Search Results (2,926)

Background/Objectives: Multidrug-resistant (MDR) Enterobacter spp. are critical pathogens within the ESKAPE group, frequently exhibiting resistance to carbapenems. Antimicrobial photodynamic therapy (aPDT) represents a promising non-antibiotic strategy to circumvent these resistance mechanisms. This scoping review aims to map the current evidence regarding the efficacy of aPDT in inactivating Enterobacter spp., identifying the most effective photosensitizers (PS), light parameters, and existing research gaps. Methods: A systematic search was performed across PubMed, Scopus, and Google Scholar (2013–2025) following PRISMA-ScR guidelines and registered on OSF. Studies were included if they evaluated aPDT against Enterobacter spp. (in vitro or in vivo) and provided quantitative data on microbial reduction. Data was extracted using a standardized charting form covering bacterial strains, PS type, light source, and viability reduction. The results from the eligible sources of evidence were synthesized narratively to address the review objectives. Results: Despite the clinical priority of Enterobacter, only seven studies met the eligibility criteria. Methylene Blue remains the most frequently studied PS, achieving reductions of 3–8 log₁₀. Emerging evidence highlights the synergistic efficacy of monocationic chlorins and graphene-based nanomaterials in enhancing the bactericidal effect of light-based treatments. Notably, aPDT demonstrated the ability to inactivate carbapenemases, the bacterial enzymes responsible for carbapenem resistance. However, only two studies evaluated in vivo applications, primarily within dental settings. Conclusions: aPDT is a promising method against MDR Enterobacter spp. and bypasses traditional resistance mechanisms. However, the limited number of studies indicates a significant knowledge gap. Future research should focus on standardized in vivo protocols and the synergy between aPDT and conventional antibiotics to support clinical translation. Full article

Linezolid represents a critical last-resort treatment for severe multidrug-resistant (MDR) Gram-positive bacterial infections. Rising linezolid resistance in Enterococcus isolates threatens its efficacy; this study characterized the molecular features and transfer potential of plasmid-encoded linezolid resistance genes optrA and poxtA in a linezolid-resistant Enterococcus asini isolate from chickens. An E. asini strain was isolated during a surveillance program focusing on drug-resistant Gram-positive bacteria in poultry. PCR screened linezolid resistance genes, conjugation and plasmid stability assays evaluated gene transferability and stability, and whole-genome sequencing (WGS) was performed using both the Illumina and Nanopore platforms. We present the first detection of optrA and poxtA genes in E. asini recovered from chicken feces in China. Sequence analysis of the complete genome showed that poxtA and optrA were situated on two distinct plasmids. The poxtA positive plasmid, pHNGXN23C145Ea-1, also carried multiple resistance genes, including tet(S), fexB, erm(B), ant(6)-Ia, aph(3′)-III. Furthermore, the poxtA gene was flanked by IS1216E mobile elements. The optrA bearing plasmid, pHNGXN23C145Ea-2, harbours a common genetic array of ‘IS1216E fexA-optrA-erm(A)-IS1216E’. Conjugation experiments indicated that neither the poxtA- nor the optrA-bearing plasmid was transferred to recipient strains, which was consistent with sequence analysis showing that both plasmids lacked intact conjugative transfer regions. Stability assays confirmed that poxtA and optrA remained highly stable in the absence of selective pressure. Notably, this discovery was made in a livestock sample, despite the non-use of linezolid in food animals, suggesting that such niches may act as silent reservoirs for resistance genes, which could persist and potentially transfer to clinically relevant MDR pathogens. Full article

Background: Eravaycline is a novel fully synthetic fluorocycline that is currently approved for complicated intra-abdominal infections. However, it is sometimes also used off-label in tertiary care centers for other infection sites as an antibiotic of last resort due to its broad spectrum of activity and efficacy against Enterobacterales, including multidrug-resistant pathogens like extended spectrum β-lactamase (ESBL) producers or carbapenem-resistant Enterobacterales, as well as all Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin- and linezolid-resistant Enterococcus faecium (VRE). Methods: We retrospectively included a total of 78 patients from Austria and Udine who received eravacycline between April 2023 and August 2024 to evaluate the real-world efficacy of eravacycline in various infection sites and pathogens using descriptive statistics. Results: Eravacycline was most commonly used in intra-abdominal infections (44.9%), followed by pneumonia (12.8%) and infections of unknown origin (7.7%). Escherichia coli, including ESBL producers, was the most common pathogen (24.4%), followed by Enterococcus spp. (12.8%) and Klebsiella pneumoniae (12.8%). Clinical cure was achieved in 65% of patients, whereas microbiological cure was documented in 46%; source control was attained in 48.7%, and 16.7% died within 30 days. A total of 48% of patients required intensive care. Conclusions: Eravacycline represents a possible therapeutic option for a wide range of pathogens, but its use must be evaluated in the context of infection site and severity. Full article

Candida albicans (C. albicans) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly under conditions of dysbiosis or immunosuppression. Treatment remains challenging due to increasing multidrug resistance. This study investigates the in vitro antifungal potential of Viroelixir, a standardized polyphenol blend derived from green tea and pomegranate and enriched in catechins (including epigallocatechin gallate, EGCG), ellagitannins (notably punicalagin), ellagic acid, and flavonoids, with particular focus on its potential anti-virulence mechanisms. Methods: The effect of Viroelixir on C. albicans growth was assessed using MTT assay, optical density measurements, colony formation, carbohydrate quantification, and pH variation analysis. Biofilm formation, morphological transition, ROS production, necrosis, virulence gene expression, adhesion, and host immune responses were also evaluated. Results: Viroelixir significantly inhibited C. albicans growth and reduced colony formation compared with untreated controls. The formulation also inhibited biofilm formation and markedly reduced pseudohyphal development, reaching up to 94% reduction under specific treatment conditions. Flow cytometry analysis showed an increase in dead fungal cells, reaching approximately 88% following exposure to Viroelixir at the highest tested concentration. In addition, Viroelixir reduced the transcript levels of several virulence-associated genes, including SAP1–SAP9 and EAP1. In epithelial cell co-culture models, pre-treatment of C. albicans with Viroelixir reduced fungal adhesion and attenuated epithelial inflammatory responses, including IL-6, IL-8, and hBD-2 production, and was associated with reduced activation of the TLR4-NF-κB signaling pathway. Conclusions: These findings suggest that the antifungal and anti-virulence effects observed may be associated with the polyphenolic compounds present in the Viroelixir formulation, highlighting its potential as a promising in vitro antifungal candidate against C. albicans. Full article

Microplastics (MPs) and metals frequently co-occur in aquatic environments, yet their combined effects on gut health and antimicrobial resistance in fish remain poorly understood. This study investigated the chronic effects of polyethylene (PE) and polystyrene (PS) microplastics, alone or combined with copper (Cu), on intestinal integrity, the gut-associated Gram-negative cultivable fraction, and phenotypic antimicrobial resistance in adult zebrafish (Danio rerio). Fish were exposed for 21 days to MPs (1 mg/L), Cu (25 µg/L), or their combinations. Histopathological analysis revealed that Cu-containing treatments induced more severe intestinal alterations, including edema, villus degeneration, and necrosis, whereas MPs-only exposures produced milder and heterogeneous responses. The composition of the Gram-negative cultivable fraction varied among treatments, with Cu, particularly in combination with MPs, associated with a broader occurrence of opportunistic and potentially pathogenic taxa. Antimicrobial susceptibility testing showed a high prevalence of multidrug resistance across treatments, with broader resistance spectra observed in Cu-containing exposures, consistent with metal-driven co-selection. In contrast, MPs alone did not systematically increase resistance and, for some antibiotics, showed resistance levels comparable to or lower than controls. Integrated multivariate analyses indicated that intestinal pathology and antimicrobial resistance co-varied along gradients of overall stress severity and stressor type, with Cu acting as the dominant driver and MPs exerting a modulatory, context-dependent influence. Overall, these findings highlight the importance of integrated assessments of gut pathology, microbial composition, and antimicrobial resistance to better understand the ecological and One Health implications of combined microplastic–metal exposure in aquatic systems. Full article

Avian infective endocarditis is an uncommon but severe disease that is typically diagnosed postmortem because of nonspecific clinical signs and rapid progression. In the present study, five broiler chickens (n = 5) from a commercial flock were examined with septicemia and lesions suggestive of endocarditis. This study reports the first molecularly confirmed and characterized case of valvular endocarditis associated with multidrug-resistant Vagococcus fluvialis in poultry and provides a comprehensive review of bacterial endocarditis in avian species. The case involved a broiler chicken that presented with sudden death and septicemic lesions, including vegetative valvular endocarditis, pericarditis, and multiorgan involvement. Bacterial isolates recovered from cardiac lesions were identified as V. fluvialis using MALDI-TOF mass spectrometry and confirmed by 16S rRNA gene sequencing. Antimicrobial susceptibility testing revealed a multidrug resistance profile, with resistance to several antimicrobial classes commonly used in poultry production. The literature review identified published studies describing avian infective endocarditis, which predominantly affects poultry and is caused mainly by Gram-positive bacteria, with clinical signs and necropsy findings largely overlapping across etiologies. These findings highlight the novelty of V. fluvialis as a potential etiological agent of avian infective endocarditis and underscores the diagnostic challenges associated with avian endocarditis, particularly when uncommon pathogens are involved, and underscore the importance of advanced identification methods for an accurate etiological determination. Collectively, the results of this study expand the spectrum of bacterial species associated with avian infective endocarditis and emphasize the relevance of antimicrobial resistance and improved diagnostic strategies in poultry health and disease surveillance. Full article

Antimicrobial resistance (AMR) represents a global health crisis, driven largely by the mobility of resistance determinants through mobile genetic elements (MGEs). These include plasmids, integrons, insertion sequences, transposons, integrative and conjugative elements (ICEs), and prophages, which together facilitate horizontal gene transfer (HGT) across bacterial species and ecosystems. This review aims to provide a comprehensive synthesis of current knowledge on the types, mechanisms, ecological drivers, and impacts of MGEs in the dissemination of antibiotic resistance genes (ARGs). Methods involved critical evaluation of recent genomic, epidemiological, and ecological studies, alongside case studies of clinically significant resistance outbreaks. Findings highlight how MGEs function as hubs for ARG capture, recombination, and stabilization, enabling the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. We also explored their interactions with ecological pressures such as antibiotics, heavy metals, and biocides, as well as their role in One Health transmission pathways. The significance of this study lies in linking molecular insights with applied strategies, including genomic surveillance, MGE-targeted inhibitors, phage therapy, and CRISPR-based interventions. Understanding MGEs is essential for designing effective interventions to mitigate AMR and protect global health. Full article

Background: Long-bone non-unions complicated by osteomyelitis remain a major reconstructive and healthcare challenge, particularly in resource-limited settings with a high prevalence of multidrug-resistant (MDR) pathogens. Conventional staged management is associated with a prolonged treatment burden, repeated procedures, and delayed functional recovery. This study evaluated the clinical, radiological, functional, and short-term safety outcomes of a single-stage approach using custom-threaded antibiotic-coated locking nails (TACLNs) in a high-resistance cohort. Methods: This prospective single-center cohort study enrolled 30 adults with osteomyelitis-associated femoral or tibial nonunion at a tertiary hospital in Peshawar, Pakistan. All patients underwent radical debridement and single-stage stabilization with a chest tube mold TACLN loaded with vancomycin and gentamicin, with culture-directed adjunctive antibiotics for resistant organisms. Outcomes were assessed at baseline, Weeks 3 and 6, and Month 6 using inflammatory markers, RUST score, VAS pain, EQ-5D-5L, ASAMI criteria, and return to work or usual activity. No formal sample size calculation was performed, and this study was exploratory in nature. Results: The cohort (mean age 44.9 ± 9.9 years) had a challenging microbiological profile, with 40.0% MDR and 13.3% extensively drug-resistant (XDR) infections. By Month 6, short-term infection control was achieved in 96.7% of patients, with significant reductions in ESR and CRP (both p < 0.001). Radiographic union was achieved in 90.0% of cases at a mean of 18.6 weeks, and the mean RUST score improved from 4.87 to 10.43 at the final follow-up. The VAS pain decreased from 5.23 at week 3 to 0.73 at month 6, EQ-5D-5L improved from 0.39 to 0.84, and 90.0% returned to work or usual activity by month 6. No cement debonding, implant failure, or nephrotoxicity was noted. Conclusions: In this single-arm exploratory cohort, TACLNs were associated with favorable short-term infection control, radiographic union, and functional recovery in osteomyelitis-associated long-bone nonunion, including in an MDR/XDR setting. The independent contribution of the threaded core design cannot be established. Larger multicenter comparative studies with longer follow-ups are needed to confirm the durability and implementation feasibility. Full article

Background/Objectives: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed to evaluate the effectiveness and safety of cefiderocol for the treatment of MDR-GNB infection. Methods: We conducted a retrospective observational study including all adult patients who received ≥72 h of cefiderocol between November 2020 and October 2024 at a Spanish tertiary-care hospital. The primary outcome was clinical success, defined as survival and absence of clinical recurrence 30 days after cefiderocol initiation. Secondary outcomes included 30- and 90-day mortality, clinical and microbiological recurrence, emergence of resistance, and adverse events. Results: Eighty patients were included (median age 64 years [IQR 56–72]; 81.3% male). Respiratory (26.2%) and abdominal (22.5%) infections were the most common, and 20% presented with bacteremia. At infection onset, 26.2% had septic shock and 45% required intensive care unit admission. The three most frequently isolated pathogen was Pseudomonas aeruginosa (33.9%), followed by Enterobacterales (33%) and Stenotrophomonas maltophilia (30.1%). Clinical success was achieved in 67.5% of patients. Thirty and 90-day mortality rates were 27.5% and 36.5%, respectively. Recurrence within 90 days occurred in 5% of cases. Emergence of resistance was detected in one Klebsiella pneumoniae ST147 isolate, and serious adverse events occurred in 5% of patients. Conclusions: In a cohort including a substantial proportion of critically ill patients, cefiderocol was associated with favorable clinical outcomes and an acceptable safety profile. These findings suggest that cefiderocol may represent a useful therapeutic option for severe MDR-GNB infections in patients with limited treatment alternatives. Full article

The increase in multidrug resistance in microorganisms and the rise of emergent infectious diseases worldwide is a threat to human and animal health. Therefore, research on new molecules with antibiotic potential is a priority. Lichens have a unique secondary metabolism with relatively untapped potential, yet their essential oils (EOs) and volatile organic compounds (VOCs) remain a relatively untapped resource. This systematic review was conducted following PRISMA 2020 guidelines, with a comprehensive search performed in the Web of Science database for studies published up to 2023. From 254 identified records, six studies involving nine lichen species (Evernia prunastri, Evernia divaricata, Cladonia rangiformis, Cladonia furcata, Parmotrema perlatum, Lichina pygmaea, Parmelia perlata, Hypogymnia physodes, and Parmelia sulcata) met the eligibility criteria. The synthesized data show that these volatile fractions possess significant antimicrobial potential, with minimum inhibitory concentrations (MICs) generally lower than 1 mg/mL. Major bioactive constituents identified include atraric acid, orsellinates, and various sesquiterpenes. While the current evidence highlights a strong potential of lichen volatiles against pathogens, research is limited to a small fraction of known species. This review identifies a critical gap in testing these compounds directly against MDR clinical isolates and suggests that future research should focus on high-biomass species and the heterologous expression of lichen biosynthetic genes to develop sustainable antimicrobial applications. Full article

Neonatal meningitis-associated Escherichia coli (NMEC) is a formidable pathogen in veterinary medicine. The emergence of atypical, multidrug-resistant (MDR) variants complicates disease control. An Escherichia coli (E. coli) strain was isolated from the brain tissue of a deceased calf with acute meningitis. Comprehensive characterizations were performed, including whole-genome sequencing (WGS), multi-locus sequence typing (MLST), antimicrobial susceptibility testing (AST), murine pathogenicity assays, and RT-qPCR evaluation of neuroinflammatory cytokines. Results: The isolate (O18ab:H14) was identified as a capsule-deficient NMEC strain belonging to phylogroup A and sequence type ST1434. WGS showed that the genome size of this strain is 5.1 Mb, containing 73 strictly defined antimicrobial resistance genes and 202 virulence factors. These may be involved in the compensatory mechanism for capsule deficiency, and further functional verification is required. Phenotypically, it exhibited a robust MDR profile. In the murine model, the strain demonstrated high lethality, and induced severe multi-organ lesions characteristic of both meningitis and systemic sepsis. While intraperitoneal injection bypasses natural colonization routes, the brain-specific bacterial persistence and neuronal pathology imply neurotropic potential. Furthermore, RT-qPCR confirmed a severe neuroinflammatory response, marked by the significant upregulation of IL-1β, IL-6, and TNF-α in the infected brains. This study characterizes a novel, highly virulent, and MDR capsule-deficient NMEC/SEPEC hybrid strain. The findings emphasize the urgent need for continuous genomic surveillance of atypical E. coli pathotypes in livestock. Full article

Background/Objectives: Immunocompromised children undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic disorders face a high risk of serious, life-threatening infections caused by multidrug-resistant (MDR) bacteria. Cefiderocol is a novel siderophore cephalosporin, indicated for use in adult patients with MDR Gram-negative infections. Clinical data in immunocompromised children are limited. To report a multicenter real-life experience from the Infection Working Group of the Italian Pediatric Hematology and Oncology Association (IWG-AIEOP) on the use of cefiderocol in treating pediatric onco-hematologic patients with severe, high-risk infections. Methods: Multicenter retrospective collection of infectious episodes treated with cefiderocol, from January 2021 to December 2024, in patients 18 years or younger, after treatment for malignancies or undergoing HSCT in the AIEOP network, part of a prospective, observational study on the etiology and outcome of febrile episodes among 24 AIEOP centers (code NCT06419426). Results: Fifteen episodes of MDR, life-threatening Gram-negative infections treated with cefiderocol in 13 pediatric onco-hematologic patients were collected. There were eight males and five females, mainly affected by acute leukemia (six lymphoblastic and four myeloid, three other hematologic malignancies). The median age was 11.1 years (range 1–17.4 years), and the median weight was 37.8 kg (range 8–65). Bloodstream infection occurred in 10 of 15 episodes. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Stenotrophomonas maltophilia were isolated in 11, 3, and 1 episodes, respectively. Notably, 11 of 15 isolated pathogens carried a metallo-beta-lactamase (MBL) gene (Verona integron-encoded, VIM, n = 10; New Delhi, NDM, n = 1). All patients achieved infection resolution and were alive and infection-free 90 days after infection onset. Conclusions: Cefiderocol was well tolerated and showed encouraging, favorable clinical outcomes, without serious adverse effects. Full article

The escalating prevalence of antimicrobial resistance (AMR) in Gram-negative uropathogens represents a critical bottleneck in global clinical management. This study evaluated shifting resistance phenotypes and patient risk profiles to identify independent predictors of multidrug resistance (MDR). A comprehensive retrospective analysis was conducted on a cohort of 318 patients, utilizing statistical modeling to evaluate the impact of demographics, prolonged hospitalization, and comorbidities on MDR. Findings revealed a significant longitudinal exacerbation of resistance since 2012. A majority of Klebsiella pneumoniae strains and nearly all Myroides and Providencia species exhibited high-level resistance to cephalosporin/beta-lactamase inhibitor combinations. While high-dose piperacillin-tazobactam remains a therapeutic alternative, its utility is increasingly constrained by escalating Minimum Inhibitory Concentrations (MICs) for Klebsiella and Escherichia coli (E. coli). Statistical modeling identified advanced age as the primary independent driver, with MDR risk increasing linearly with every additional year of age. Furthermore, indwelling catheterization was strongly associated with resistant infections, while human immunodeficiency virus (HIV) status emerged as a significant cofactor in the selection of highly resistant strains. These findings underscore the need for a critical recalibration of therapeutic frameworks, prioritizing precision-guided stewardship. Pharmacodynamic optimization, through extended or continuous infusion regimens and individualized loading doses, is essential to mitigate the clinical burden of resistant pathogens within vulnerable geriatric cohorts. Full article

Carbapenems comprise a class of β-lactam antibiotics with broad-spectrum hydrolytic activity and are often reserved as last-line agents for the treatment of serious multidrug-resistant (MDR) bacterial infections. Clinically important nosocomial MDR Gram-negative bacteria (GNB) include Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Carbapenem resistance among these organisms is predominantly mediated by the production of β-lactamases called carbapenemases, such as K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and selected oxacillinase (OXA)-type carbapenemases. These enzymes degrade carbapenems, significantly compromising their clinical efficacy. To address escalating antimicrobial resistance, novel next-generation β-lactamase inhibitors (BLIs), partnered with established β-lactams (BLs), have been approved or are currently under development to inhibit carbapenemase activity. The present narrative review aims to synthesize the most current information on the major carbapenemases and discusses recently approved and investigational BL/BLI combination therapies in terms of their mechanisms of action, spectrum of activity, gaps in coverage, and available clinical and in vitro evidence. Development of resistance to novel BL/BLI combinations is also examined. Comparative analysis of inhibitory spectra and microbiological coverage indicates a continued need for metallo-β-lactamase inhibitors with direct pan-inhibitory activity, pathogen-specific BL/BLI regimens for carbapenem-resistant A. baumannii, and carbapenemase-targeted agents effective in the context of non-enzymatic resistance mechanisms. Treatment-emergent resistance to novel BL/BLIs and limitations in activity profiles underscore the critical need for continued innovation in pipeline development, vigilant global and local surveillance of carbapenemase epidemiology, and robust antimicrobial stewardship strategies to aid in preserving the efficacy of the antibacterial drug armamentarium. Full article

Background/Objectives: Developing novel strategies to combat respiratory infections caused by multidrug-resistant “priority pathogens” like the ESKAPEE Pseudomonas aeruginosa and Staphylococcus aureus is an urgent priority. Methods: We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). Evaluation included MIC assays against laboratory and clinical multidrug-resistant isolates, mechanistic studies of membrane permeabilization, cytotoxicity testing on BEAS-2B bronchial epithelial cells, and proteolytic stability assays in human elastase and sputum. Results: Despite their reduced size, lower positive charge, and decreased proline content, both variants retained full antimicrobial activity against clinical pathogens with consistent MIC values ≤ 25 µM. These variants exhibit membrane permeabilization in P. aeruginosa but may also relay on a hybrid mode of action involving also intracellular targets. Notably, B7-006 and B7-007 displayed low cytotoxicity compared to the lytic peptide BMAP-18. While B7-007 showed greater susceptibility to proteolytic degradation than its parent B7-005, it preserved partial integrity during the initial hours of exposure. Conclusions: Overall, these findings demonstrate that the B7 scaffold tolerates substantial truncation while preserving potency and selectivity, identifying a minimal 13-amino-acid active core. This work provides critical insights into structure–activity relationships and supports the development of compact, mechanistically versatile antimicrobial peptides to address the growing threat of multidrug-resistant respiratory pathogens. Full article