bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–05–03
38 papers selected by
Luca Bolliger, lxBio
  1. Spot-on phage therapy: stable formulations, smarter dosing for topical phage application.
  2. Phenotypic heterogeneity shapes phage resistance and cocktail efficacy in Klebsiella pneumoniae.
  3. Sequential Phage Delivery Can Outperform Cocktails by Delaying Cross-Resistance Evolution.
  4. The Joint Action of Bacteriophage and Antibiotics in the Treatment of Staphylococcus aureus infections in Galleria mellonella.
  5. Breaking the cycle of hard-to-heal wounds: the role of autologous whole blood clot therapy.
  6. Modelling the Role of Phages in Biofilm Ecosystems and the Spread of Antimicrobial Resistance.
  7. Phages for One Health: regulatory and product life cycle considerations.
  8. Combating Pseudomonas aeruginosa biofilms: Pathogenesis, resistance mechanisms and novel treatment approaches in an era of emerging antimicrobial resistance.
  9. The WHO priority list of antibiotic-resistant bacteria: challenges and opportunities for next-generation antimicrobial development.
  10. What is the impact of the virome and mycobiome on female reproductive tract health? A systematic scoping review.
  11. French adaptation of Wound Hygiene in the management of pressure injuries: recommendations from SFE experts.
  12. Targeting Bacterial Infections in Periodontal Disease: From Conventional Antibiotics to Next-Generation Therapeutics.
  13. Harnessing the oral microbiome in chronic liver disease: mechanisms, therapeutic modulation and translational frontiers.
  14. Characterization of Klebsiella Phages Isolated Against a Clinical Host with High Genome and Proteome Identity but Variable Tail Fibers.
  15. Isolation and Characterization of Lytic Bacteriophages against Antibiotic-Resistant Klebsiella Pneumoniae from Wastewater Samples.
  16. Multidrug-Resistant Serratia fonticola Causing Diabetic Foot Infection: A Rare Case Highlighting Emerging Antimicrobial Resistance.
  17. Microbiome and its role in bronchiectasis.
  18. Detection to Disruption: A Comprehensive Review of Bacterial Biofilms and Therapeutic Advances.
  19. Synergistic effects of halo-plaque forming phage cocktails against polymicrobial Acinetobacter baumannii and Staphylococcus aureus.
  20. Acinetobacter baumannii: Mechanisms of antibiotic resistance, quorum sensing regulation, and current therapeutic strategies.
  21. From Sewage to Salvage: Complete Characterization of Arefeen1 Phage Against MDR Pseudomonas aeruginosa.
  22. Broad-spectrum phage cocktail targeting Campylobacter improves survival in Galleria mellonella, a bridging host model for poultry biocontrol.
  23. Reframing Periodontitis: A Concise Review of Shifting Paradigms and Contemporary Clinical Practice.
  24. Metagenome-based virome analysis identifies the oral viral signatures for periodontitis.
  25. Synergistic Roles of Fimbriae and Gingipain Genotypes in Porphyromonas gingivalis and Their Association With Periodontitis Severity.
  26. The Guild Model of CF Airway Microbial Ecology.
  27. Dental Pulp Stem Cells for the Management of Plaque Biofilm-Associated Infections : A Review.
  28. Candida Drug Resistance in Patients With Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.
  29. A Quarter-Century of Chronic Obstructive Pulmonary Disease in the Intensive Care Unit (2000-2025): A Bibliometric Roadmap of Thematic Evolution and Future Frontiers.
  30. Recent perspectives on precision-targeting therapy against oral biofilm.
  31. Enterococcus faecium colonization and persistence in a model of diabetic wound infection.
  32. A disrupted microbial network and an ecological shift towards anaerobes in NTM-infected cystic fibrosis patients.
  33. A State of Art Review: Volatile Organic Compounds and Periodontitis.
  34. Shared signals shape phages' lifestyles.
  35. Update to the management of recurrent urinary tract infections in women aged 16 years and older.
  36. The relationship between urinary albumin-to-creatinine ratio and bacterial profiles/inflammatory markers in diabetic foot infections: a retrospective cross-sectional observational study.
  37. Bacterial quantitation in clinical infection: a systematic review.
  38. Burn Infections and Sepsis: Challenges and Future Prospects of Antibacterial Therapy.
  1. Front Cell Infect Microbiol. 2026 ;16 1697070
    Spot-on phage therapy: stable formulations, smarter dosing for topical phage application.
    Jagnoor Singh Sandhu, Amrita Parida.
      The growing antimicrobial resistance crisis has led to renewed interest in bacteriophage therapy, mostly for topical uses such as wound/burn care. However, the clinical application of topical phage therapy is delayed due to a major problem that dosing and delivery protocols lack standardization. By gathering scattered published studies on topical phage therapy, this review attempts to bridge the most important gap. We unpack the complicated interactions between phage titer (most of the time 107-109 PFU/mL), multiplicity of infection (MOI), and the stability of various formulations such as hydrogels, creams, and polymer-based sprays, which are some of the factors that determine the effectiveness of the treatment to the greatest extent. Our review extends to the bacterial load and biofilm maturity, whose raising is the main explanation of why mature biofilms need higher, repeated dosing or a combination of antibiotics and depolymerase-armed phages to be treated effectively. Additionally, we collect pharmacokinetic/pharmacodynamic (PK/PD) essentials from animal experiments and talk about the role of wound dressings in the controlled delivery of phages. The authors argue that topical phage therapy can be most effective only when it is a combined effort: accurate dose calculation, intelligent formulation design, and careful planning of the time for application. To get from the laboratory to the clinic, the field needs to urgently implement standardized PK/PD frameworks, stringent stability testing, and comprehensive clinical trials. This paper brings together these components to serve as a practical guide in the development of efficient, dependable, and easily translatable topical phage treatment regimens.
    Keywords:  PK/PD; biofilms; formulation stability; moi; phage therapy; topical delivery
    DOI:  https://doi.org/10.3389/fcimb.2026.1697070
  2. Microbiol Spectr. 2026 Apr 30. e0226125
    Phenotypic heterogeneity shapes phage resistance and cocktail efficacy in Klebsiella pneumoniae.
    Lucas Mora-Quilis, Rafael Sanjuán, Pilar Domingo-Calap.
      The emergence of phage-resistant bacteria poses a significant challenge to the success of phage therapy. Although phage cocktails can delay resistance, their efficacy relies on the ability to target the full spectrum of resistant variants, which are often more diverse than those represented by clonal isolates. In this study, we investigated how phenotypic diversity within phage-resistant Klebsiella pneumoniae influences susceptibility to newly isolated phages, and the effectiveness of phage cocktails. We isolated phages using three cultures resistant to a capsule-dependent phage: a heterogeneous acapsular population, an acapsular mutant with a stable phenotype, and a capsule-reverted isolate that regained capsule expression upon removal of phage pressure. These phages differed in host tropism and in their capacity to delay resistance emergence when combined with the capsule-dependent phage. Phages targeting acapsular variants, particularly those isolated from the heterogeneous population, were the most effective, exhibiting strong synergy. Single-cell analyses further revealed that sustained selective pressure from the capsule-dependent phage prevents capsule reversion and maintains cocktail efficacy. Overall, our results highlight the importance of accounting for phenotypic heterogeneity when designing phage therapies, and support population-level approaches for optimizing phage cocktail composition.IMPORTANCEPhage therapy is a promising alternative to antibiotics, but its success is often limited by the rapid emergence of phage-resistant bacteria. These resistant populations can be highly heterogeneous, comprising both stable mutants and variants with reversible, non-genetic resistance. In this study, we explore how this phenotypic diversity influences the effectiveness of phage cocktails. By isolating new phages and testing them in combination, we demonstrate that the selective pressure exerted by specific phages can prevent the reversion in transiently resistant variants, thereby sustaining treatment efficacy. Our findings highlight the need to consider not only the range of bacterial targets but also how phage pressure shapes bacterial population dynamics. This work offers a more refined strategy for designing phage cocktails with improved clinical potential.
    Keywords:  Klebsiella pneumoniae; capsule reversion; phage cocktail; phage resistance; phenotypic heterogeneity
    DOI:  https://doi.org/10.1128/spectrum.02261-25
  3. Viruses. 2026 Mar 25. pii: 404. [Epub ahead of print]18(4):
    Sequential Phage Delivery Can Outperform Cocktails by Delaying Cross-Resistance Evolution.
    Elizabeth C Stuart, Justin R Meyer.
      Antimicrobial resistance has renewed interest in bacteriophage therapy, yet bacterial evolution frequently undermines treatment efficacy. Combination phage therapy is commonly implemented as simultaneous phage cocktails, but whether this is optimal remains in question. Here, we experimentally compared simultaneous versus sequential administration of two phages, an evolved λ called 'λtrn' and T2, on Escherichia coli K-12 under controlled laboratory conditions. Across replicated experiments, treatment outcome depended strongly on delivery strategy, dosing order, and timing. Contrary to expectations, sequential delivery consistently achieved greater and more sustained bacterial suppression than simultaneous cocktails, although only when T2 initiated the sequence. Phenotypic assays revealed that treatment differences were driven by the accessibility and timing of cross-resistance evolution. λ-first treatments rapidly selected for cross-resistant bacteria prior to exposure to the second phage, rendering subsequent treatment ineffective. In contrast, T2-first sequential treatments delayed or limited cross-resistance and frequently produced single-phage resistance or collateral sensitivity. Cocktail treatments showed intermediate dynamics, with cross-resistance evolving more slowly but consistently. Whole genome sequencing identified distinct genetic routes to cross-resistance, including regulatory mutations in envZ affecting expression of the phage receptor OmpF, as well as envelope-modifying, mucoidy-associated mutations. Engineering envZ mutations into unevolved backgrounds confirmed the mutation's sufficiency to confer low-cost cross-resistance. Together, these results demonstrated that phage therapy efficacy depended not only on phage composition but on how selection pressures were ordered in time, highlighting evolutionary steering as a powerful principle for multi-phage therapy design.
    Keywords:  Escherichia coli; bacteriophage therapy; cross-resistance; experimental evolution; phage cocktails; resistance evolution; sequential delivery
    DOI:  https://doi.org/10.3390/v18040404
  4. bioRxiv. 2026 Apr 13. pii: 2026.04.13.718207. [Epub ahead of print]
    The Joint Action of Bacteriophage and Antibiotics in the Treatment of Staphylococcus aureus infections in Galleria mellonella.
    Brandon A Berryhill, Teresa Gil-Gil.
      Given the global rise of antibiotic resistance, there has been a resurgence of interest in bacteriophage therapy, typically administered concomitantly with antibiotics and currently used as a last resort treatment. In this study, we use the Galleria mellonella model to investigate the treatment outcomes and dynamics of joint therapy against a toxigenic and pathogenic strain of Staphylococcus aureus . While our previous research demonstrated that single-agent therapy, whether using bactericidal or bacteriostatic antibiotics or lytic phage, could suppress infections below a critical threshold, it rarely achieved complete bacterial eradication. Here, we show that the coadministration of a phage PYO Sa with antibiotics generally enhances clearance, regardless of the antibiotic class. Joint therapy with daptomycin resulted in the complete clearance of infecting bacteria in the majority of larvae. Notably, even when combined with ampicillin, to which the bacteria are highly resistant, approximately half of the larvae achieved infection clearance. Taken together, these results demonstrate that joint therapy with phage and antibiotics enhances clearance beyond what either agent achieves alone, while underscoring that treatment timing and drug-specific pharmacodynamics remain critical determinants of therapeutic outcome.
    Significance Statement: The global rise of antibiotic resistance has renewed interest in bacteriophage therapy, which is almost universally administered concomitantly with antibiotics in clinical practice. Using Galleria mellonella (the wax moth larvae), which possess an innate immune response functionally similar to that of mammals, we demonstrate that coadministration of bacteriophages and antibiotics significantly enhances infection clearance compared with single-agent therapies. Critically, this joint action of antibiotics and phage can achieve bacterial eradication even when employing antibiotics to which the bacteria are resistant. We also find that therapeutic efficacy is sensitive to treatment timing and the specific pharmacodynamics of each drug. These factors are not captured by standard in vitro assessments of antimicrobial activity. Together, these results motivate further quantitative study of clinically relevant dosing regimens to determine the impact of host-pathogen-drug interactions on treatment outcome.
    DOI:  https://doi.org/10.64898/2026.04.13.718207
  5. J Wound Care. 2026 May 02. 35(5): 409-415
    Breaking the cycle of hard-to-heal wounds: the role of autologous whole blood clot therapy.
    Robert J Snyder.
      Hard-to-heal (chronic) wounds pose significant challenges in healthcare due to their prolonged inflammatory phase and impaired healing processes. These wounds, commonly associated with diabetes, vascular insufficiency or impaired mobility, fail to progress through the orderly phases of haemostasis, inflammation, proliferation and remodelling. Persistent inflammation, driven by M1 macrophages, neutrophils and proteases, disrupts extracellular matrix (ECM) reconstruction and degrades growth factors and cytokines, halting healing. Conventional treatments often fail to address the underlying pathophysiology, prompting interest in advanced autologous therapies. Autologous whole blood clot (AWBC), an innovative autologous therapy, activates the patient's blood to create a biological scaffold rich in growth factors and cytokines. This scaffold promotes wound healing by supporting ECM reconstruction, causing inflammatory M1 macrophages to transition to regenerative M2 macrophages, and enhancing neutrophil clearance. The objective of this review was to summarise the current clinical evidence and elucidate the proposed biological mechanisms by which AWBC promotes healing in hard-to-heal wounds. Clinical studies have demonstrated AWBC's efficacy across multiple wound types, including diabetic foot ulcers, pressure ulcers and surgical wounds. With a robust safety profile, minimal risk of adverse reactions and reported efficacy, AWBC offers a transformative solution for hard-to-heal wound management, addressing unmet clinical needs and improving patient outcomes.
    Keywords:  autologous whole blood clot; chronic wounds; extracellular matrix; hard-to-heal wounds; therapeutic; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0325
  6. J Theor Biol. 2026 Apr 28. pii: S0022-5193(26)00117-7. [Epub ahead of print] 112492
    Modelling the Role of Phages in Biofilm Ecosystems and the Spread of Antimicrobial Resistance.
    Julien Vincent, Alberto Tenore, Maria Rosaria Mattei, Luigi Frunzo.
      The spread and control of antibiotic resistance is a major public health issue and challenge to address. This has driven a growing interest in bacteriophages, used alone or in combination with antibiotics to treat antibiotic-resistant biofilms. Evaluating the potential of phage therapy requires a detailed understanding of phages-microbes interactions, from their lytic activity to their capacity for transducing resistance genes. Mathematical models are a powerful tool to investigate specific aspects of these complex mechanisms, where a great number of biotic and abiotic interactions are involved. We present here a mathematical model exploring the role of phages in biofilm ecosystems and the potential of phage therapy to eliminate resistant bacterial populations. The model is formulated as a system of non-local partial differential equations in a one-dimensional, free-boundary domain. It incorporates all major routes of horizontal gene transfer - conjugation, natural transformation, and generalised transduction - along with selective pressure from metals and antibiotics, within a spatially structured, growing biofilm. Numerical simulations investigate the contribution of vertical and horizontal gene transfer, including generalised transduction, to the spread of plasmid-mediated resistance. We assess the potential of phage therapy, both as a stand-alone treatment and in combination with antibiotics, highlighting how phage-antibiotic synergy can substantially reduce the antibiotic concentration required to eradicate even resistant biofilms. The simulations reveal how phage predation contributes to selective pressure and shapes biofilm ecology.
    Keywords:  Antimicrobial resistance; Bacteriophage; Biofilm modelling; Horizontal gene transfer; Nonlocal PDEs; Transduction
    DOI:  https://doi.org/10.1016/j.jtbi.2026.112492
  7. Microbiology (Reading). 2026 Apr;172(4):
    Phages for One Health: regulatory and product life cycle considerations.
    Liberty Duignan, Evelien M Adriaenssens, Rosanna C T Wright, Annette Sansom, Ian MacLeod, Tobi E Nagel, Joshua D Jones, Joanne L Fothergill, Carmen H Coxon.
      There is growing interest in bacteriophage (phage) technologies across the One Health spectrum. The UK Parliament's Science, Technology and Innovation Select Committee recently published the results of its inquiry into 'the antimicrobial potential of bacteriophages' with recommendations on clarity on regulatory matters to support research and innovation. Products developed for different sectors will have different regulatory requirements. Here, we discuss how phage technology is applied across human, veterinary and food sectors, highlighting key regulatory considerations and the technical challenges that must be addressed to assure the quality, safety and efficacy of phage products. We also highlight the potential impact of phages in areas where they are most needed (low- and middle-income countries).
    Keywords:  One Health; bacteriophage; food; regulation; therapeutics; veterinary
    DOI:  https://doi.org/10.1099/mic.0.001626
  8. J Biomed Res. 2026 Apr 25. 1-16
    Combating Pseudomonas aeruginosa biofilms: Pathogenesis, resistance mechanisms and novel treatment approaches in an era of emerging antimicrobial resistance.
    Sachin Kumar Sharma, Tsering Yangzom, Dhruva Kumar Sharma.
      Biofilms are complex associations of microorganisms that are adhere to both biotic surfaces ( e.g., living tissues) and abiotic surfaces ( e.g., medical implants). These microorganisms, embedded in their own self-produced extracellular polymeric substance matrix, can be protected from unfavorable conditions. Among biofilm forming pathogens, Pseudomonas aeruginosa is an opportunistic bacteria associated with persistent and chronic infections due to its strong biofilm forming ability and high resistance to antibiotics. This paper focuses on P. aeruginosa biofilms, including the steps of biofilm development, their structural organization and genetic regulation, and the environmental factors affecting their survival. Biofilms exhibit significant resistance to conventional treatments, contributing to the persistence of chronic infections, implant-related infections, and non-healing wounds. The article discusses the diagnostic challenges and limitations of current antimicrobial treatment for P. aeruginosa biofilm associated infections. Recent approaches to improving clinical outcomes are also discussed, including the use of new antibiofilm compounds, mechanical solutions, and alternatives such as phage therapy, which integrate current knowledge of P. aeruginosa biofilm-related diseases to optimize therapeutic strategies for addressing antimicrobial resistance and improve patient outcomes.
    Keywords:  Pseudomonas aeruginosa; antimicrobial resistance; biofilms; cell communication; drug resistance; quorum sensing
    DOI:  https://doi.org/10.7555/JBR.39.20250484
  9. Front Pharmacol. 2026 ;17 1699987
    The WHO priority list of antibiotic-resistant bacteria: challenges and opportunities for next-generation antimicrobial development.
    Emad M Abdallah, Abdulrahman Mohammed Alhudhaibi, Mahmoud Dahab, Abdullah Al Noman, Pranab Dev Sharma, Tarek H Taha, Muhammad Nawaz.
      Antimicrobial resistance (AMR) remains one of the most serious global threats to public health, driven by the rapid emergence and dissemination of multidrug-resistant bacterial pathogens that compromise existing antibiotic therapies. In response, the World Health Organization (WHO) has defined priority lists of antibiotic-resistant bacteria to guide research, innovation, and drug development efforts. This narrative review synthesizes current knowledge on the molecular mechanisms underlying resistance in WHO-priority pathogens, including reduced membrane permeability, efflux pump overexpression, enzymatic drug inactivation, target modification, biofilm formation, and horizontal gene transfer. Beyond mechanistic insights, we critically evaluate the therapeutic limitations of conventional antibiotics, the failure of traditional discovery pipelines, and the growing clinical and economic burden of resistant infections. Emerging strategies, including artificial intelligence-assisted drug discovery, phage therapy, antimicrobial peptides, CRISPR-based systems, resistance-modifying combinations, and natural product-derived compounds and plant compounds, are assessed with emphasis on pharmacological feasibility, translational challenges, and clinical relevance. Particular attention is given to issues of delivery, toxicity, dosing optimization, resistance emergence, regulatory barriers, and real-world implementation. Finally, we highlight the central role of antimicrobial stewardship, surveillance, and a One Health framework integrating human, animal, and environmental sectors in mitigating resistance and sustaining therapeutic effectiveness. Collectively, this review underscores that addressing WHO-priority pathogens will require integrated, multidisciplinary strategies that bridge molecular biology, pharmacology, clinical translation, and public health.
    Keywords:  WHO priority pathogens; antibiotic resistance; antibiotics; drug discovery; health; infectious disease; novel antimicrobials
    DOI:  https://doi.org/10.3389/fphar.2026.1699987
  10. Front Immunol. 2026 ;17 1749584
    What is the impact of the virome and mycobiome on female reproductive tract health? A systematic scoping review.
    Ying Liu, Xingya Liao, Qimeng Chen, Hongyan Wang, Hualei Dai.
       Background: Traditional research on the female reproductive tract (FRT) microbiome has focused on the dominance of bacteria, particularly Lactobacillus, as a marker of health. This bacteriocentric paradigm, however, cannot fully explain clinical enigmas like the high recurrence of bacterial vaginosis (BV) or the persistence of HPV infection. This review introduces a new pan-microbiome framework that highlights the overlooked roles of the virome and mycobiome as the ecosystem's neglected components.
    Methods: We conducted a systematic scoping review following the PRISMA-ScR guidelines. We searched PubMed, Embase, and Web of Science databases for studies published up to October 2025. Inclusion criteria focused on original research and metagenomic studies examining the female reproductive tract (FRT) virome, mycobiome, and bacteriome, specifically their interactions and clinical associations with bacterial vaginosis (BV) and HPV persistence. Data were extracted and synthesized to evaluate the pan-microbiome framework.
    Results: The virome and mycobiome, despite their low biomass, are increasingly recognized as potential ecosystem modulators. Bacteriophages, for instance, are proposed to act as community "modulators," either through lytic cycles that maintain bacterial diversity or lysogenic cycles that may contribute to stabilizing pathogenic biofilms in dysbiosis like BV by introducing virulence genes. Similarly, fungi like Candida can transition from harmless commensals to pathogens when the protective bacterial balance is disturbed.
    Conclusion: FRT health is an emergent property of the complex interactions among bacteria, viruses, and fungi. A comprehensive understanding requires a pan-microbiome perspective. Future therapeutic strategies should move beyond a "one-bug, one-drug" approach toward "ecosystem restoration," using targeted methods like phage therapy or vaginal microbiota transplantation to attempt to restore the balance of the entire microbial community.
    Keywords:  bacterial vaginosis (BV); female reproductive tract microbiome; mycobiome; pan-microbiome; virome
    DOI:  https://doi.org/10.3389/fimmu.2026.1749584
  11. J Wound Care. 2026 May 02. 35(5): 355-364
    French adaptation of Wound Hygiene in the management of pressure injuries: recommendations from SFE experts.
    Pascal Serantoni-Vasseur, Martine Barateau, Lomig Le Bihan, Yann Groc.
      Pressure injuries (PIs) represent a major healthcare challenge due to their high prevalence, impact on quality of life, and associated clinical and economic burden. Delayed healing is frequently linked to the presence of biofilm, now recognised as a key barrier to wound resolution. The Wound Hygiene protocol, developed at an international level, proposes a structured approach to disrupt and prevent biofilm through early and repeated local interventions. This article presents the French adaptation of this protocol for the management of PIs, developed by experts from the Société Française de l'Escarre (SFE). The adapted framework integrates a comprehensive initial assessment followed by four key steps-cleansing; debridement; refashioning of the wound edges; and appropriate dressing selection-applied systematically throughout the care pathway. This approach promotes a proactive and standardised management of wounds, addressing both local and systemic factors that influence healing. By providing clinically relevant and context-specific guidance, this adaptation aims to support healthcare professionals in improving care practices, optimising healing outcomes, and reducing the burden associated with PIs.
    Keywords:  biofilm; chronic wounds; debridement; hard-to-heal wounds; pressure injury; pressure ulcer; wound; wound care; wound dressing; wound healing; wound hygiene
    DOI:  https://doi.org/10.12968/jowc.2026.0126
  12. Antibiotics (Basel). 2026 Apr 14. pii: 397. [Epub ahead of print]15(4):
    Targeting Bacterial Infections in Periodontal Disease: From Conventional Antibiotics to Next-Generation Therapeutics.
    Nada Tawfig Hashim, Rasha Babiker, Muhammed Mustahsen Rahman, Riham Mohammed, Vivek Padmanabhan, Md Sofiqul Islam, Mariam Elsheikh, Salma Musa Adam Abduljalil, Ghiath Mahmoud, Nallan C S K Chaitanya, Bogahawatte Samarakoon Mudiyanselage Samadarani Siriwardena, Ayman Ahmed, Bakri Gobara Gismalla.
      Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies.
    Keywords:  antimicrobial peptides; antimicrobial resistance; biofilms; host modulation; nanomedicine; periodontitis; pharmacogenomics; postbiotics; probiotics; quorum sensing inhibitors
    DOI:  https://doi.org/10.3390/antibiotics15040397
  13. J Hepatol. 2026 Apr 29. pii: S0168-8278(26)00226-6. [Epub ahead of print]
    Harnessing the oral microbiome in chronic liver disease: mechanisms, therapeutic modulation and translational frontiers.
    Chris Harlow, Merianne Mohamad, Jasmohan S Bajaj, Luigi Nibali, Avijit Banerjee, Vishal C Patel.
      Advanced chronic liver disease (ACLD) with cirrhosis is increasingly recognised as a condition shaped by the 'oral-gut-liver axis', in which dysbiosis within the oral microbiome contributes to systemic inflammation, infection, decompensation, and acute-on-chronic liver failure. Periodontal disease is highly prevalent in ACLD and is associated with endotoxaemia, immune dysfunction, and hepatic complications. The protected dental biofilm and keystone pathogens are key to the development of local and systemic inflammatory processes. The concept of "oralisation" of the gut microbiome further links oral dysbiosis to microbial translocation and hepatic injury. Recent advances in multi-omics, resistome profiling, and spatially resolved imaging have deepened insights into community function and host-microbial crosstalk, while salivary biomarker panels and microbial signatures across different aetiologies suggest potential tools for non-invasive diagnosis and risk stratification. Clinical priorities now lie along two paths which complement each other. The first is immediate implementation: embedding routine periodontal assessment and professional plaque removal within hepatology care; consistent advice on oral hygiene, fluoride use, diet, and smoking and alcohol cessation; careful review of proton-pump inhibitor use; and much closer coordination between hepatologists and dentists to facilitate indicated procedures. The second is innovation: development of precision microbiome-based interventional trials powered for hepatic outcomes, including targeted probiotics and postbiotics, biofilm-disrupting and quorum-quenching strategies, and phage or narrow-spectrum antimicrobial therapies supported by rapid diagnostics and robust antimicrobial stewardship. Integrating oral health into hepatology practice may represent a practical opportunity to reduce infection risk, delay decompensation, and improve survival and quality of life in people living with ACLD. This review aims to synthesise concepts around current understanding of the patho-biological mechanisms, analytical innovations, and therapeutic opportunities that define this evolving connection, as well as identify gaps in the knowledge base and propose avenues to harness and exploit the oral-gut-liver axis.
    Keywords:  antimicrobial stewardship; chronic liver disease; cirrhosis; dental biofilm; dysbiosis; multi-omics; oral microbiome; oral-gut-liver axis; periodontitis; resistome
    DOI:  https://doi.org/10.1016/j.jhep.2026.04.023
  14. Viruses. 2026 Apr 01. pii: 430. [Epub ahead of print]18(4):
    Characterization of Klebsiella Phages Isolated Against a Clinical Host with High Genome and Proteome Identity but Variable Tail Fibers.
    Jessica M Lewis, Daniel K Arens, Nathan R Zuniga, Julianne H Grose.
      The rate at which bacteria are gaining resistance to antibiotics is outpacing the discovery of new drugs. The rise of superbugs such as Carbapenem-resistant and Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae are leading to infections that are resistant to our last lines of defense. One of the most prolific genera of these bacteria is Klebsiella, which causes one third of Gram-negative infections. The need for alternative and companion treatments has never been greater. Bacteriophages are bacteria-infecting viruses with high specificity to their host. They show great promise as a potential treatment for antibiotic-resistant infections. Here, we describe the characterization of five closely related bacteriophages (ValerieMcCarty01-05) isolated against an antibiotic-resistant clinical strain of Klebsiella oxytoca, which is an emerging antimicrobial-resistant threat within the Klebsiella genus. These phages demonstrate high similarity at both the genomic and proteomic levels and share homology with other T4-like Enterobacterales phage. Two phages were further characterized through a mass spectrometry analysis of purified virions, identifying peptide spectrum matches for 40 proteins which appear to be virion proteins. In addition, the peptide spectrum matches for 39 hypothetical proteins suggest they are indeed proteins. Amino acid alignment revealed that the tail fibers display more variability than most of their genome, suggesting possible adaptive tail fiber gene shuffling. Despite this variability, these phages maintained broad but high specificity for Klebsiella species in this paper, including K. oxytoca, K. pneumoniae and K. aerogenes and several clinical Klebsiella isolates, with infectivity differences seen only in efficiency. This specificity for Klebsiella is consistent with the genus to which they belong (the Jiaodavirus, which contains only Klebsiella phages) and suggests they may be involved in the evolution of Klebsiella and be useful therapeutics.
    Keywords:  Jiaodavirus; Klebsiella phage; T4-like; clinical
    DOI:  https://doi.org/10.3390/v18040430
  15. Arch Razi Inst. 2025 Aug;80(4): 1005-1014
    Isolation and Characterization of Lytic Bacteriophages against Antibiotic-Resistant Klebsiella Pneumoniae from Wastewater Samples.
    Mokari Saba, Azizi Jalilian Farid, Shokri Somayeh, Teimoori Ali, Mahmoudvand Shahab.
      One of the most important global health problems in the last decade is the increasing prevalence of antibiotic-resistant Klebsiella pneumoniae. Phage therapy is considered a highly efficient alternative to treat antibiotic-resistant bacteria. Therefore, this study aimed isolate lytic phages against clinical strains of antibiotic-resistant Klebsiella pneumoniae from wastewater samples. In this study, different samples were collected, and the presence of phage was confirmed by a double layer test. The protein and genomic structure were verified using SDS- PAGE and RAPD- PCR techniques. Transmission electron microscopy (TEM) was used for the evaluation of morphology. The isolated phage's stability was assessed by subjecting it to different temperature and pH conditions. An adsorption assay test was conducted to determine the duration of phage absorption to corresponding host bacteria. In this study, we isolated three lytic phages (k.8, k.22, and k.34) that target K. pneumoniae. Transmission electron microscopy (TEM) results indicated that all three phages belong to the Siphoviridae family. Additionally, our investigation demonstrated that these phages remain stable within a temperature range of 4°C to 50°C and a pH range of 5.0 to 9.0. The adsorption assay tests showed that the isolated phages were able to attach to their corresponding host bacteria within 6 to 9 minutes. The present study demonstrated that the isolated phages targeting K. pneumoniae exhibited a favorable survival rate when subjected to pH and thermal treatments. Furthermore, the isolated phages exhibited a short latent period, indicating rapid adsorption to the host surface. These findings suggest the potential application of these phages in phage therapy. However, further studies in the field of phage therapy are required.
    Keywords:   Lytic Phage; Phage Therapy; Wastewater; Klebsiella Pneumoniae
    DOI:  https://doi.org/10.32592/ARI.2025.80.4.1005
  16. Cureus. 2026 Mar;18(3): e105964
    Multidrug-Resistant Serratia fonticola Causing Diabetic Foot Infection: A Rare Case Highlighting Emerging Antimicrobial Resistance.
    Ashish Jangid, Shalini Singh, Prashant Pandey, Dilip Chaurasiya, Shobhit Agarwal.
      Diabetic foot infections are commonly caused by Gram-positive cocci and Enterobacteriaceae. Isolation of Serratia fonticola is very rare. Here, we report a case of multidrug-resistant Serratia fonticola isolated from a chronic diabetic foot ulcer in a patient with poorly controlled diabetes. The case highlights the importance of microbiological evaluation in non-healing wounds and raises awareness of unusual resistant pathogens in routine clinical practice. A 56-year-old female patient with poorly controlled diabetes developed a non-healing foot ulcer following minor trauma. Culture revealed multidrug-resistant Serratia fonticola. The patient improved with glycemic control, debridement, and culture-directed antibiotics.
    Keywords:  ampc beta-lactamase; carbapenem resistance; diabetic foot infection; multidrug resistance; serratia fonticola
    DOI:  https://doi.org/10.7759/cureus.105964
  17. Ther Adv Respir Dis. 2026 Jan-Dec;20:20 17534666261444168
    Microbiome and its role in bronchiectasis.
    Yiting Pan, Jin-Fu Xu.
      Bronchiectasis (BE) is a chronic respiratory disease characterized by damage to the bronchial wall structure and permanent dilation of the bronchi. The symptoms include a persistent cough, excessive production of purulent sputum, and recurrent hemoptysis. Dysbiosis of the microbiome plays a crucial role in the progression of BE. An increased abundance of pathogenic bacteria, along with viral and fungal infections, is closely associated with disease severity and clinical outcomes. Next-generation sequencing technology has significantly enhanced the sensitivity and resolution of the airway microbiome, providing powerful tools for a more detailed characterization of the microecology of BE. However, certain challenges still exist in clinical applications of this technology. In addition, extra-airway microbiomes, such as the gut and oral microbiome, may participate in airway inflammation and immune regulation through the gut-lung axis and oral-lung axis. In this review, we summarize the characteristics of microbiome dysbiosis in BE and highlight the potential value of related biomarkers in disease classification, severity assessment, and prognosis. We also provide an overview of recent treatment advancements. A deeper understanding of the microbiome's role in BE may facilitate early diagnosis and the optimization of individualized treatment strategies.
    Keywords:  bronchiectasis; dysbiosis; gut-lung axis; inflammation; microbiome; next-generation sequencing; oral-lung axis; precision medicine
    DOI:  https://doi.org/10.1177/17534666261444168
  18. Antibiotics (Basel). 2026 Apr 13. pii: 396. [Epub ahead of print]15(4):
    Detection to Disruption: A Comprehensive Review of Bacterial Biofilms and Therapeutic Advances.
    Pranay Amruth Maroju, Angad S Sidhu, Amogh R Motaganahalli, Robert E Minto, Fatih Zor, Christine Kelley-Patteson, Rahim Rahimi, Aladdin H Hassanein, Mithun Sinha.
      Bacterial biofilms are structured microbial communities enclosed within a self-produced extracellular polymeric substance matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This matrix promotes adhesion, structural stability, and the development of heterogeneous microenvironments that restrict antimicrobial penetration and shield bacteria from host immune responses. As a result, biofilms are major contributors to chronic, recurrent, device-related, and difficult-to-treat infections, posing a major challenge for clinical management and antimicrobial stewardship. This review summarizes current understandings of biofilm biology, its clinical relevance, including the stages of biofilm development, the composition and protective roles of the matrix, and the physiological heterogeneity that arises during maturation. It also examines key mechanisms underlying biofilm tolerance and resistance, such as limited antibiotic diffusion, and sequestration, enzymatic inactivation, efflux pump upregulation, persister cell formation, and horizontal gene transfer. In addition, it highlights important clinical settings in which biofilms are implicated, including cystic fibrosis, chronic wounds, osteomyelitis, implant- or device-associated infections, and breast implant illness, in which persistent implant-associated biofilms and the resulting chronic inflammatory milieu have been hypothesized to contribute to local and systemic manifestations in a subset of patients. The review further discusses conventional and emerging approaches for biofilm detection alongwith real-time monitoring. Biofilm-associated infections remain difficult to eradicate because persistence is driven by multiple interconnected protective mechanisms. Effective management therefore requires integrated strategies that combine accurate detection with multifaceted therapies, including antibiotics alongside matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophages, metabolic reactivators, and nanotechnology-based delivery systems. Advances in multi-omics and system-level modeling will be essential for developing next-generation strategies to prevent, monitor, and treat biofilm-associated disease.
    Keywords:  antibiotic resistance; bacterial biofilms; biofilm detection; biofilm therapeutics; breast implant illness; chronic infections; device-associated infections; extracellular polymeric substance
    DOI:  https://doi.org/10.3390/antibiotics15040396
  19. Microbiol Spectr. 2026 Apr 30. e0400925
    Synergistic effects of halo-plaque forming phage cocktails against polymicrobial Acinetobacter baumannii and Staphylococcus aureus.
    Ampapan Naknaen, Arrita Rueangrit, Wanna Sudhikaran, Arnon Chukamnerd, Sanicha Chumtong, Sarunyou Chusri, Rattanaruji Pomwised, Komwit Surachat, Kamonnut Singkhamanan, Ruttayaporn Ngasaman.
      Antimicrobial resistance is a growing global health crisis, with polymicrobial infections caused by Acinetobacter baumannii and Staphylococcus aureus posing a significant healthcare challenge due to their synergistic virulence, multidrug resistance, high incidence, and association with severe outcomes. Accordingly, urgent alternative treatments are needed, with bacteriophage or phage therapy showing considerable promise. Here, we isolated six phage types based on plaque morphology, including small clear plaques (SCP; phiAR002 and phiAR004), medium clear plaques (MCP; phiAR010 and phiAR011), and hazy-halo plaques (HHP; phiAR014 and phiAR015). These phages demonstrate the ability to lyse a broad spectrum of several carbapenem-resistant A. baumannii strains collected from secondary and tertiary care hospitals in Thailand, highlighting their suitability for therapeutic applications. To broaden host range and enhance bactericidal activity, phage cocktails comprising the halo-forming phage (phiAR014) in combination with either SCP (phiAR002) or MCP (phiAR010), which are genetically and mechanistically distinct, were formulated and demonstrated synergistic effects, suppressing bacterial growth for up to 36 h. These relatively small myophages, SCP and MCP, possess larger genomes (around 165-188 kbp) compared with HHP (around 106 kbp), exhibit a longer latent period (30 min versus 20 min), and produce a greater number of progenies, yielding 678-882 PFU per infected cell compared with 255 PFU per infected cell for HHP. To demonstrate their therapeutic potential, the phage cocktails were further assessed in co-cultures of A. baumannii and S. aureus under both planktonic and biofilm conditions. Cocktails combining HHP with SCP or MCP exhibited significant synergistic antibacterial activity at MOIs of 10 and 100, with effects evident within 10 h and sustained for 24 h. Relative to individual phages and uninfected controls, the cocktails achieved greater bacterial reduction, decreasing A. baumannii by approximately 2 log₁₀ CFU/mL compared with single phages (and ~5 log₁₀ versus controls) and S. aureus by ~2 log₁₀ CFU/mL. Moreover, the cocktails significantly enhanced biofilm inhibition and eradication compared to single-phage treatments, demonstrating synergistic interactions. These findings indicate that halo phages represent promising therapeutic candidates with potent antibacterial and anti-biofilm activity against polymicrobial infections.IMPORTANCEPhages are promising therapeutic agents due to their host specificity and ability to penetrate biofilms via structural and enzymatic mechanisms. The halo-plaque phenotype, indicative of depolymerase activity, facilitates the degradation of extracellular polysaccharides and cell wall components, thereby enhancing infectivity and biofilm penetration. Based on phenotypic and genomic characterization, halo-forming phage cocktails were developed and demonstrated effective suppression of polymicrobial growth and disruption of established biofilms in A. baumannii and S. aureus co-culture models. These cocktails exhibited synergistic inhibition of planktonic growth, biofilm formation, and biofilm eradication. Phage replication and lysis of A. baumannii may promote the release of putative depolymerases and/or cell wall hydrolases that could potentially contribute to matrix degradation; however, further investigation is required to elucidate the precise mechanisms and enzymatic functions involved. Together, these findings would pave the way for advancing halo-forming phages and support the targeted engineering of tail fiber or spike proteins for therapeutic applications in multidrug-resistant polymicrobial infections.
    Keywords:  Acinetobacter baumannii; Staphylococcus aureus; co-infection; halo-phage; synergistic effects
    DOI:  https://doi.org/10.1128/spectrum.04009-25
  20. Virulence. 2026 Apr 29. 2664980
    Acinetobacter baumannii: Mechanisms of antibiotic resistance, quorum sensing regulation, and current therapeutic strategies.
    Jamil Allen G Fortaleza, Kevin Smith P Cabuhat, Christian Joseph N Ong, Ferdinand A Mortel, Grace D Bacalzo, Jose Jurel M Nuevo.
      Acinetobacter baumannii has emerged as a major global pathogen due to extensive resistance to last-resort antimicrobials, a high burden of nosocomial infections, and increasing community-acquired cases. Its adaptability is driven by diverse resistance mechanisms, including β-lactamase production, aminoglycoside-modifying enzymes, efflux pump overexpression, target-site mutations, and lipid A remodeling, all which limit treatment options and worsen clinical outcomes. Pathogenicity is further enhanced by quorum-sensing systems, particularly AbaI/AbaR, which regulate biofilm formation, virulence, and antimicrobial tolerance. Despite extensive research, resistance, quorum sensing, and therapeutic strategies are often examined separately, limiting mechanistic understanding. This review integrates current evidence on the interplay between resistance evolution, quorum sensing, and biofilm persistence, linking these to therapeutic vulnerabilities. It further evaluates emerging interventions, including optimized antibiotic combinations, immunomodulation, drug repurposing, bacteriophage therapy, and alternative approaches such as antimicrobial peptides, phytochemicals, nanotechnology, and photodynamic therapy to inform improved treatment strategies.
    Keywords:  A. baumannii; Biofilm-mediated persistence; horizontal gene transfer; multi-drug resistance; non-antibiotic
    DOI:  https://doi.org/10.1080/21505594.2026.2664980
  21. Int J Microbiol. 2026 ;2026 8509161
    From Sewage to Salvage: Complete Characterization of Arefeen1 Phage Against MDR Pseudomonas aeruginosa.
    Arefeen Haider, Tahsin Khan, Naimul Islam Faysal, Sezanur Rahman, Jannat Akther, Shovan Basak Moon, Nure Sharaf Nower Samia, Shakhinur Islam Mondal, Anowara Begum, Sudhangshu Kumar Biswas, Mustafizur Rahman, Mohammad Jubair.
      The escalating global threat of multidrug-resistant (MDR) Pseudomonas aeruginosa, designated by the WHO as a critical-priority pathogen, necessitates urgent development of alternative therapeutics. We present Pseudomonas phage Arefeen1, isolated from Bangladeshi wastewater, as a clinically translatable candidate with therapeutic potential. Comprehensive genomic characterization revealed a 46,021 bp strictly lytic genome (52.68% GC content) belonging to the Caudoviricetes class, completely lacking virulence factors or antibiotic resistance genes as confirmed by VFDB and ResFinder screening-a crucial safety profile for clinical application. Phenotypically, Arefeen1 demonstrated efficient in vitro lytic activity, exhibiting rapid replication kinetics (25-min latent period), high burst size (150 ± 12 PFU/cell), and robust production yields (≥ 109 PFU/mL post-PEG precipitation). Host range analysis showed 85.7% efficacy against a panel of clinically relevant MDR strains, including respiratory (PA_CU_1) and wound (MO_4642.012.002) isolates. Comparative genomics with 840 P. aeruginosa phages identified six unique genes encoding membrane-interaction proteins (CDS_0052/0058/0061) and a specialized tRNA complement, suggesting evolutionary adaptations for enhanced host range and translational efficiency. Its isolation from Bangladesh's unique microbial ecosystem provides a geographically optimized resource for LMICs disproportionately affected by antimicrobial resistance. These findings, combined with its clinical strain coverage, position Arefeen1 as a potential candidate for preclinical development and phage therapy implementation against this formidable pathogen.
    Keywords:  MDR Pseudomonas aeruginosa; lytic bacteriophage; phage therapy; therapeutic phage characterization; wastewater bioprospecting
    DOI:  https://doi.org/10.1155/ijm/8509161
  22. Front Microbiol. 2026 ;17 1744469
    Broad-spectrum phage cocktail targeting Campylobacter improves survival in Galleria mellonella, a bridging host model for poultry biocontrol.
    Estibaliz Ruiz-Santamaría, Amaia Lasagabaster, Gaizka Carregal, Katherine Miranda-Cadena, Estibaliz Mateo.
      Campylobacter jejuni and Campylobacter coli are the main agents of campylobacteriosis, a globally prevalent foodborne illness predominantly linked to the consumption of contaminated poultry products. The increasing antimicrobial resistance in Campylobacter requires innovative control strategies throughout the poultry production chain. Bacteriophages, highly specific bacterial viruses, represent a promising biocontrol approach capable of selectively targeting Campylobacter without disrupting the natural microbiota. However, early-stage validation in intermediate models, such as Galleria mellonella, is essential to ensure safety and efficacy before application in poultry, as has been established for other zoonotic pathogens. This study evaluated the in vitro and in vivo efficacy of a novel four-phage cocktail targeting Campylobacter. In vitro assays showed that the phage cocktail successfully lysed all 13 strains tested, and each individual phage displayed a broad lytic spectrum, with most strains being susceptible to multiple phages. In vivo virulence screening in G. mellonella revealed marked strain-dependent virulence, with only five of 13 strains reducing larval survival below 50%. Phage efficacy in vivo was optimized using C. jejuni CJE065, the most virulent strain in the model. The phage cocktail applied at MOI 10 increased the G. mellonella survival from 25.5% in untreated controls to 57.5% (p < 0.001), whereas lower MOIs provided only transient protection. Phage-antibiotic therapy combining phage cocktail and either erythromycin or ciprofloxacin further enhanced larval survival rates, reaching up to 88.8 and 83.8%, respectively (p < 0.001). Overall, these findings support the potential use of this phage cocktail as an early-stage intervention against Campylobacter and highlight G. mellonella as a suitable intermediate model for optimizing phage-based treatments while reducing the need for vertebrate models.
    Keywords:  Galleria mellonella; biocontrol; campylobacteriosis; infection model; phage-therapy; poultry
    DOI:  https://doi.org/10.3389/fmicb.2026.1744469
  23. Int Dent J. 2026 Apr 30. pii: S0020-6539(26)00192-9. [Epub ahead of print]76(4): 109598
    Reframing Periodontitis: A Concise Review of Shifting Paradigms and Contemporary Clinical Practice.
    Kodikara Mudiyanselage Chathurika Padmakumari, Pradeep Koppolu, Aruni Tilakaratne.
       INTRODUCTION AND AIMS: Periodontitis is a highly prevalent, chronic inflammatory disease that progressively destroys tooth-supporting structures, significantly impacting systemic health and patient quality of life. Given its global public health implications, a current, evidence-based understanding of periodontitis management is essential, particularly as therapeutic strategies have evolved rapidly. This paper critically traces the evolution of periodontitis management from historical paradigms to modern, evidence-based practices, highlighting how shifting conceptual frameworks have reshaped clinical decision-making and patient care.
    METHODS: A structured narrative literature review was conducted, analysing recent clinical studies, systematic reviews, updated classification systems, and internationally recognised treatment guidelines.
    RESULTS: This review highlights emerging paradigm shifts in the aetiopathogenesis, risk factors, and treatment of periodontitis. Advances in diagnostic tools and classification systems now enable refined, risk-informed, and personalised care pathways. Despite these improvements, the global prevalence of periodontitis remains high. Given that periodontitis is largely preventable, this work aims to re-engineer current therapeutic strategies to prioritise robust preventive measures. This approach is combined with updated, validated clinical protocols for curative treatment, aiming to drastically reduce the global burden of disease and its systemic impact.
    CONCLUSION WITH CLINICAL RELEVANCE: Current evidence-based guidelines underscore a shift toward personalised periodontal care, emphasising tailored, patient-specific management over 'one-size-fits-all' protocols. Future research must prioritise refining diagnostic precision and validating innovative, preventive strategies to bridge the gap between scientific advancements and everyday clinical practice.
    Keywords:  Adjuncts; Antibiotics; Biofilm; Clinical practice guidelines; Microbial; Periodontitis; Risk factors
    DOI:  https://doi.org/10.1016/j.identj.2026.109598
  24. J Oral Microbiol. 2026 ;18(1): 2662091
    Metagenome-based virome analysis identifies the oral viral signatures for periodontitis.
    Tianshu Chu, Jian Liu, Yue Zhang, Kai Yang, Shenghui Li, Qiulong Yan, Yuhong Li.
       Background: Periodontitis (PD) is a chronic infectious disease driven by bacterial biofilms, yet the oral virome's role in pathogenesis remains poorly understood.
    Objective: This cross-cohort meta-analysis aims to define PD-associated viral signatures, characterize predicted virus-host interactions, and evaluate the diagnostic potential of viral biomarkers.
    Methods: We integrated 89 saliva (44 PD, 45 healthy) and 86 subgingival plaque (48 PD, 38 healthy) metagenomes from six public cohorts for a unified virome analysis.
    Results: We identified 156 viral operational taxonomic units (vOTUs) significantly associated with PD (105 in saliva, 66 in subgingival plaque and 15 shared). PD-enriched vOTUs were predicted to target periodontal pathogens including Porphyromonas gingivalis, whereas Streptococcus-targeting phages were decreased. PD-associated vOTUs harbored diverse bacterial defense and anti-defense systems, with those enriched in PD overrepresenting lysozyme and replication-associated genes. Diagnostic models based on key viral markers achieved robust performance, with AUCs of 0.95 (saliva) and 0.92 (subgingival plaque) for classifying PD.
    Conclusion: This study delineates a distinct oral virome profile in PD, highlights predicted virus-host interactions, and underscores the potential of viral biomarkers for PD diagnosis,providing a basis for future investigations into viral ecology and phage-based interventions.
    Keywords:  Periodontitis; bacteriophage; biomarker; function annotation; metagenomics; oral virome
    DOI:  https://doi.org/10.1080/20002297.2026.2662091
  25. Int J Dent. 2026 ;2026 6236248
    Synergistic Roles of Fimbriae and Gingipain Genotypes in Porphyromonas gingivalis and Their Association With Periodontitis Severity.
    Manohar Kugaji, Kishore Bhat, Uday Muddapur, Ram Surath Kumar, Suman Kumar Ray, Eswar Kandaswamy, Vinayak Joshi.
       Objective: Porphyromonas gingivalis is a major periodontal pathogen periodontitis, with virulence mediated by fimbriae and gingipains. Differences in virulence may influence disease severity. This study aimed to assess the association and co-occurrence of fimbriae and gingipain genotypes and their relationship with clinical severity in periodontitis.
    Materials and Methods: This secondary analysis included 120 subgingival plaque samples from patients with periodontitis. Fimbriae (fimA types I-V) and gingipain (kgp, rgpA) genotypes were identified using PCR and restriction enzyme digestion, and P. gingivalis load was quantified by real-time PCR. Associations between genotypes and clinical parameters (probing depth and clinical attachment loss) were evaluated using Spearman's correlation and chi-square tests. Binary logistic regression assessed the association between periodontal disease severity and the presence of a combined virulence genotype, reported as odds ratios (ORs).
    Results: The fimA types II and III and gingipain genotypes kgp-I and kgp-II were significantly associated with deeper PD and greater CAL (p  < 0.05). fimA type II was the most prevalent across all bacterial load percentiles, followed by type IV. kgp-I and rgpA type A were correlated with higher P. gingivalis counts. Significant positive correlations were observed between fimbriae and gingipain genotypes (p  < 0.05). Patients with CAL ≥5 mm had significantly higher odds of harboring the combined virulence genotype than those with CAL <5 mm (OR = 3.56; 95% CI: 1.43-8.47; p = 0.011).
    Conclusion: Specific fimbriae and gingipain genotypes co-occur and are linked to increased bacterial load suggesting synergistic roles in the pathogenicity of P. gingivalis. The findings support the hypothesis that these virulence factors act synergistically to influence disease severity.
    Clinical Relevance: The integration of microbial virulence profiling with host immune response characterization may improve risk stratification and enable the development of personalized periodontal care strategies. Furthermore, microbial genotypic profiling may support the identification of disease-specific targets, thereby facilitating the implementation of tailored therapeutic interventions for effective periodontitis management.
    Keywords:  clinical severity; fimbriae; gingipain genotypes; p. gingivalis; periodontitis; virulence
    DOI:  https://doi.org/10.1155/ijod/6236248
  26. mBio. 2026 Apr 30. e0366825
    The Guild Model of CF Airway Microbial Ecology.
    Sage J B Dunham, Gregory A Willkeen, Ben Darby, Jodi M Corley, Andrea Hahn, Isaac Klapper, Heather D Bean, Lindsay J Caverly, Christina S Thornton, Christian Martin, Robert A Quinn, Stefanie Widder, Barbara A Bailey, Brandie D Wagner, Neha Garg, Paul J Planet, Ryan C Hunter, John J LiPuma, Forest Rohwer, Katrine L Whiteson.
      Ecological guilds are groups of organisms that utilize the same class of resources and occupy similar niches, regardless of their taxonomic identities. Here we propose the Guild Model for Cystic Fibrosis Airway Microbial Ecology, which considers the ecological function and wider role of each microbe in the ecosystem. This model consists of four functional guilds: (i) "Brewers" metabolize host-derived substrates (e.g., mucins) and produce fermentation products; (ii) "Drunkards" exploit the metabolic niche built by Brewers, consuming fermentation products and secreting exopolysaccharides to build biofilms; (iii) "Putrifiers" produce toxic compounds causing inflammation and tissue necrosis; and (iv) "Nihilists" are specialist pathogens characterized by intracellular or lytic life cycles and cytotoxin production. By focusing on microbial function and the broader community context, this model offers a refined framework for interpreting cystic fibrosis airway ecology. Although developed for CF, the Guild Model is adaptable to other diseases influenced by microbial ecology.
    Keywords:  airway microbiome; cystic fibrosis; ecological guilds; ecological modeling; host–microbe interactions; microbial ecology; polymicrobial infections
    DOI:  https://doi.org/10.1128/mbio.03668-25
  27. Int Dent J. 2026 Apr 29. pii: S0020-6539(26)00153-X. [Epub ahead of print]76(4): 109559
    Dental Pulp Stem Cells for the Management of Plaque Biofilm-Associated Infections : A Review.
    Shahrzad Aliniay-Sharafshadehi, Mohsen Sheykhhasan, Khaled Sharifi, Ali Ansari-Mohseni, Mohammad Hasan Yousefi, Hamed Afkhami, Aida Mehdipour, Mohammad Aghaali.
      This structured narrative review synthesises current evidence (2000-2025) on the antimicrobial, immunomodulatory, and regenerative properties of dental pulp stem cells (DPSCs) in the context of plaque-induced gingivitis and oral biofilm infections. We systematically reviewed peer-reviewed literature from PubMed, Scopus, and Web of Science via keywords related to DPSCs, oral biofilms, antimicrobial peptides (eg, β-defensins, LL-37), and immunomodulation. Unlike conventional antimicrobial therapies that solely target pathogen eradication, DPSCs offer a dual-function strategy: (1) direct microbial control through the secretion of antimicrobial peptides that disrupt Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and (2) resolution of inflammation via macrophage M2 polarisation, suppression of IL-1β/TNF-α (Interleukin-1β and Tumor Necrosis Factor-α), and microbiome rebalancing. Additionally, DPSCs support periodontal tissue regeneration through trophic signalling and differentiation into periodontal lineage cells. Critically, no clinical trials to date have evaluated DPSCs for the management of gingivitis. This review highlights DPSCs as promising, antibiotic-sparing therapeutic candidate and outlines key knowledge gaps for future translational research.
    Keywords:  Antimicrobial peptides; Dental plaque; Dental pulp stem cells; Gingivitis; Oral biofilm; Regenerative dentistry
    DOI:  https://doi.org/10.1016/j.identj.2026.109559
  28. Int Wound J. 2026 May;23(5): e70900
    Candida Drug Resistance in Patients With Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.
    Mohammad Hossein Ekvan, Hojjat Sayyadi, Sarina Alidadpour, Masoume Karimi, Muhammad Ibrahim Getso, Ahmad Reza Ebrahimi, Mohammad Mirpanahi, Omid Raiesi.
      Diabetic foot ulcers (DFUs) are one of the most serious and common complications that, if not treated properly, can lead to potential damage and even amputation. The aim of this systematic review and meta-analysis was to assess the drug-resistant Candida species in DFU. PubMed, Web of Science, Scopus and Google Scholar databases were systematically searched for eligible articles up to 22 June 2024. All articles on Candida diabetic foot infections that reported data on drug resistance were included in the study. In addition to general information, data on the type and number of fungi and the percentage of resistance to each drug were collected for analysis. A total of 238 studies were screened and finally, 16 articles were selected and analysed. Candida albicans was the most frequently isolated species in DFUs, followed by Candida tropicalis and Candida parapsilosis. For antifungal agents, the highest resistance was reported to Nystatin (32.48%, p-value = 0.30), Itraconazole (19.46%, p-value = 0.001) and Fluconazole (16.4%, p-value = 0.001). Miconazole (1.18%, p-value = 0.54) and Caspofungin (4.69%, p-value = 0.01) had the lowest resistance rates. For all drugs, resistance was higher in C. albicans than in non-albicans. This study found that antifungal drug resistance in Candida species is high in patients with DFUs, especially to itraconazole and fluconazole. Caspofungin, micafungin and voriconazole were more effective. Antifungal treatment in these patients should prioritize agents with lower resistance rates to improve outcomes and reduce the risk of treatment failure. Protocol Registration: PROSPERO-CRD42024567133.
    Keywords:   Candida ; diabetic foot; drug resistant; meta‐analysis; systematic review
    DOI:  https://doi.org/10.1111/iwj.70900
  29. Int J Chron Obstruct Pulmon Dis. 2026 ;21 598017
    A Quarter-Century of Chronic Obstructive Pulmonary Disease in the Intensive Care Unit (2000-2025): A Bibliometric Roadmap of Thematic Evolution and Future Frontiers.
    Yanyan Chen, Wen Wang.
       Background: Research on Chronic Obstructive Pulmonary Disease (COPD) in the Intensive Care Unit (ICU) has expanded rapidly, yet a comprehensive, longitudinal bibliometric analysis mapping its is scientific evolution lacking.
    Methods: We conducted a bibliometric analysis of 2,512 publications from the Web of Science Core Collection (2000-2025). A preliminary literature search confirmed no prior bibliometric study has specifically and systematically mapped this entire domain. Using VOSviewer and CiteSpace, we analyzed publication trends, collaborations, co-citation networks, and keyword bursts.
    Results: Annual publications show a consistent upward trajectory, with accelerated growth post-2019. The United States, China, and France are leading contributors, with robust international collaboration. The intellectual structure has evolved from foundational mechanical ventilation research to integrated management and prognostic modeling. Current research frontiers emphasize non-invasive ventilation, acute exacerbation management, and outcomes in multi-organ failure.
    Conclusion: This study provides the first quarter-century roadmap of ICU-focused COPD research, demonstrating its maturation toward data-driven and personalized care. By delineating the thematic evolution and identifying emergent interdisciplinary frontiers, such as data science integration and post-ICU recovery, this analysis offers a strategic guide for prioritizing research and optimizing care for this vulnerable population.
    Keywords:  COPD; ICU; bibliometric analysis; chronic obstructive pulmonary disease; intensive care unit; knowledge mapping; research frontiers
    DOI:  https://doi.org/10.2147/COPD.S598017
  30. J Oral Microbiol. 2026 ;18(1): 2662093
    Recent perspectives on precision-targeting therapy against oral biofilm.
    Lixuan Wu, Yuwang Tu, Suli Xiao, Jianchai Zeng, Guanwen Sun, Yijun Li.
       Background: Oral biofilm-derived diseases pose a significant clinical challenge due to their persistent nature and increasing drug resistance, contributing to a substantial global economic burden. Conventional treatments-such as mechanical debridement, antiseptic agents, and laser therapy-though partially effective, often lack specificity, resulting in non-targeted microbial killing and disruption of the ecological balance.
    Objective: This review provides an updated overview of the application of precision antimicrobial therapies against oral biofilms, with a particular focus on pH-responsive materials and bacteriophage-based strategies.
    Design: A comprehensive literature search was conducted across PubMed and Google Scholar databases from January 2016 to January 2026. A total of 84 full-text articles were included for qualitative synthesis.
    Results: The collective findings demonstrate that multiple precision-targeting strategies-spanning from bacteriophage therapy to pH-responsive antimicrobial materials-exhibit distinct advantages in combating oral biofilms.
    Conclusion: The common core principle underpinning these approaches lies in their 'precision-targeting' capability: the ability to identify and interfere with specific targets or biological processes. This attribute not only significantly enhances therapeutic efficacy but also paves the way for developing personalized, microbiome-preserving strategies for the prevention and management of oral diseases.
    Keywords:  Precision-targeting; bacteriophage; dental caries; oral biofilm; pH-responsive materials; periodontitis
    DOI:  https://doi.org/10.1080/20002297.2026.2662093
  31. Infect Immun. 2026 Apr 30. e0065225
    Enterococcus faecium colonization and persistence in a model of diabetic wound infection.
    Navin Jeyabalan, Frederick Reinhart Tanoto, Haris Antypas, Cheryl Jia Yi Neo, Rachel Jing Wen Tan, Kevin Pethe, David L Becker, Claudia J Stocks, Kimberly A Kline.
      Chronic wound infections are a common comorbidity of diabetes mellitus and can progress to amputation if untreated, yet effective strategies to manage these infections are limited. Commensals such as Enterococcus faecium and Staphylococcus epidermidis can transition into opportunistic pathogens when host defenses are compromised, underscoring the complexity of chronic wound microbiology. E. faecium, particularly vancomycin-resistant strains, is an understudied, clinically important cause of chronic diabetic wound infections. Using a low-dose streptozocin-induced diabetic mouse model, we characterized E. faecium wound infection dynamics and identified differences in colonization and clearance compared to non-diabetic animals. At 8 h post-infection (hpi), control mice exhibited higher E. faecium wound colony-forming units (CFUs) than diabetic mice but cleared the infection more efficiently, resulting in similar CFU by 24 hpi. By contrast, diabetic mice showed impaired clearance, with elevated CFU persisting through 72 hpi. In mixed species infection with S. epidermidis, S. epidermidis CFU increased at 72 hpi, while E. faecium CFU remained comparable to single species infection. Despite strong initial cytokine and neutrophil responses, E. faecium persisted in all wounds. Sustained neutrophil recruitment at 72 hpi occurred only in diabetic mice, whereas macrophage accumulation increased from 24 to 72 hpi in all wounds, including sterile controls. Histological analysis showed epithelial hyper thickening in both groups, indicating that diabetes and E. faecium each contribute to impaired wound healing. This study establishes a diabetic mouse model of E. faecium wound infection and suggests that E. faecium modulates innate immune responses to persist in the wound bed.
    Keywords:  Enterococcus faecium; Staphylococcus epidermidis; Staphylococcus lentus; biofilm infection; diabetes; immune response; mouse model; polymicrobial infection
    DOI:  https://doi.org/10.1128/iai.00652-25
  32. J Cyst Fibros. 2026 Apr 27. pii: S1569-1993(26)00098-6. [Epub ahead of print]
    A disrupted microbial network and an ecological shift towards anaerobes in NTM-infected cystic fibrosis patients.
    CIMeNT Study Group
      Nontuberculous mycobacteria (NTM) are increasingly recognized as opportunistic pathogens in people with cystic fibrosis (pwCF), but the ecological factors shaping their presence remain poorly understood. This study characterized the airway microbiota associated with NTM-positive culture using 16S rRNA gene sequencing of sputum from 108 pwCF (36 NTM-positive and 72 NTM-negative), matched by age, sex at birth, and CFTR genotype. Analyses integrated diversity metrics, differential-abundance modeling, multivariate regression, and microbial network inference, while accounting for Pseudomonas aeruginosa colonization. NTM-positive individuals exhibited slightly higher α-diversity and enrichment in strictly anaerobic taxa such as Alloprevotella tannerae, Stomatobaculum spp., and Prevotella nanceiensis, alongside reduced network connectivity. P. aeruginosa remained the dominant ecological driver, strongly reducing community diversity and structure. Partial Least Squares regression revealed that CFTR modulators (lumacaftor/ivacaftor) use and lung function (FEV₁%) were associated with distinct, commensal-enriched communities. In contrast, NTM status was associated with a distinct axis, indicating an independent ecological niche. Overall, NTM-positive cultures were associated with an anaerobe-enriched but less structured microbiota, likely reflecting localized hypoxia and biofilm-associated microenvironments rather than a direct effect of disease severity or modulator therapy. These findings highlight the role of airway microecology in NTM presence and provide a framework for understanding host-microbe interactions in chronic CF airway infections.
    Keywords:  Anaerobiosis / microbiology; Cystic Fibrosis / microbiology; Metagenomics / methods; Microbiota; Mycobacterium Infections, Nontuberculous / microbiology; Pseudomonas aeruginosa / physiology
    DOI:  https://doi.org/10.1016/j.jcf.2026.04.005
  33. Galen Med J. 2024 ;13(S Pt 1): e3730
    A State of Art Review: Volatile Organic Compounds and Periodontitis.
    Mohammad Ghasemirad, Omid Tavakol, Soroush Etesami, Kiana Nikeghbal, Dorsa Nikeghbal, Fatemeh Abedi Diznab, Reza Mahmoudi Anzabi.
      Periodontitis is a notable public health issue impacting more than 1 billion individuals globally, and its connection with volatile organic compounds (VOCs) has attracted growing interest. This review seeks to explore the existing knowledge on the link between VOCs and periodontitis.
    MATERIALS AND METHODS: An extensive literature review was performed to pinpoint key VOCs associated with periodontitis.
    RESULTS: The review revealed that several VOCs, such as hydrogen sulfide, methanethiol, indole, limonene, formaldehyde, 1,4-dichlorobenzene, 2-Aminothiazoline-4-carboxylic acid, ethyl acetate, methyl mercaptan, dimethyl sulfide, acetone, pyridine, picolines, o-xylene, mandelic acid, and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, are linked to periodontitis, with some contributing to heightened oral infection, direct tissue harm, oral malodor, and inflammatory responses, while the causality of this phenomenon remains unclear as it is uncertain which event occurs first.
    CONCLUSION: This review enumerates the VOCs that may either contribute to or arise from periodontitis; hydrogen sulfide appears to be the most extensively studied VOC in the context of periodontitis. This review highlights the intricate relationship between VOCs and periodontitis and underscores the necessity for additional research to clarify the mechanisms underlying this association and to guide the creation of effective prevention and treatment strategies.
    Keywords:  Hydrogen Sulfide; Methanethiol; Periodontitis; Volatile Organic Compounds
    DOI:  https://doi.org/10.31661/gmj.v13iSP1.3730
  34. Nat Rev Microbiol. 2026 Apr 27.
    Shared signals shape phages' lifestyles.
    Agustina Taglialegna.
      
    DOI:  https://doi.org/10.1038/s41579-026-01310-1
  35. Drug Ther Bull. 2026 Apr 27. pii: dtb-2025-000042. [Epub ahead of print]
    Update to the management of recurrent urinary tract infections in women aged 16 years and older.
    Leigh Sanyaolu, Haroon Ahmed, Miriam Santer, Sian Jones, Gail Hayward.
      Recurrent urinary tract infections (rUTIs) are a burdensome condition affecting approximately 6% or 1.7 million women in the UK. UTIs are also a common reason for antibiotic use, with UK data demonstrating that they are the second most common reason for antibiotic prescribing after respiratory tract infections. UTIs also result in significant healthcare costs, with hospital admissions alone estimated to have cost the National Health Service in England over £600 million from 2023 to 2024. This review provides an up-to-date overview of the management of rUTIs, focusing on the updated 2024 National Institute for Health and Care Excellence guidance, which recommends a stepwise approach starting with behavioural measures, then progressing to non-antibiotic and finally antibiotic prevention. It also compares the guidance with international recommendations and outlines the current evidence on pathogenesis, diagnostic approaches and treatment options, including behavioural measures, non-antibiotic interventions (eg, vaginal oestrogen and methenamine hippurate) and antibiotic prophylaxis. Key challenges in primary care are discussed, such as diagnostic uncertainty, patient dissatisfaction and antimicrobial resistance (AMR). Emerging research in point-of-care testing, the urinary microbiome and novel therapies is also highlighted. This review aims to support safe prescribing, improve patient satisfaction and mitigate AMR by promoting antimicrobial and diagnostic stewardship in the management of rUTIs.
    Keywords:  Antimicrobial Stewardship; Bacterial Infections; Primary Health Care
    DOI:  https://doi.org/10.1136/dtb.2025.000042
  36. Front Endocrinol (Lausanne). 2026 ;17 1724201
    The relationship between urinary albumin-to-creatinine ratio and bacterial profiles/inflammatory markers in diabetic foot infections: a retrospective cross-sectional observational study.
    Hao Wang, Fan Zhang, Gui-Ling Sun, Hui-Min Xu, Shao-Na Niu, Yan Peng.
       Background: Diabetic foot disease (including diabetic foot infection, DFI) and diabetic nephropathy (DN) are common diabetic complications. Patients with proteinuric DN are more likely to develop DFI, but data linking proteinuria and DFI are limited. We reviewed Urinary Albumin-to-Creatinine Ratio (UACR), pathogenic bacteria and inflammatory indicators of DFI patients from a northern Chinese tertiary hospital (2020-2023).
    Methods: We analyzed clinical data from 325 DFI patients, grouping them by UACR: normoalbuminuria (UACR < 30 mg/g), microalbuminuria (30 ≤ UACR < 300 mg/g), and macroalbuminuria (UACR ≥ 300 mg/g).
    Results: This is a single-center, retrospective cross-sectional observational study conducted at a tertiary hospital in northern China. We analyzed the association between UACR and the characteristics of DFI, and adjusted for potential confounding variables in the regression analysis, including glycemic control status, Wagner classification and peripheral vascular disease. This study included 325 DFI patients (66.8% male; 33.2% female), with average diabetes duration 11.9 ± 7.62 years and DFI duration 2.29 ± 0.35 months. We identified 447 bacterial isolates from secretions (193 Gram-positive, 241 Gram-negative, 13 fungi); 67.69% had single-bacterial infections, 32.31% polymicrobial. Bacteria types differed by UACR: normoalbuminuria group had mostly Gram-positive (55.04%, 50.26% Staphylococcus aureus); microalbuminuria group had more polymicrobial infections (40.71%) and dominant Gram-negative (61.21%); macroalbuminuria group also had more Gram-negative (58.57%). Higher UACR correlated with worse inflammation and metabolism.
    Conclusion: DFI patients with different UACR levels have distinct pathogenic bacteria. Higher UACR relates to worse inflammation and metabolic issues, suggesting a link between DN and DFI. Stratifying by UACR shows local DFI pathogen distribution, guiding clinicians' initial antibiotic use.
    Keywords:  Wagner classification; bacterial profiles; diabetic foot infection; diabetic nephropathy; inflammation
    DOI:  https://doi.org/10.3389/fendo.2026.1724201
  37. Philos Trans R Soc Lond B Biol Sci. 2026 Apr 30. pii: 20240346. [Epub ahead of print]381(1949):
    Bacterial quantitation in clinical infection: a systematic review.
    Amelia Benjamin, Koukeo Phommasone, Nicholas J White, Elizabeth A Ashley.
      Pivotal clinical studies of new anti-infective drugs enrol patients with strictly defined clinical syndromes, with clinical and laboratory endpoints used to define treatment success. Assessing bacterial killing in the host by serial quantitation has potential as a more efficient pharmacometric approach to assess antibiotic efficacy. We conducted a systematic review of the use of bacterial quantitation in clinical infection. The main syndromes studied in the 222 included articles were bacteraemia, chronic respiratory disease, diarrhoea, pneumonia and sexually transmitted infections. Most reports (135 articles, 61%) quantified bacterial load in different specimen types using quantitative polymerase chain reaction (qPCR). For bacteraemias, bacterial DNA load measured in whole blood by qPCR at clinical presentation was typically 2-3 log10 copies ml-1, usually substantially higher than the estimates from quantitative culture. Higher bacterial loads were associated with increased mortality in 28 of 35 studies. Faster bacterial clearance was correlated with appropriate antibiotic therapy and improved outcome in the majority of studies. Most studies sampled too infrequently for accurate characterization of bacterial clearance rates. The rate of bacterial clearance from blood or other compartments is an informative pharmacodynamic endpoint in the assessment of antibacterial therapeutic effects, but standardized approaches to assessment are needed based on optimal study design. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.
    Keywords:  DNA load; bacteria; colony count; quantitation; therapeutic response
    DOI:  https://doi.org/10.1098/rstb.2024.0346
  38. Antibiotics (Basel). 2026 Apr 09. pii: 383. [Epub ahead of print]15(4):
    Burn Infections and Sepsis: Challenges and Future Prospects of Antibacterial Therapy.
    Ghazaleh Dadashizadeh, Margarita Elloso, Marc G Jeschke.
      Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, biofilm formation, and dynamic shifts in microbial ecology toward multidrug-resistant organisms. Concurrently, profound and evolving changes in host immunity and metabolism reshape both susceptibility to infection and response to therapy. This review integrates current evidence across pathophysiology, microbiology, diagnostics, and treatment, with a focus on challenges that limit effective infection control in burn patients. Particular attention is given to diagnostic uncertainty arising from overlap between sterile inflammation and true infection, the clinical implications of biofilm-associated tolerance, and the impact of burn-specific pharmacokinetic variability on antimicrobial efficacy. We further examine emerging diagnostic and therapeutic innovations, including host-response profiling, rapid molecular detection platforms, and next-generation anti-infective strategies targeting microbial virulence, biofilm structure, and host immune pathways. Despite substantial scientific advances, translation into clinical practice remains constrained by limited burn-specific trials, heterogeneous definitions, and systemic barriers to antimicrobial development. Collectively, these challenges underscore the need for integrated, precision-based approaches that combine early source control, individualized antimicrobial optimization, and advanced diagnostic frameworks. Future progress will depend on coordinated efforts to standardize definitions, generate high-quality multicenter data, and align innovation with clinical applicability across diverse healthcare settings.
    Keywords:  antibiotics; burn; infection; resistance; sepsis
    DOI:  https://doi.org/10.3390/antibiotics15040383
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