Infectious Disease Reports

4 pages, 180 KB

Open AccessEditor’s ChoiceEditorial

Raising the Bar of PK/PD Target Attainment of Beta-Lactams in Daily Clinical Practice: An Effective Strategy to Overcome Resistance Development to Novel Beta-Lactams?

by Milo Gatti and Federico Pea

Infect. Dis. Rep. 2026, 18(1), 3; https://doi.org/10.3390/idr18010003 - 23 Dec 2025

Viewed by 301

Abstract

The increase of infections caused by difficult-to-treat resistant (DTR) Gram-negatives is becoming an ever-growing remarkable issue for public health [...] Full article

26 pages, 3504 KB

Open AccessEditor’s ChoiceReview

The Evolution of Artificial Intelligence in Ocular Toxoplasmosis Detection: A Scoping Review on Diagnostic Models, Data Challenges, and Future Directions

by Dodit Suprianto, Loeki Enggar Fitri, Ovi Sofia, Akhmad Sabarudin, Wayan Firdaus Mahmudy, Muhammad Hatta Prabowo and Werasak Surareungchai

Infect. Dis. Rep. 2025, 17(6), 148; https://doi.org/10.3390/idr17060148 - 8 Dec 2025

Viewed by 600

Abstract

Ocular Toxoplasmosis (OT), a leading cause of infectious posterior uveitis, presents significant diagnostic challenges in atypical cases due to phenotypic overlap with other retinochoroiditides and a reliance on expert interpretation of multimodal imaging. This scoping review systematically maps the burgeoning application of artificial [...] Read more.

Ocular Toxoplasmosis (OT), a leading cause of infectious posterior uveitis, presents significant diagnostic challenges in atypical cases due to phenotypic overlap with other retinochoroiditides and a reliance on expert interpretation of multimodal imaging. This scoping review systematically maps the burgeoning application of artificial intelligence (AI), particularly deep learning, in automating OT diagnosis. We synthesized 22 studies to characterize the current evidence, data landscape, and clinical translation readiness. Findings reveal a field in its nascent yet rapidly accelerating phase, dominated by convolutional neural networks (CNNs) applied to fundus photography for binary classification tasks, often reporting high accuracy (87–99.2%). However, development is critically constrained by small, imbalanced, single-center datasets, a near-universal lack of external validation, and insufficient explainable AI (XAI), creating a significant gap between technical promise and clinical utility. While AI demonstrates strong potential to standardize diagnosis and reduce subjectivity, its path to integration is hampered by over-reliance on internal validation, the “black box” nature of models, and an absence of implementation strategies. Future progress hinges on collaborative multi-center data curation, mandatory external and prospective validation, the integration of XAI for transparency, and a focused shift towards developing AI tools that assist in the complex differential diagnosis of posterior uveitis, ultimately bridging the translational chasm to clinical practice. Full article

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9 pages, 1516 KB

Open AccessEditor’s ChoiceArticle

Repurposing Agents as Anti-Infective Therapeutics to Aid in the Treatment of Candida auris Infections

by Nazary Nebeluk and James B. Doub

Infect. Dis. Rep. 2025, 17(6), 144; https://doi.org/10.3390/idr17060144 - 27 Nov 2025

Viewed by 407

Abstract

Background: Candida auris is an emerging nosocomial fungal pathogen whose inherent multidrug resistance and ability to form biofilms make treatment extremely difficult. Given the limited number of therapeutic options available and the poor clinical outcomes associated with current therapeutics, this study evaluated the [...] Read more.

Background: Candida auris is an emerging nosocomial fungal pathogen whose inherent multidrug resistance and ability to form biofilms make treatment extremely difficult. Given the limited number of therapeutic options available and the poor clinical outcomes associated with current therapeutics, this study evaluated the potential of repurposing existing agents to treat C. auris infections. Methods: Six clinical C. auris isolates from a single tertiary care center were tested for in vitro susceptibility to topical agents (hypochlorous acid, chlorhexidine gluconate, sodium hypochlorite) and systemic agents (N-acetylcysteine, ethylenediaminetetraacetic acid, ethyl pyruvate). Furthermore, these six isolates were allowed to form biofilms and the ability of repurposed agents to disrupt C. auris biofilms was measured. Results: All agents except N-acetylcysteine demonstrated inhibitory activity against planktonic C. auris. With respect to C. auris biofilms, these were characterized using electron microscopy and all six agents showed statistically significant (p < 0.05) ability to disrupt biofilms over controls. Moreover, the ability to disrupt biofilms was also statistically significant (p < 0.05) when compared to use of either normal saline or amphotericin B. Discussion: These findings support the potential clinical utility of repurposing existing agents, such as Ethyl Pyruvate or EDTA, for systemic C. auris infections, or hypochlorous acid for C. auris wound infections. Yet, further studies are needed to optimize dosing parameters and evaluate in vivo efficacy and tolerability. Full article

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7 pages, 248 KB

Open AccessEditor’s ChoiceArticle

The Neutrophil/Lymphocyte Ratio Was Identified as a Marker of Severe Influenza During the 2024–2025 Outbreak in France

by Matteo Vassallo, Marion Derollez, Marc-Hadrien Veaute, Nicolas Clement, Roxane Fabre, Laurene Lotte, Yanis Kouchit, Sabrina Manni, Ursula Moracchini, Elea Blanchouin, Julie Better, Ludivine Rerolle, Raphael Chambon, Pierre Alfonsi Bertrand, Sarah Baccialone, Jerome Lemoine, Audrey Sindt and Pierre-Marie Bertrand

Infect. Dis. Rep. 2025, 17(5), 127; https://doi.org/10.3390/idr17050127 - 10 Oct 2025

Viewed by 568

Abstract

Background/Objectives: Influenza continues to cause high morbidity and mortality rates worldwide, inflicting a major burden on the public health system. There is little data available on the 2024–2025 seasonal outbreak. Moreover, biomarkers for rapidly identifying subjects at higher risk for severe forms are [...] Read more.

Background/Objectives: Influenza continues to cause high morbidity and mortality rates worldwide, inflicting a major burden on the public health system. There is little data available on the 2024–2025 seasonal outbreak. Moreover, biomarkers for rapidly identifying subjects at higher risk for severe forms are needed. Methods: We retrospectively collected hospitalization data for influenza in Cannes, France, during the 2024–2025 seasonal outbreak. Severe forms were defined as cases either requiring admission to the Intensive Care Unit (ICU) or resulting in death. They were compared to uncomplicated forms. Main demographic, clinical, radiological, and laboratory characteristics were collected for each patient. Results: From October 2024 to May 2025, 59 patients were admitted to either the Infectious Diseases Department or the ICU (56% male, age 72 years, 27% vaccinated, influenza type A 93%, symptom duration 3.5 days prior to hospitalization, 31% admissions to ICU, 14% deaths). Vaccination status did not differ between severe and uncomplicated forms. In the univariate analysis, severe forms had higher neutrophil/lymphocyte and platelet/lymphocyte ratios upon admission and included more cases of acute hepatitis, pneumonia, and oseltamivir use than uncomplicated forms. A neutrophil/lymphocyte ratio > 15 was independently associated with severity (OR_adj 8.79, 95% CI: 1.34–57.6, p = 0.023), with 40.9% sensitivity, 94.6% specificity, 81.8% positive predictive value, and 72.3% negative predictive value for predicting a severe form. Conclusions: The N/L ratio was an easy-to-perform predictive marker for influenza severity during the 2024–2025 seasonal outbreak, warranting further prospective studies Full article

7 pages, 515 KB

Open AccessEditor’s ChoiceCase Report

Cutaneous Leishmaniasis in the Immunocompromised: Diagnostic and Therapeutic Insights from a Case Documented in Central Italy

by Laura Povolo, Anna Barbiero, Michele Spinicci, Nicola Petrosillo, Alessandro Bartoloni and Lorenzo Zammarchi

Infect. Dis. Rep. 2025, 17(5), 125; https://doi.org/10.3390/idr17050125 - 8 Oct 2025

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Abstract

Introduction: Cutaneous leishmaniasis (CL) poses a number of challenges when it comes to diagnosis and treatment, due to the variety of clinical presentations that mimic other conditions and hinder the choice of the most appropriate therapeutic approach, especially in the context of immunodepression. [...] Read more.

Introduction: Cutaneous leishmaniasis (CL) poses a number of challenges when it comes to diagnosis and treatment, due to the variety of clinical presentations that mimic other conditions and hinder the choice of the most appropriate therapeutic approach, especially in the context of immunodepression. Case presentation: We present the case of a 63-year-old woman on anti-tumor necrosis factor (TNF) therapy, who underwent surgical excision for the diagnostic purposes of a chronic non-healing lesion located on her right arm. The histopathological examination revealed the presence of Leishmania amastigotes. CL relapsed in the following months, with new lesions appearing both close to the excision scar and at a different body site. At this point, in order to avoid another surgical intervention, cutaneous swabs for Leishmania Polymerase Chain Reaction (PCR) were performed on both lesions. Both samples yielded positive results, and the patient was treated with a 4-week course of miltefosine. Conclusions: These results support the use of cutaneous swabs as a highly sensitive and less invasive tool for the diagnostic workup of CL. In addition, our case prompts a reflection on the management of immunosuppressed patients with CL, with particular emphasis on the risk of reactivation or simultaneous involvement of multiple anatomical sites, thus suggesting the need for specific considerations and personalized management for this group of subjects. Full article

(This article belongs to the Section Neglected Tropical Diseases)

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13 pages, 407 KB

Open AccessEditor’s ChoiceReview

Public Health Impact of the MVA-BN Vaccine During the 2022 Mpox Outbreak: A Systematic Review

by Sarah C. Katsandres, Suzanne K. Scheele, Takako Kiener and Lisa Bloudek

Infect. Dis. Rep. 2025, 17(5), 124; https://doi.org/10.3390/idr17050124 - 7 Oct 2025

Cited by 1 | Viewed by 854

Abstract

Background/Objectives: Previously endemic to sub-Saharan Africa, mpox has since emerged globally, resulting in more than 150,000 cases in over 100 countries in the 2022 outbreak. The Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is licensed and recommended for at-risk populations in many countries and [...] Read more.

Background/Objectives: Previously endemic to sub-Saharan Africa, mpox has since emerged globally, resulting in more than 150,000 cases in over 100 countries in the 2022 outbreak. The Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is licensed and recommended for at-risk populations in many countries and received World Health Organization (WHO) pre-qualification in September 2024. Methods: We conducted this systematic literature review (SLR) to compare analyses, published from 2022 through 2024, of cases averted due to mpox vaccination during the 2022 outbreak to assess the feasibility of estimating the impact on the United States (US). The search included studies that utilized reported case data from any country. Results: Nine studies were identified. Four estimated the impact of the vaccine as directly modeled in the 2022 outbreak, and cases averted ranged from 10% to 79%. One assessed the projected impact on future outbreaks. Four estimated the impact of hypothetical vaccination strategies. Only one model utilized assumptions appropriate for the US outbreak and population, to allow for an estimate of US cases averted (53,499 cases averted due to the synergistic effects of the vaccine and behavioral changes, with 8096 due to the mpox vaccine alone and 5478 due to behavioral changes alone). Conclusions: Variation in estimates for the impact of the vaccine can typically be explained by differing model approaches, assumptions, inputs, and epidemic peaks and vaccination campaign roll-out. Most models were not generalizable to the US outbreak and population, but one yielded a reasonable estimate. Nevertheless, all models emphasized the importance of vaccination combined with other public health interventions. Full article

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16 pages, 648 KB

Open AccessEditor’s ChoiceReview

Clean to Prevent, Monitor to Protect: A Scoping Review on Strategies for Monitoring Cleaning in Hospitals to Prevent HAIs

by Biagio Santella, Antonio Donato, Luigi Fortino, Vittoria Satriani, Rosaria Flora Ferrara, Emanuela Santoro, Walter Longanella, Gianluigi Franci, Mario Capunzo and Giovanni Boccia

Infect. Dis. Rep. 2025, 17(5), 120; https://doi.org/10.3390/idr17050120 - 21 Sep 2025

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Abstract

Background/Objectives: Hospital environmental contamination represents a significant source of healthcare-associated infections, yet standardized monitoring approaches are still inconsistent globally. This scoping review aimed to find and assess various tools and strategies used to monitor hospital environmental cleaning and disinfection practices, mapping current evidence [...] Read more.

Background/Objectives: Hospital environmental contamination represents a significant source of healthcare-associated infections, yet standardized monitoring approaches are still inconsistent globally. This scoping review aimed to find and assess various tools and strategies used to monitor hospital environmental cleaning and disinfection practices, mapping current evidence and finding research gaps to inform evidence-based recommendations for healthcare facilities. Methods: Following PRISMA Scoping Review guidelines, we conducted comprehensive searches on PubMed and Scopus databases from 2010–2025 using terms related to environmental monitoring, surface sampling, air sampling, and infection control in hospital settings. Eighteen studies met inclusion criteria; data were extracted using standardized forms and synthesized narratively, organizing findings by monitoring approach categories. Results: These studies revealed diverse monitoring approaches including fluorescent markers (22.2%), ATP bioluminescence assays (33.3%), microbiological methods (44.4%), and direct observation techniques (27.8%). MRSA was the most frequently targeted pathogen (55.6%), with limited attention to Gram-negative multidrug-resistant organisms and fungi. Studies showed significant variability in pass/fail thresholds (ATP: 50–500 RLU) and lack of standardized benchmarks. Recent research (50% post-2021) increasingly incorporates molecular techniques and digital technologies, though implementation remains resource intensive. Conclusions: A multimodal approach combining visual inspection, ATP assays, and microbiological methods appears most effective for comprehensive environmental monitoring. Critical gaps include lack of standardized thresholds, limited pathogen diversity focus, and insufficient integration of emerging digital technologies. Future research should focus on setting universal standards, expanding pathogen coverage, and assessing cost-effective monitoring strategies, all while ensuring legal compliance with hygiene regulations to enhance patient safety. Full article

(This article belongs to the Special Issue Containment Strategies of Infectious Diseases: Epidemiology, Surveillance and Prophylaxis)

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4 pages, 202 KB

Open AccessEditor’s ChoiceEditorial

Recombinant Yeast-Based Vaccines: Importance and Applications

by Ravinder Kumar

Infect. Dis. Rep. 2025, 17(5), 118; https://doi.org/10.3390/idr17050118 - 18 Sep 2025

Cited by 1 | Viewed by 873

Abstract

Vaccines are biological preparations used to elicit an immune response, in order to prevent future infections or minimize damage from possible future infection [...] Full article

8 pages, 465 KB

Open AccessEditor’s ChoiceBrief Report

Pathways to Diagnose Infectious Pulmonary Vascular Disease in Rural Mozambique

by Yolanda Sabino, Cizália Ribeiro, Joshua Mungue and Ana Olga Mocumbi

Infect. Dis. Rep. 2025, 17(5), 116; https://doi.org/10.3390/idr17050116 - 15 Sep 2025

Viewed by 633

Abstract

Background: Schistosomiasis, HIV, and tuberculosis frequently lead to pulmonary hypertension in low- and middle-income countries. Lack of specific testing and limited access to right heart catheterization hamper confirmation of the etiology of pulmonary hypertension due to schistosomiasis. In addition, low health literacy and [...] Read more.

Background: Schistosomiasis, HIV, and tuberculosis frequently lead to pulmonary hypertension in low- and middle-income countries. Lack of specific testing and limited access to right heart catheterization hamper confirmation of the etiology of pulmonary hypertension due to schistosomiasis. In addition, low health literacy and poor socioeconomic status further compromise prevention, early diagnosis, and treatment. Clinical algorithms for early screening, including hand-held echocardiography and point-of-care testing performed by non-specialists, are needed in rural Sub-Saharan Africa to decentralize care and improve outcomes. Methods: We describe a case of pulmonary hypertension diagnosed in a child living in Mozambique, to discuss the challenges for the diagnosis of infectious pulmonary arterial hypertension in rural settings in Africa, based on a short literature review. Full article

(This article belongs to the Special Issue Pulmonary Vascular Manifestations of Infectious Diseases)

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15 pages, 1891 KB

Open AccessEditor’s ChoiceReview

Technical Challenges in Studying Infectious Disease-Associated Pulmonary Hypertension in Low- and Middle-Income Countries with Limited Resources

by Jennifer van Heerden, Irina Mbanze, Elizabeth Louw, Olukayode Aremu, Anastase Dzudie, Ana Mocumbi, Threnesan Naidoo, Brian Allwood and Friedrich Thienemann

Infect. Dis. Rep. 2025, 17(5), 109; https://doi.org/10.3390/idr17050109 - 10 Sep 2025

Cited by 1 | Viewed by 826

Abstract

Background: Pulmonary hypertension (PH) disproportionately affects those residing in low- and middle-income countries (LMICs). Given that these countries also have a high prevalence of infectious diseases, many cases of PH are either directly or indirectly related to infectious etiologies. Despite this correlation, the [...] Read more.

Background: Pulmonary hypertension (PH) disproportionately affects those residing in low- and middle-income countries (LMICs). Given that these countries also have a high prevalence of infectious diseases, many cases of PH are either directly or indirectly related to infectious etiologies. Despite this correlation, the precise burden of infectious disease-associated PH is largely underappreciated due to a lack of diagnostic resources, a shortage of clinical expertise to carry out right heart catheterization and poor access to healthcare facilities in many low- and middle-income settings. Methods: In this narrative review, we highlight the significant burden of infectious disease-associated PH in LMICs, outline the technical challenges faced by LMICs when diagnosing PH, and propose possible solutions for diagnosing PH in resource-constrained settings. Conclusions: Low-cost and sustainable solutions for infectious disease-associated PH in LMICs should be prioritized. Meaningful solutions require collaborative efforts and capacity building in LMICs. Full article

(This article belongs to the Special Issue Pulmonary Vascular Manifestations of Infectious Diseases)

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17 pages, 1604 KB

Open AccessEditor’s ChoiceArticle

Health Disparities in Central Line-Associated Bloodstream Infections: Analysis of the U.S. National Inpatient Sample Database (2016–2022)

by Nicholas Mielke, Ryan W. Walters and Faran Ahmad

Infect. Dis. Rep. 2025, 17(5), 105; https://doi.org/10.3390/idr17050105 - 28 Aug 2025

Viewed by 1316

Abstract

Introduction: Central line-associated bloodstream infections (CLABSIs) are a major cause of morbidity and mortality, yet health disparities in CLABSI incidence and outcomes remain understudied. This study evaluates these disparities and their impact on CLABSI rates, in-hospital mortality, hospital length of stay (LOS), and [...] Read more.

Introduction: Central line-associated bloodstream infections (CLABSIs) are a major cause of morbidity and mortality, yet health disparities in CLABSI incidence and outcomes remain understudied. This study evaluates these disparities and their impact on CLABSI rates, in-hospital mortality, hospital length of stay (LOS), and costs using the National Inpatient Sample (NIS) from 2016 to 2022. Methods: We conducted a retrospective analysis of adult hospitalizations using the NIS database that included central venous catheter placement and identified CLABSI using AHRQ’s Patient Safety Indicator 07. Primary outcomes included CLABSI incidence and in-hospital mortality; secondary outcomes were LOS and inflation-adjusted hospital costs. Outcomes were analyzed using logistic and lognormal regression models, focusing on demographic and clinical variables that included sex, race, socioeconomic status, and insurance type. Results: Among 11.5 million CVCs placed between 2016 and 2022, 6.56 million met CLABSI eligibility criteria, with 1 in 400 (0.25%) complicated by CLABSI. Blacks had 29.8% higher adjusted odds of CLABSI than Whites (p < 0.001), whereas Medicaid beneficiaries had 18.4% higher odds compared to those privately insured (p = 0.002). CLABSI was associated with a 97% increase in LOS and an 82% increase in hospital costs (both p < 0.001). In-hospital mortality was 13.3% and did not differ significantly by CLABSI status after adjustment. Discussion: Racial and socioeconomic disparities persist in CLABSI incidence and healthcare resource utilization, with Blacks and Medicaid beneficiaries at the highest risk. Although CLABSI rates returned to pre-pandemic levels in 2022, associated costs and LOS remained elevated. Further research and targeted prevention strategies are needed to reduce health disparities and improve patient outcomes. Full article

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11 pages, 910 KB

Open AccessEditor’s ChoiceArticle

Antimicrobial Effect of Gentamicin/Heparin and Gentamicin/Citrate Lock Solutions on Staphylococcus aureus and Pseudomonas aeruginosa Clinical Strains

by Daniel Salas-Treviño, Arantxa N. Rodríguez-Rodríguez, María T. Ramírez-Elizondo, Magaly Padilla-Orozco, Edeer I. Montoya-Hinojosa, Paola Bocanegra-Ibarias, Samantha Flores-Treviño and Adrián Camacho-Ortiz

Infect. Dis. Rep. 2025, 17(4), 98; https://doi.org/10.3390/idr17040098 - 6 Aug 2025

Viewed by 1248

Abstract

Background/Objectives: Hemodialysis catheter-related bloodstream infection (HD-CRBSIs) is a main cause of morbidity in hemodialysis. New preventive strategies have emerged, such as using lock solutions with antiseptic or antibiotic capacity. In this study, the antimicrobial effect was analyzed in vitro and with a catheter [...] Read more.

Background/Objectives: Hemodialysis catheter-related bloodstream infection (HD-CRBSIs) is a main cause of morbidity in hemodialysis. New preventive strategies have emerged, such as using lock solutions with antiseptic or antibiotic capacity. In this study, the antimicrobial effect was analyzed in vitro and with a catheter model of lock solutions of gentamicin (LSG), gentamicin/heparin (LSG/H), and gentamicin/citrate (LSG/C) in clinical and ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The formation, minimum inhibitory concentration, and minimum inhibitory concentration of the biofilm and minimum biofilm eradication concentration of the lock solutions were determined. Additionally, colony-forming unit assays were performed to evaluate the antimicrobial efficacy of the lock solutions in a hemodialysis catheter inoculation model. Results: The minimum inhibitory concentration (MIC) of planktonic cells of both P. aeruginosa and S. aureus for LSG/H and LSG/C was 4 µg/mL. In the minimum biofilm inhibitory concentration (MBIC) tests, the LSG/H was less effective than LSG/C, requiring higher concentrations for inhibition, contrary to the minimum biofilm eradication concentration (MBEC), where LSG/H was more effective. All lock solutions eradicated P. aeruginosa biofilms in the HD catheter model under standard conditions. Nevertheless, under modified conditions, the lock solutions were not as effective versus ATCC and clinical strains of S. aureus. Conclusions: Our analysis shows that the lock solutions studied managed to eradicate intraluminal mature P. aeruginosa in non-tunneled HD catheters under standard conditions. Biofilm inhibition and eradication were observed at low gentamicin concentrations, which could optimize the gentamicin concentration in lock solutions used in HD catheters. Full article

(This article belongs to the Special Issue Prevention, Diagnosis and Treatment of Healthcare-Associated Infections)

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27 pages, 1161 KB

Open AccessEditor’s ChoiceReview

Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives

by Francesco Branda, Nicola Petrosillo, Giancarlo Ceccarelli, Marta Giovanetti, Andrea De Vito, Giordano Madeddu, Fabio Scarpa and Massimo Ciccozzi

Infect. Dis. Rep. 2025, 17(4), 91; https://doi.org/10.3390/idr17040091 - 1 Aug 2025

Cited by 4 | Viewed by 10132

Abstract

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current [...] Read more.

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

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9 pages, 350 KB

Open AccessEditor’s ChoiceArticle

Clostridioides difficile Infection in the United States of America—A Comparative Event Risk Analysis of Patients Treated with Fidaxomicin vs. Vancomycin Across 67 Large Healthcare Providers

by Sebastian M. Wingen-Heimann, Christoph Lübbert, Davide Fiore Bavaro and Sina M. Hopff

Infect. Dis. Rep. 2025, 17(4), 87; https://doi.org/10.3390/idr17040087 - 23 Jul 2025

Viewed by 1593

Abstract

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was [...] Read more.

Background/Objectives: Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea in the inpatient and community setting. Real-world data outside the strict environment of randomized controlled trials (RCTs) are needed to improve the quality of evidence. The aim of this study was to compare different clinical outcomes of CDI patients treated with fidaxomicin with those treated with vancomycin using a representative patient population in the United States of America (USA). Methods: Comprehensive real-world data were analyzed for this retrospective observational study, provided by the TriNetX database, an international research network with electronic health records from multiple USA healthcare providers. This includes in- and outpatients treated with fidaxomicin (FDX) or vancomycin (VAN) for CDI between 01/2013 and 12/2023. The following cohorts were compared: (i) patients treated with fidaxomicin within 10 days following CDI diagnosis (FDX group) vs. (ii) patients treated with vancomycin within 10 days following CDI diagnosis (VAN group). Outcomes analysis between the two cohorts was performed after propensity score matching and included event risk and Kaplan–Meier survival analyses for the following concomitant diseases/events occurring during an observational period of 12 months following CDI diagnosis: death, sepsis, candidiasis, infections caused by vancomycin-resistant enterococci, inflammatory bowel disease, cardiovascular disease, psychological disease, central line-associated blood stream infection, surgical site infection, and ventilator-associated pneumonia. Results: Following propensity score matching, 2170 patients were included in the FDX group and VAN groups, respectively. The event risk analysis demonstrated improved outcomes of patients treated with FDX compared to VAN in 6 out of the 10 events that were analyzed. The highest risk ratio (RR) and odds ratio (OR) were found for sepsis (RR: 3.409; OR: 3.635), candidiasis (RR: 2.347; OR: 2.431), and death (RR: 1.710; OR: 1.811). The Kaplan–Meier survival analysis showed an overall survival rate until the end of the 12-month observational period of 87.06% in the FDX group and 78.49% in the VAN group (log-rank p < 0.001). Conclusions: Our comparative event risk analysis demonstrated improved outcomes for patients treated with FDX compared to VAN in most of the observed events and underlines the results of previously conducted RCTs, highlighting the beneficial role of FDX compared to VAN. Further big data analyses from other industrialized countries are needed for comparison with our observations. Full article

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12 pages, 939 KB

Open AccessEditor’s ChoiceBrief Report

Pulmonary Hypertension Secondary to Fungal Infections: Underexplored Pathological Links

by Andrea Jazel Rodríguez-Herrera, Sabrina Setembre Batah, Maria Júlia Faci do Marco, Carlos Mario González-Zambrano, Luciane Alarcão Dias-Melicio and Alexandre Todorovic Fabro

Infect. Dis. Rep. 2025, 17(4), 84; https://doi.org/10.3390/idr17040084 - 12 Jul 2025

Viewed by 1117

Abstract

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may [...] Read more.

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes. Full article

(This article belongs to the Special Issue Pulmonary Vascular Manifestations of Infectious Diseases)

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23 pages, 1088 KB

Open AccessEditor’s ChoiceReview

The Role of Type I Interferons in Tuberculosis and in Tuberculosis-Risk-Associated Comorbidities

by Florence Mutua, Ruey-Chyi Su, Terry Blake Ball and Sandra Kiazyk

Infect. Dis. Rep. 2025, 17(4), 81; https://doi.org/10.3390/idr17040081 - 8 Jul 2025

Cited by 3 | Viewed by 1901

Abstract

The identification of a type I interferon-induced transcriptomic signature in active tuberculosis suggests a potential role for these interferons in the pathogenesis of tuberculosis. Comorbidities such as human immunodeficiency virus, diabetes, systemic lupus erythematosus, end-stage renal disease, and coronavirus disease are epidemiologically linked [...] Read more.

The identification of a type I interferon-induced transcriptomic signature in active tuberculosis suggests a potential role for these interferons in the pathogenesis of tuberculosis. Comorbidities such as human immunodeficiency virus, diabetes, systemic lupus erythematosus, end-stage renal disease, and coronavirus disease are epidemiologically linked to an increased risk for reactivation of latent tuberculosis infection. Notably, type I interferons are also implicated in the pathogenesis of these conditions, with a recognizable type I interferon transcriptomic signature. The mechanisms by which type I interferons in tuberculosis-risk-associated comorbidities may drive the progression of tuberculosis or maintenance of latent infection however remain largely unknown. This review summarizes the existing literature on the increased association between type I interferons, focusing on interferon-α and -β, and the heightened risk of tuberculosis reactivation. It also underscores the similarities in the immunopathogenesis of these comorbidities. A better understanding of these mechanisms is essential to guide the development of host-directed interferon therapies and improving diagnostic biomarkers in M. tuberculosis infection. Full article

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8 pages, 206 KB

Open AccessEditor’s ChoiceCommentary

Clinical and Occupational Predictors of Mortality in Ebola Virus Disease: A Commentary from the Democratic Republic of Congo (2018–2020)

by Jean Paul Muambangu Milambo and Charles Bitamazire Businge

Infect. Dis. Rep. 2025, 17(3), 71; https://doi.org/10.3390/idr17030071 - 18 Jun 2025

Viewed by 1060

Abstract

Background: This commentary analyzes demographic, clinical, and occupational characteristics associated with Ebola virus disease (EVD) outcomes during the 2018–2020 outbreak in the Democratic Republic of Congo (DRC). Methods: A total of 3477 EVD cases were included. Descriptive statistics and univariate and multivariate Cox [...] Read more.

Background: This commentary analyzes demographic, clinical, and occupational characteristics associated with Ebola virus disease (EVD) outcomes during the 2018–2020 outbreak in the Democratic Republic of Congo (DRC). Methods: A total of 3477 EVD cases were included. Descriptive statistics and univariate and multivariate Cox regression analyses were performed to evaluate associations between clinical outcomes and patient characteristics. Comorbidity estimates and healthcare worker (HCW) occupational exposure data were incorporated based on the literature. Results: The median age was 26.5 years (SD = 16.1), with the majority (59.7%) aged 20–59. Males represented 51.3% of the cohort. Most patients (81.8%) worked in occupations that were not disease-exposing. Overall, 450 patients (12.9%) died. Although comorbidities initially appeared predictive of mortality (unadjusted HR: 3.05; 95% CI: 2.41–3.87), their effect was not statistically significant after adjustment (adjusted HR: 1.17; 95% CI: 0.87–1.59; p = 0.301). The strongest predictor of death was clinical status at admission: patients classified as “very sick” had an alarmingly high adjusted hazard ratio (HR) of 236.26 (95% CI: 33.18–1682.21; p < 0.001). Non-disease-exposing occupations were also associated with increased mortality (adjusted HR: 1.75; 95% CI: 1.33–2.31; p < 0.001). Conclusions: Despite improvements in outbreak response, mortality remains disproportionately high among patients presenting in critical condition and those outside the health sector. These findings underscore the importance of early detection strategies and enhanced protection for all occupational groups during EVD outbreaks. Full article

(This article belongs to the Topic Vector-Borne Disease Spatial Epidemiology, Disease Ecology, and Zoonoses)

16 pages, 1995 KB

Open AccessEditor’s ChoiceReview

Gut Microbiome in Pulmonary Arterial Hypertension—An Emerging Frontier

by Sasha Z. Prisco, Suellen D. Oliveira, E. Kenneth Weir, Thenappan Thenappan and Imad Al Ghouleh

Infect. Dis. Rep. 2025, 17(3), 66; https://doi.org/10.3390/idr17030066 - 9 Jun 2025

Cited by 1 | Viewed by 1953

Abstract

Pulmonary arterial hypertension (PAH) is an irreversible disease characterized by vascular and systemic inflammation, ultimately leading to right ventricular failure. There is a great need for adjunctive therapies to extend survival for PAH patients. The gut microbiome influences the host immune system and [...] Read more.

Pulmonary arterial hypertension (PAH) is an irreversible disease characterized by vascular and systemic inflammation, ultimately leading to right ventricular failure. There is a great need for adjunctive therapies to extend survival for PAH patients. The gut microbiome influences the host immune system and is a potential novel target for PAH treatment. We review the emerging preclinical and clinical evidence which strongly suggests that there is gut dysbiosis in PAH and that alterations in the gut microbiome may either initiate or facilitate the progression of PAH by modifying systemic immune responses. We also outline approaches to modify the intestinal microbiome and delineate some practical challenges that may impact efforts to translate preclinical microbiome findings to PAH patients. Finally, we briefly describe studies that demonstrate contributions of infections to PAH pathogenesis. We hope that this review will propel further investigations into the mechanisms by which gut dysbiosis impacts PAH and/or right ventricular function, approaches to modify the gut microbiome, and the impact of infections on PAH development or progression. Full article

(This article belongs to the Special Issue Pulmonary Vascular Manifestations of Infectious Diseases)

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19 pages, 7883 KB

Open AccessEditor’s ChoiceArticle

Differential Effects of Human Immunodeficiency Virus Nef Variants on Pulmonary Vascular Endothelial Cell Dysfunction

by Amanda K. Garcia, Noelia C. Lujea, Javaria Baig, Eli Heath, Minh T. Nguyen, Mario Rodriguez, Preston Campbell, Isabel Castro Piedras, Edu Suarez Martinez and Sharilyn Almodovar

Infect. Dis. Rep. 2025, 17(3), 65; https://doi.org/10.3390/idr17030065 - 6 Jun 2025

Cited by 1 | Viewed by 1478

Abstract

Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has [...] Read more.

Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has been implicated in vascular dysfunction; however, little is known about the specific effects of these proteins on the pulmonary vasculature. This study investigates the impact of Nef variants derived from HIV-positive pulmonary hypertensive and normotensive donors on pulmonary vascular cells in vitro. Methods: We utilized well-characterized Nef molecular constructs to examine their effects on cell adhesion molecule gene expression (ICAM1, VCAM1, and SELE), pro-apoptotic gene expression (BAX, BAK), and vasoconstrictive endothelin-1 (EDN1) gene expression in endothelial nitric oxide synthase (eNOS) nitric oxide and the production and secretion of pro-inflammatory cytokines over 24, 48, and 72 h post-transfections with Nef variants. Results: HIV Nef variants SF2, NA7, and PH-associated Fr17 and 3236 induced a significant increase in adhesion molecule gene expression of ICAM1, VCAM1, and SELE. Pulmonary normotensive Nef 1138 decreased ICAM1 gene expression, but had increased VCAM1. PH Nef ItVR showed a consistent decrease in ICAM1 and no changes in SELE and VCAM1 expression. Further gene expression analyses of pro-apoptotic genes BAX and BAK demonstrated that Nef NA7, SF2, normotensive Nef 1138, and PH Nef Fr8, Fr9, Fr17, and 3236 variants significantly increased gene expression for apoptosis. Normotensive Nef 1138, as well as PH Nef Fr9 and ItVR, all displayed a statistically significant decrease in BAX expression. The expression of EDN1 had a statistically significant increase in samples treated with Nef NA7, SF2, normotensive Nef 2044 and PH Nef 3236, Fr17, and Fr8. Notably, PH-associated Nef variants sustained pro-inflammatory cytokine production, including IL-2, IL-4, and TNFα, while anti-inflammatory cytokine levels remained insufficient. Furthermore, eNOS was transiently upregulated by all Nef variants except for normotensive Nef 2044. Conclusions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the complex interplay between Nef, host factors, and vascular pathogenesis according to the variants. Full article

(This article belongs to the Special Issue Pulmonary Vascular Manifestations of Infectious Diseases)

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