Search Results (4,025)

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs. Full article

Background/Objectives: African swine fever (ASF) is a disease of domestic pigs and wild boar caused by African swine fever virus (ASFV), in which infection often leads to high morbidity and mortality. Although subunit and mRNA vaccines based on protective antigens have been explored for ASFV, their protective efficacy remains insufficient for practical ASF control, highlighting the need to identify new potential antigens capable of inducing more potent and broadly protective immune responses. Previously, we found that the antibodies against the ASFV E120R protein (pE120R) could significantly inhibit virus replication in primary porcine alveolar macrophages (PAMs). However, it is not yet known whether anti-pE120R antibodies can induce antibody-dependent cellular cytotoxicity (ADCC). Methods: In this study, we analyzed the conservation and immunogenic features of pE120R and established an HEK293T cell line with stable expression of pE120R as target cells (HEK293T-pE120R). Additionally, a co-culture system comprising target cells and peripheral blood mononuclear cells (PBMCs) was established to evaluate the ability of the anti-pE120R antibodies to induce ADCC as measured by lactate dehydrogenase (LDH) release assays. Results: The results showed that pE120R is highly conserved among different ASFV genotypes and contains multiple B-cell and T-cell epitopes. Importantly, LDH release assays demonstrated that anti-pE120R antibodies triggered NK cell-mediated ADCC. Notably, ASFV replication in HEK293T-pE120R cells was not promoted. Conclusions: In summary, pE120R was associated with antibody production in a cytotoxicity assay. The ability of this antigen to induce protective immunity, if any, requires further evaluation in vivo. Full article

Porcine Teschovirus (PTV) is a highly prevalent pathogen within swine populations, primarily associated with encephalitis, diarrhea, pneumonia, and reproductive disorders in pigs, thereby posing a significant threat to the sustainable development of the pig farming industry. In this study, a novel strain of PTV was isolated from the feces of a pig exhibiting symptoms of diarrhea, utilizing PK-15 cell lines. The structural integrity of the viral particles was confirmed via transmission electron microscopy, and the viral growth kinetics and characteristics were evaluated in PK-15 cells. High-throughput sequencing facilitated the acquisition of the complete viral genome, and subsequent phylogenetic analysis and full-genome alignment identified the strain as belonging to the PTV 2 genotype. Further investigation revealed that infection with the PTV-GXLZ2024 strain induces phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α) in PK-15 cells, indicating activation of the unfolded protein response (UPR) through the PERK pathway, with minimal involvement of the IRE1 or ATF6 pathways. Notably, ATF4 protein expression was progressively downregulated throughout the infection, while downstream CHOP protein levels remained unchanged, indicating an incomplete UPR induced by PTV-GXLZ2024. Furthermore, PERK knockdown was found to enhance the replication of PTV-GXLZ2024. This study provides critical insights into the molecular mechanisms underlying PTV pathogenesis and establishes a foundation for future research into its evolutionary dynamics and interactions with host organisms. Full article

Despite rising global reports of Acanthamoeba keratitis (AK), the incidence of AK in Switzerland remains unknown. This investigator-initiated, retrospective, multicenter study assessed the nationwide incidence of PCR- and/or culture-positive Acanthamoeba results from January 2010 to December 2023. Data were collected from all tertiary care and large ophthalmological facilities in Switzerland, fully anonymized, and aggregated by month and year. We considered all corneal scraping results, whereby the detection method was specific to local standards. We identified 271 PCR- or culture-positive Acanthamoeba cases over 14 years. Applying the population data from the Federal Statistical Office in Switzerland, this corresponds to a mean incidence of 2.29 cases per million people annually. Infections were most common in summer (87 cases, 32.1%), followed by autumn (74 cases, 27.3%), spring (60 cases, 22.1%), and winter (50 cases, 18.5%). We found no significant change in incidence across the investigated period, p = 0.47. This nationwide study reveals a low but stable incidence of AK in Switzerland, in line with other industrialized countries but well below levels reported in tropical or densely populated regions such as India or Egypt. Seasonal variation supports the influence of environmental exposure and underscores the importance of preventive measures during warmer months. Full article

Newcastle Disease (ND) is an important and notable disease among the avian infectious diseases, because of its high contagiousness, and the most virulent strains of ND virus (NDV) have impacted poultry breeders all over the world. Immunization and biosecurity measures are used to reduce ND; however, vaccination has been shown to offer protection against clinical signs but not against virus proliferation and shedding, which could have an adverse effect on the environment. The genetic basis for inherent resistance to NDV has been established, and genetic selection on existing resistance-related genetic variation can help to mitigate virus propagation. Further, understanding the genes and processes that drive the response to NDV will lay the groundwork for genetic improvement in poultry. The majority of studies on NDV susceptibility make use of phenotypic indicators such as body weight, morbidity, mortality, antibody response, and viral load. According to recent advancements in molecular genetic research, many different genes are diversely regulated in different chicken lines to NDV infection, which might be used in the future to establish disease-resistant breeding approaches. It is possible that many more genes linked to illness and resistance are still to be discovered, because the precise mechanism of resistance is not entirely understood. The enhanced genetic knowledge of chickens and the development of more advanced transgenic techniques would lead to pathogen resistance. Hence, this paper summarizes the current understanding of genetic resistance to Newcastle Disease, and we additionally highlight a few possible genes/markers connected with NDV that may improve chicken resistance to NDV infections and can be used to produce NDV-resistant chicken breeds/strains in the near future. Full article

Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options. Full article

Background: The aims of this paper are to examine the impact of the COVID-19 pandemic on the non-rational use of antibiotics and potential alterations in the antibiotic resistance profiles of multi-drug resistant (MDR) isolates of Klebsiella pneumoniae (KPN), Pseudomonas aeruginosa (PAE), and Acinetobacter baumannii (ABA). Material and Methods: This study was conducted at the tertiary University Hospital “Dr Dragisa Misovic-Dedinje” (Belgrade, Serbia) and was divided into three periods: pre-pandemic (1.4.2019–31.3.2020, period I), COVID-19 pandemic (1.4.2020–31.3.2021, period II), and COVID-19 pandemic-second phase (1.4.2021–31.3.2022, period III). Cultures were taken from each patient with clinically suspected infection (symptoms, biochemical markers of infection). All departments of the hospital were included in this study. Based on the source, all microbiological specimens were divided into 1° blood, 2° respiratory tract (tracheal aspirate, bronchoalveolar lavage fluid, throat, sputum), 3° central-line catheter, 4° urine, 5° urinary catheter, 6° skin and soft tissue, and 6° other (peritoneal fluid, drainage sample, bioptate, bile, incisions, fistulas, and abscesses). After the isolation of bacterial strains from the samples, an antibiotic sensitivity test was performed for each individual isolate with the automated Vitek^® 2 COMPACT. Antibiotic consumption testing was performed by the WHO guideline equations (ATC/DDD). Results: A total of 2196 strains of KPN, PAE, and ABA from 41,144 hospitalized patients were isolated (23.6% of the number of total isolates). The number of ABA isolates statistically increased (p = 0.021), while the number of PAE isolates statistically decreased (p = 0.003) during the pandemic. An increase in the percentage of MDR strains was observed for KPN (p = 0.028) and PAE (p = 0.027). There has been an increase in the antibiotic resistance of KPN for piperacillin–tazobactam, the third and fourth generations of cephalosporins (ceftriaxone, ceftazidime, and cefepime), all carbapanems (imipenem, meropenem, and ertapenem), and levofloxacin; of PAE for imipenem; and of ABA for amikacin. Total antibiotic consumption increased (from 755 DBD to 1300 DBD, +72%), especially in the watch and reserve group of antibiotics. The highest increases were noted for vancomycin, levofloxacin, azithromycin, and meropenem. MV positively correlated with the increased occurrence of MDR KPN (r = 0.35, p = 0.009) and MDR PAE (r = 0.43, p = 0.009) but not for MDR ABA (r = 0.09, p = 0.614). There has been a statistically significant increase in the Candida sp. isolates, but the prevalence of Clostridium difficile infection remained unchanged. Conclusions: The COVID-19 pandemic has influenced the increase in total and MDR strains of KPN, ABA, and PAE and worsened their antibiotic resistance profiles. An increase in the consumption of both total and specific antibiotics was observed, mostly of fluoroquinolones and carbapenems. A positive correlation between the number of patients on MV and an increase in MDR KPN and MDR PAE strains was noted. It is necessary to adopt and demand the implementation of appropriate antimicrobial stewardship interventions to decrease the resistance of intrahospital pathogens to antibiotics. Full article

Background: The official current guideline for Helicobacter pylori (H. pylori) eradication is to use tetracycline–bismuth-based protocols as first line treatment due to the increasing incidence of clarithromycin resistance in the last decade. The unavailability of tetracycline and bismuth-containing medicines, however, is an issue in many countries, limiting the routine use of these protocols. The value of using additional probiotics in eradication protocols is also unclear. Direct comparison data on the effect of available bismuth compounds and different probiotic strains on eradication outcome are limited. Goal: The aim of our investigation was to find optimal eradication protocols, supplementations and treatment duration for routine clinical use in our gastroenterology unit, located in a highly clarithromycin-resistant and tetracycline–bismuth-naïve area. Materials and Methods: We conducted a retrospective real-world data analysis of 402 H. pylori positive patients between 2016 and 2024. H. pylori infection was diagnosed using histological examination of gastroscopy samples obtained from the gastric antrum. For the evaluation of treatment success or failure, ¹⁴C breath tests and stool H. pylori antigen tests were performed. Data on patient characteristics and treatment protocols were collected from our electronic patient record system, and treatment success was compared between the different treatment regimes. Results: Despite the regional clarithromycin resistance, supplementing clarithromycin-based regimens with bismuth and probiotic during the 14-day treatment duration showed a high and comparable cure rate when compared to tetracycline-based regimens, which are the current first-line therapies. When tetracycline-based combination is available, it is recommended to use it with an additional probiotic to achieve the best possible outcome. Comparison of the effect of available bismuth preparations on treatment success showed no significant difference. Generally, probiotic-containing protocols are more successful, compared to those treatments without this supplement. There was no statistical difference in the cure rates amongst the four probiotic strains used, where sample size allowed statistical analysis. Furthermore, supplementation with probiotics Lactobacillus reuteri ATCC PTA 6475 or Lactobacillus reuteri Protectis^® DSM 17938 showed promising high treatment success rates (85.2% and 100.0%, respectively) in our study. Full article

Bacteria and phages have coexisted for billions of years engaging in continuous evolutionary arms races that drive reciprocal adaptations and resistance mechanisms. Among the diverse antiviral strategies developed by bacteria, modification or masking phage receptors as well as their physical removal via extracellular vesicles are the first line of defense. These vesicles play a pivotal role in bacterial survival by mitigating the effects of various environmental threats, including predation by bacteriophages. The secretion of extracellular vesicles represents a highly conserved evolutionary trait observed across all domains of life. Bacterial extracellular vesicles (BEVs) are generated by a wide variety of Gram (+), Gram (−), and atypical bacteria, occurring under both natural and stress conditions, including phage infection. This review addresses the multifaceted role of BEVs in modulating bacteria–phage interactions, considering the interplay from both bacterial and phage perspectives. We focus on the dual function of BEVs as both defensive agents that inhibit phage infection and as potential facilitators that may inadvertently enhance bacterial susceptibility to phages. Furthermore, we discuss how bacteriophages can influence BEV production, affecting both the quantity and molecular composition of vesicles. Finally, we provide an overview of the ecological relevance and efficacy of BEV–phage interplay across diverse environments and microbial ecosystems. Full article

Background/Objectives: High-risk human papillomavirus (HPV) is the principal etiological agent of cervical cancer, with distinct genotype-specific oncogenic potential. While HPV type 16 is most frequently implicated in carcinogenesis, the role of other genotypes and their interaction with sexually transmitted infections and cervico-vaginal dysbiosis is gaining recognition. This study aimed to assess the genotype-specific distribution of high-risk HPV among HPV-positive women from Southern Croatia and examine associations with age and co-infections with selected microbial pathogens. Methods: We conducted a retrospective cross-sectional study on 1211 HPV-positive women (out of 3098 tested) from Split and Dalmatia County between 2023 and 2024. Cervico-vaginal swabs were tested using molecular and culture-based methods for 14 high-risk HPV genotypes and several pathogens, including Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis, and other microorganisms. In the analysis, each detected HPV genotype was also treated as a distinct line-level observation. Genotypes were grouped by phylogenetic and carcinogenic profiles, and statistical analyses—including chi-square tests and multinomial logistic regression—were performed to evaluate associations with age and co-infections. Results: Among high-risk HPV-positive women, the most frequently detected high-risk HPV genotypes were HPV 16 (23.3%), HPV 31 (22.4%), and HPV 51 (13.5%). Notably, HPV 18 was less prevalent (8.1%) and occurred at a similar frequency to HPV 58 and 68. Although younger age was significantly associated with high-risk HPV positivity (p < 0.001), no significant differences in HPV genotype group distribution were observed between age groups; however, C. trachomatis and Streptococcus agalactiae were significantly more prevalent in women aged ≤29 years (p < 0.001 and p = 0.029, respectively). Multinomial regression revealed that C. trachomatis was negatively associated with 16-related and lower-risk genotypes, while G. vaginalis showed a positive association with 16-related types. Conclusions: There is a complex interplay between high-risk HPV genotypes and microbial co-infections, which means the broader cervico-vaginal microbiome has to be considered in HPV risk assessment. The findings highlight the need for extended genotyping and microbial screening to inform regional prevention strategies. Full article

Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and significant psychosocial distress. A multidisciplinary strategy that integrates epidemiology, precise diagnostics, individualized therapy, and psychological support is essential to optimize outcomes. We performed a structured literature search in PubMed, Scopus, and Web of Science using terms “vulvar viral infection,” “HPV,” “HSV,” “molluscum contagiosum,” and “Lipschütz ulcers.” International guidelines from the UK, Europe, and Australia were reviewed, alongside reference lists of key articles. Particular attention was given to paradoxical presentations, pediatric considerations, and cost-effectiveness analyses. HPV vaccination programs have markedly reduced anogenital warts, while early PCR/NAAT for HSV accelerates targeted antiviral therapy. First-line treatments like oral acyclovir/famciclovir for HSV and topical imiquimod or podophyllotoxin (±cryotherapy) for HPV are supported by adjunctive measures for self-limiting conditions. Host factors (hormonal cycles, immune status) and local irritants modulate recurrence risk, informing anticipatory suppressive regimens and barrier-reinforcing care. Validated patient-reported outcome measures (VPAQ, DLQI, FSFI) capture pain, sexual function, and quality-of-life impacts. Health–economic evaluations underscore the long-term value of rapid diagnostics and broad vaccination. Personalized, multidisciplinary management that combines prevention, precision diagnostics, tailored therapy, psychosocial support, and economic considerations offers the greatest promise for improving clinical and quality-of-life outcomes in patients with vulvar viral infections. We aim to outline best practices for the diagnosis and management of common vulvar viral infections, providing practical guidance for clinicians to improve recognition and therapeutic decision-making. Full article

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

Pathogenic bacteria have developed different ways to cause infections. One strategy involves using components from host cells. This study looks at the role of the cytoskeleton in the human colon adenocarcinoma Caco-2 and neonatal non-transformed epithelial H4 cell lines during bacterial invasion. The bacteria studied include Cronobacter malonaticus, Cronobacter sakazakii, and E. coli K1, as they are associated with known diseases. Salmonella enteritidis 358 served as a positive control and E. coli K12 as a negative control for the invasion experiments. Before the invasion experiments, cell lines were treated with microfilament inhibitors, specifically Cytochalasin D, and microtubule inhibitors, such as Colchicine, Nocodazole, Vinblastine, and Taxol. The results showed that Cytochalasin D reduced about 60–80% of Cronobacter invasion into H4 cells and 50% of E. coli K1 invasion. In contrast, Colchicine reduced the invasion of some strains to just 2% compared to untreated cells. Meanwhile, Nocodazole and Taxol increased the invasion of C. sakazakii 709 and C. malonaticus 1569 into H4 cells by about 140% and 160%, respectively, while slightly inhibiting other strains. In Caco-2 cells, certain strains exhibited increased invasion due to Cytochalasin D, Vinblastine, and Colchicine treatment. This led to increases of up to 500%, 227%, and 248% compared to untreated cells. However, Nocodazole and Taxol decreased invasion into Caco-2 cells, with only E. coli K1 showing an increase of about 150% in Taxol-treated cells. The findings with eukaryotic cytoskeleton inhibitors on neonatal H4 cells suggest that bacterial invasion mainly relies on microfilaments or microfilament-dependent. No specific dependence on the cytoskeleton was seen in Caco-2 cells. In conclusion, cytoskeletal inhibitors significantly affected bacterial invasion, specifically Cronobacter, compared to untreated cells. This suggests that invasion methods may vary by strain and are influenced by how each inhibitor alters cytoskeleton behavior. Therefore, the invasion process, both with and without cytoskeletal inhibitors, is crucial for understanding how bacteria manipulate cell components during infection. Full article

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic that inhibits bacterial protein synthesis through binding to ribosomal RNA, also preventing the assembly of the initiation complex during translation. It is one of the last-line therapeutic options for serious infections caused by problematic Gram-positive pathogens, including vancomycin-resistant and multidrug-resistant Enterococcus species. Data from recent large-scale studies show a 2.5-fold increase in the prevalence of clinical LNZ-resistant enterococci (LRE) over the past decade with a global detection rate of 1.1% for LNZ-resistant E. faecium (LREfm) and 2.2% for LNZ-resistant E. faecalis (LREfs). Most reported cases have originated from China, followed by South Korea and the United States. LREfm typically belongs to the high-risk clonal complex 17, whereas LREfs demonstrates a heterogeneous population structure. Mutations in the 23S rRNA and ribosomal proteins, as well as acquired resistance genes such as cfr, optrA, and poxtA are involved in the development of LNZ resistance among enterococci. Whole-genome sequencing (WGS) has been recognized as a gold standard for identifying the underlying molecular mechanisms. It exposes that numerous LRE isolates possess multiple LNZ resistance determinants and mutations, further complicating the treatment strategies. The present review article summarizes all known mutational and non-mutational LNZ resistance mechanisms and presents a global overview of WGS-based studies with emphasis on resistome analysis of clinical LREfs and LREfm isolates published in the literature during the period 2014–2025. Full article

Brucella infection is associated with an increased risk of adverse obstetric outcomes in humans and animals. Decidualization, a process involving structural and functional changes in endometrial stromal cells, is essential for proper trophoblast implantation and placental development. Trophoblasts’ migration and their ability to invade the decidua and to undergo tubulogenesis, critical for proper implantation and placental development, are normally promoted by decidual cells. We evaluated whether Brucella infection of human endometrial stromal cells (T-HESC cell line) affects their ability to decidualize and to promote trophoblast functions. Infection of T-HESC cells with either B. abortus, B. suis, or B. melitensis resulted in deficient decidualization (as revealed by reduced prolactin levels) and an increased production of proinflammatory chemokines (C-X-C motif chemokine ligand 8 -CXCL8- and C-C motif chemokine ligand 2 -CCL2-) as compared to uninfected cells subjected to decidualization stimuli. In addition, conditioned media (CM) from infected decidualized T-HESC induced an inflammatory response (CXCL8, CCL2 and interleukin-6 -IL-6) in human trophoblasts (Swan-71 cell line) but reduced their ability to produce progesterone. Trophoblasts preincubated with this CM also had reduced migration, invasion, and tubulogenesis capacities, and this impairment was mediated, at least in part, by CXCL8 and CCL2. Moreover, infection of decidual stromal cells impaired the adhesion and spreading of blastocyst-like spheroids formed by Swan-71 cells. Brucella infection also affected the chemotactic capacity of decidual stromal cells for trophoblasts. Overall, these results suggest that Brucella infection of endometrial stromal cells impairs key processes required for successful implantation and placental development. Full article