colonization from infection in non-HIV Pneumocystis pneumonia or interpreting galactomannan and PCR in patients receiving mold-active prophylaxis, are highlighted. We also discuss how combining biomarkers can enhance diagnostic accuracy and support timely therapeutic decisions. A clear understanding of the strengths, limitations and appropriate interpretation of these diagnostic tools is crucial in an era of increasing host complexity, shifting fungal epidemiology, and expanding antifungal options. Full article

(1) Background: Invasive fungal diseases (IFDs) represent significant challenges in clinical practice, particularly among immunocompromised individuals, leading to substantial morbidity and mortality. The present document aims to provide evidence-based consensus for the timely initiation of antifungal treatment, focusing on early empiric approaches among immunocompromised patients. (2) Methods: A multidisciplinary expert panel of nine healthcare professionals (HCPs) reviewed the literature, including guidelines and consensus reports (2013–2023; PubMed, Scopus). The panel defined appropriate empiric antifungal approaches for invasive candidiasis, aspergillosis, and mucormycosis among hematological and critically ill patients. Consensus was defined as ≥75% agreement. (3) Results: A total of 47 statements were included. The experts recommend that early targeted antifungal therapy is critical for high-risk patients with suspected IFDs. Empiric therapy may be initiated before definitive diagnosis, considering the local fungal prevalence and the patient’s risk category. Close monitoring is essential, and switching between antifungal classes may be necessary for patients who experience deterioration or side effects. The transition from intravenous to oral therapy depends on the specific infection, the availability of therapeutic drug monitoring, and the patient’s progress. (4) Conclusions: Implementing this targeted, early approach may improve the outcomes of vulnerable patients with IFDs. Full article