bims-fagtap 2026-01-04 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2026–01–04
twenty-two papers selected by
Luca Bolliger, lxBio

Optical Density-Based Methods in Phage Biology: Titering, Lysis Timing, Host Range, and Phage-Resistance Evolution.
Phage Therapy for Bone and Joint Infections: Towards Clinical Translation.
Successful Systemic Phage Therapy for Implant-Associated MRSA Spondylodiscitis.
Clinical and Translational Perspectives on Bacteriophage Therapy for Nontuberculous Mycobacterial Diseases.
Exploring Bacteriophages as Potential Tools for Combating Multi Drug-Resistant Klebsiella pneumoniae: Isolation, Characterization, Genomic Insights, and In Vitro Evaluation.
Study of the Activity of the Staphylococcus aureus Phage vB_SaS_GE1 Against MRSA Clinical Isolates and Its Impact on the Formation of Dual-Species Biofilms with P. aeruginosa.
From Isolation to Application: Designing a Multi-Target Phage Cocktail for Bivalve Safety.
Pathobionts in the microbiome: Drivers of disease and targets for treatment.
Probiotic living microneedles designed by interbacterial competition for accelerated infected wound healing.
Bee Products and Traditional Plant Therapies for Wound Care: a comprehensive review of scientific evidence and clinical applications.
A Novel, Broad-Spectrum, Virulent Bacteriophage Targeting Yersinia pestis Isolated from the Soil of Wild Rodent Nests in Yunnan Province, China.
Micro/Nanorobots in Wound Healing: Bridging the Gap from Concept to Clinical Translation.
Gtr9 mutation trades phage resistance for carbapenem sensitivity to potentiate phage-meropenem therapy against carbapenem-resistant Acinetobacter baumannii in vitro.
AI vs. MD: Benchmarking ChatGPT and Gemini for Complex Wound Management.
Outsmarting Nightmare: Drug Resistance in Acinetobacter baumannii.
Antibiotic Resistance in Dentistry: A Review.
Developing machine learning classifiers for carbapenem resistance prediction in Klebsiella pneumoniae using Google's teachable machine.
Case Report: Bacteriophage-antibiotic therapy for extensively drug-resistant Acinetobacter baumannii in critically ill patient with respiratory infection.
Biofilm Formation and Its Relationship with the Microbiome in Pediatric Otitis Media.
3D-Printed Auxetic Hydrogel Dressings Reinforced With MXene and Carbonized Polymer Dots for Cascaded Antibacterial and Pro-Regenerative Effects in Wound Healing.
Overcoming Antibiotic Resistance and Treating Bacterial Infections with Biological Nanoparticles.
The Paradox of Healthcare in the 'Superbugs' Era: Current Challenges and Future Directions.

Viruses. 2025 Nov 30. pii: 1573. [Epub ahead of print]17(12):

Optical Density-Based Methods in Phage Biology: Titering, Lysis Timing, Host Range, and Phage-Resistance Evolution.

Stephen T Abedon.

  More than a century ago, bacteriophages (phages) were discovered as entities that could both replicate and dramatically reduce bacterial culture turbidities. By the late 1940s, phage impact on broth turbidity was being studied using electronic detectors. This review examines such turbidimetric, also known as colorimetric or optical density means of studying phage biology. The focus is especially on relatively rapid and higher throughput phenotypic phage characterization versus methods that rely instead on phage plaques, spots, or genotype determinations. Topics covered include (i) the most probable number method along with Appelmans' approach, (ii) estimation of phage growth parameters including especially that of phage lysis timing, (iii) consideration of lysis inhibition as a complicating factor, (iv) phage titering based on degrees of optical density change, (v) detection of both lysis from without and resistance to lysis from without, (vi) phage host-range determination, and (vii) study of post-lysis culture grow back, that is, of bacterial evolution of phage resistance. Based on over 30 years of experience using and studying optical density approaches to the exploration of broth-culture phage biology, the author takes a critical look at both the benefits and limitations of this increasingly common approach to phage biological characterization.

Keywords:  MPN; bacteriophage therapy; latent period; lysis profile; phage organismal biology; phage therapy; resistance suppression

DOI:  https://doi.org/10.3390/v17121573
Antibiotics (Basel). 2025 Nov 21. pii: 1187. [Epub ahead of print]14(12):

Phage Therapy for Bone and Joint Infections: Towards Clinical Translation.

Concha Ortiz-Cartagena, Lucia Blasco, Inés Bleriot, Jaime Esteban, María Dolores Del Toro, José Luis Del Pozo, María Tomás.

  Osteoarticular infections (OAIs), including osteomyelitis, septic arthritis, prosthetic joint infections, and facture-related infections, remain a major challenge due to biofilm formation and the prevalence of multidrug-resistant (MDR) pathogens. Although OAIs are predominantly caused by Staphylococcus aureus and coagulase-negative staphylococci, the increasing incidence of MDR Gram-negative infections adds further complexity to their management. Standard approaches, combining surgery and prolonged antibiotic therapy, frequently result in recurrence and poor outcomes. Bacteriophage (phage) therapy has emerged as a promising adjunct or alternative approach, offering high host specificity, replication at the infection site, and activity against biofilm-embedded bacteria. This review highlights recent advances in phage therapy for OAIs, focusing on administration routes (intravenous, intra-articular, topical, and oral) and on novel pharmaceutical delivery systems such as hydrogels, bone cements, microparticles, nanoparticles, and implant coatings. Preclinical and early clinical studies have analyzed phage stability, controlled release, and the synergistic effects of combined phage/antibiotic therapy. However, challenges remain regarding standardization, immunogenicity, and regulatory approval. Nonetheless, phage therapy shows promise for clinical translation as an adjunct or alternative to conventional treatments for OAIs. Well-designed clinical trials are urgently needed to confirm the efficacy of phage therapy, optimize delivery strategies, and integrate the treatments in routine practice. Despite encouraging outcomes for a successful clinical implementation, regulation and standardization of GMP production are required.

Keywords:  administration routes; delivery systems; osteoarticular infections; phage therapy

DOI:  https://doi.org/10.3390/antibiotics14121187
Int J Infect Dis. 2025 Dec 30. pii: S1201-9712(25)00574-0. [Epub ahead of print] 108357

Successful Systemic Phage Therapy for Implant-Associated MRSA Spondylodiscitis.

Simona Arientová, Ondřej Beran, Tomáš Belšan, Michal Holub.

  Systemic bacteriophage therapy was successfully used in a 60-year-old woman with multiple spinal stabilizations and chronic methicillin-resistant Staphylococcus aureus vertebral osteomyelitis unresponsive to antimicrobial treatment. After regulatory approval, she received 35 intravenous doses of customized anti-staphylococcal phages. The treatment was well tolerated and led to sustained clinical and laboratory remission.

Keywords:  Bacteremia; Bacteriophages; Methicillin-resistant Staphylococcus aureus; Vertebral osteomyelitis

DOI:  https://doi.org/10.1016/j.ijid.2025.108357
J Microbiol Biotechnol. 2025 Dec 29. 35 e2509030

Clinical and Translational Perspectives on Bacteriophage Therapy for Nontuberculous Mycobacterial Diseases.

Anwesha Ash, Cheol Moon, Jichan Jang.

  Mycobacterium abscessus complex (MABC) infections are among the most intractable challenges in clinical mycobacteriology because of their extensive intrinsic and acquired antibiotic resistance. Recent studies on compassionate use and a systematic 20-patient cohort study demonstrated that bacteriophage therapy is safe and generally well-tolerated, and it has been proven capable of inducing clinically meaningful improvements. Nevertheless, patient outcomes remain heterogeneous, largely because of antibody-mediated neutralization during intravenous administration and morphotype-dependent susceptibility, with smooth variants exhibiting resistance to currently available phages. Notably, phage resistance has rarely been observed in treated isolates, suggesting that durable efficacy is achievable when guided by pretreatment susceptibility screening. Emerging strategies, including phage engineering, lytic enzyme application, and liposomal encapsulation, are being developed to overcome intracellular barriers and immune clearance, whereas phage-antibiotic combinations have displayed synergistic activity. POSTSTAMP, the first prospective clinical trial, is establishing a structured framework for standardized evaluation. Collectively, these findings suggest that current compassionate use cases and small-scale cohorts provide a foundation for integrating bacteriophage therapy as a complementary strategy alongside antibiotics in future MABC treatment regimens.

Keywords:  Bacteriophage therapy; Mycobacterium abscessus; antibiotic resistance; compassionate use; nontuberculous mycobacteria; phage–antibiotic synergy

DOI:  https://doi.org/10.4014/jmb.2509.09030
Microb Pathog. 2025 Dec 30. pii: S0882-4010(25)00999-4. [Epub ahead of print] 108274

Exploring Bacteriophages as Potential Tools for Combating Multi Drug-Resistant Klebsiella pneumoniae: Isolation, Characterization, Genomic Insights, and In Vitro Evaluation.

Rahma E Ali, Amal S M Abo-Senna, Rasha A S El-Safty, Aliaa Aboulela.

  Bacteriophages are promising alternatives to antibiotics for combating multidrug-resistant (MDR) pathogens such as Klebsiella pneumoniae, a major cause of hospital-acquired infections. In this study, two K. pneumoniae-specific phages, vB_Kpn_RAH1 and vB_Kpn_RAH2, were isolated from sewage using an MDR clinical isolate (KP26) as the host. Their morphological, physicochemical, and genomic characteristics were analyzed. Both phages exhibited Siphovirus-like morphology, and the genome sizes of RAH1 and RAH2 were 46,784 bp and 59,380 bp, respectively. The phages were stable at 25-37 °C and pH 7-9 but were sensitive to high temperatures (80-90 °C), extreme pH, and prolonged UV exposure. Killing-curve assays confirmed strong bactericidal activity, with MOI 0.1 producing the most sustained bacterial reduction (90-97%), while higher MOIs showed reduced long-term efficacy. The phage cocktail exhibited superior and prolonged inhibition of K. pneumoniae, outperforming RAH1 and RAH2 individually. One-step growth analysis revealed burst sizes of approximately 400 virions for RAH1 and 250 for RAH2. Host-range analysis indicated narrow specificity for both phages, whereas their cocktail displayed a broader lytic spectrum, lysing 9 of 15 clinical isolates. The absence of lysis in non-Klebsiella species emphasizes the high specificity of the phages, supporting a targeted therapeutic approach while minimizing unintended effects on the host microbiota. Genomic analysis confirmed that RAH1 and RAH2 are novel species lacking antimicrobial resistance and virulence genes. RAH2 is strictly lytic, whereas RAH1 is temperate. The strictly lytic nature and favorable genomic features of RAH2 support its potential as a candidate for therapeutic applications.

Keywords:  Bacteriophage; Klebsiella pneumoniae; Multi-drug resistance (MDR); Phage therapy

DOI:  https://doi.org/10.1016/j.micpath.2025.108274
Viruses. 2025 Dec 16. pii: 1623. [Epub ahead of print]17(12):

Study of the Activity of the Staphylococcus aureus Phage vB_SaS_GE1 Against MRSA Clinical Isolates and Its Impact on the Formation of Dual-Species Biofilms with P. aeruginosa.

Nino Grdzelishvili, Davit Lazviashvili, Aleksandra Kurowska, Krzysztof Jakub Pawlik, Łukasz Łaczmanski, Elene Kakabadze, Elene Zhuravliova, Nina Chanishvili, Nata Bakuradze.

  Bacteriophage therapy is regarded as a promising alternative for treating and preventing antibiotic-resistant bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent and difficult-to-treat pathogens. S. aureus also contributes to the formation of both single- and mixed-species biofilms. Treating biofilms remains a major challenge for antibiotic-based eradication of pathogens, as the biofilm matrix provides a protective barrier for bacteria. The selection of highly active phages targeting S. aureus is therefore crucial for medical applications, given the high prevalence and drug resistance of this pathogen. In this study, S. aureus phage vB_SaS_GE1 (GE1) was isolated and characterized as a potential therapeutic agent. The phage was isolated and propagated, and its host range was determined using standard methods. Whole-genome sequencing and annotation of the phage DNA were performed. A time-kill assay and evaluation of the anti-biofilm activity of the Staphylococcus phage, both alone and in combination with Pseudomonas phage GEC_PNG3 (PNG3) on mixed-species biofilms, were conducted. The results indicated that GE1 is a lytic phage that does not carry virulence-determining genes. The time-kill assay demonstrated sustained lytic activity of GE1 without the emergence of phage-resistant mutants in the tested MRSA strains. Although phage treatment increased biofilm matrix production compared to the control, the viable cell count within the biofilms was reduced. Overall, the characteristics assessed indicate that vB_SaS_GE1 is safe and exhibits strong antibacterial activity against MRSA strains.

Keywords:  MRSA; P. aeruginosa; anti-biofilm activity; bacteriophage

DOI:  https://doi.org/10.3390/v17121623
Microorganisms. 2025 Nov 27. pii: 2708. [Epub ahead of print]13(12):

From Isolation to Application: Designing a Multi-Target Phage Cocktail for Bivalve Safety.

Pedro Costa, Carla Pereira, Jesús L Romalde, Adelaide Almeida.

  Narrow host specificity and bacterial resistance often limit single-phage treatments. Phage cocktails address these challenges by expanding the host range, reducing resistance, and enhancing bacterial inactivation. This study aimed to develop an optimised phage cocktail targeting Escherichia coli, Salmonella enterica serovar Typhimurium, Salmonella enterica serovar Enteritidis, and Aeromonas hydrophila, key pathogens in bivalve consumption. Twelve phages were isolated, purified, and screened for bacterial inactivation using resazurin-based viability assays. Host range analysis showed that all phages infected at least one additional bacterial species, with four (phEc4, phSE1, phAh2, phAh4) targeting three of the four bacteria. Cocktail formulation aimed to maximise bacterial reduction while balancing host range expansion with factors such as the risks of resistance development and inter-phage competition. Among the tested combinations, the most effective cocktail consisted of E. coli phage phEc3, S. Typhimurium phage phST1, S. Enteritidis phage phSE1, and A. hydrophila phage phAh2. Future studies should evaluate the cocktail's efficacy in vitro and assess both safety and performance in vivo in bivalve depuration systems.

Keywords:  bacterial viability; cocktail formulation; phage cocktail; phage isolation; screening assays

DOI:  https://doi.org/10.3390/microorganisms13122708
Microb Pathog. 2025 Dec 27. pii: S0882-4010(25)00993-3. [Epub ahead of print]211 108268

Pathobionts in the microbiome: Drivers of disease and targets for treatment.

Selvaraj Bharathi, Yolin Angel P A Soundara Rajan, Santhiyagu Prakash, Grasian Immanuel, Ramasamy Ramasubburayan.

  Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.

Keywords:  Commensal; Dysbiosis; Inflammatory diseases; Pathobiont; Therapeutic strategies

DOI:  https://doi.org/10.1016/j.micpath.2025.108268
Acta Pharm Sin B. 2025 Dec;15(12): 6571-6586

Probiotic living microneedles designed by interbacterial competition for accelerated infected wound healing.

Honglei Wang, Zibei Wu, Chen Gao, Wenhao Wang, Minglong Chen, Lin Yuan, Jiating Wang, Cairong Xiao, Yang Zhou, Fan Tong, Hanmei Li, Huile Gao, Xiang Gao, Jintao Fu.

  Probiotic therapy offers a promising strategy for chronic infected wound management through pathogen suppression and immune modulation. However, its efficacy remains restricted by weak competitiveness in pathogen-rich niches and poor penetration across biofilm barriers. Inspired by bacterial competitive interactions, we developed a multifunctional microneedle (MN) platform to overcome these limitations. Lactobacillus reuteri (Lr) was coated with poly-l-lysine-modified metal-phenolic networks (MPNs) encapsulating doxorubicin (DOX), yielding DOX@MPN-PLL@Lr (DMP@Lr). The engineered probiotics were incorporated into dissolving MNs enriched with nutrient broth to ensure excellent microneedle performance and probiotic function. This design leverages MPN multifunctionality to reduce early-stage pathogenic burden via photothermal-assisted bacterial killing and near-infrared (NIR)-promoted antibiotic release, thereby enhancing probiotic competitiveness. Meanwhile, MNs physically disrupt biofilms for precise delivery into deep infection sites. In vitro, DMP@Lr achieved >99.9% (5.5 log) bactericidal efficiency, and its MNs exhibited a 1.4-fold higher biofilm clearance compared with blank MNs. In vivo, a single DMP@Lr MN patch promoted 93.9% wound closure, demonstrating potent antibacterial activity and accelerated healing. This study presents an innovative, translatable probiotic-based MN therapy for the effective treatment of chronically infected wounds.

Keywords:  Anti-inflammatory; Antibacterial; Biofilm disruption; Infected wound healing; Lactobacillus reuteri; Metal–phenolic networks; Microneedles; Probiotic

DOI:  https://doi.org/10.1016/j.apsb.2025.10.029
J Pharmacopuncture. 2025 Dec 31. 28(4): 255-268

Bee Products and Traditional Plant Therapies for Wound Care: a comprehensive review of scientific evidence and clinical applications.

Ahmed A Rawwash, Emad Ahmed Fathy Hussein, Omar Mohammad Atta.

   Objectives: Natural substances with healing properties, especially medicinal plants and bee-derived products, have been integral to traditional medicine systems for centuries, contributing significantly to wound care. Their value lies in both their pharmacological roots and well-documented biological activities, including infection control, inflammation reduction, antioxidative protection, and tissue regeneration. This review highlights the scientific evidence supporting the efficacy of bee products and plant-based therapies in wound care, assessing their chemical composition, biological properties, and mechanisms of action.
Methods: A wide range of medicinal plants and bee products are examined for their recognized therapeutic roles, with emphasis on their ability to prevent infection, modulate inflammation, counter oxidative stress, and promote healing. The review also considers complementary plant therapies that may enhance the effects of bee-derived substances.
Results: Evidence from experimental and clinical studies demonstrates that natural products such as honey and propolis can effectively treat chronic wounds, including diabetic foot ulcers, by supporting tissue repair and preventing complications.
Conclusion: This review affirms the therapeutic potential of bee products and medicinal plants and supports their integration into modern wound management protocols, which are increasingly being validated through scientific and clinical research.

Keywords:  bee pollen; bee venom; honey; medicinal plants; propolis; wound healing

DOI:  https://doi.org/10.3831/KPI.2025.28.4.255
Pathogens. 2025 Nov 24. pii: 1195. [Epub ahead of print]14(12):

A Novel, Broad-Spectrum, Virulent Bacteriophage Targeting Yersinia pestis Isolated from the Soil of Wild Rodent Nests in Yunnan Province, China.

Ying Long, Youhong Zhong, Pan Liu, Chunpeng Mao, Haipeng Zhang, Liyuan Shi, Shaogui Zi, Xinyu Qin, Zongti Shao, Rongji Cao, Hongbaiyu Liu, Qingwen Gao, Ling Yang, Yuming Chen, Yuanying Shen, Peng Wang.

  As promising biological tools, bacteriophages offer broad potential applications in disease diagnosis, treatment, and food safety. This study is the first to isolate a novel bacteriophage, designated vB_YpP_JC53 (abbreviated JC53), from the soil of wild rodent nests in plague-endemic areas of Yunnan Province. This bacteriophage is a T7-like phage that has the broadest host range among all T7-like phages discovered to date and remains stable under varying temperature and pH conditions. Comparative genomic analysis through NCBI revealed that the nucleotide sequence of phage JC53 shares 94.98% homology (95% coverage) with phage PSTCR2, a member of the Solymavirus genus, while exhibiting substantially lower similarity to known Yersinia phages. Further phylogenetic and collinearity analyses demonstrate that JC53 represents an evolutionarily distinct lineage, clearly diverging from Yersinia-infecting, T7-like, and Shigella phages, suggesting the emergence of a novel evolutionary branch. Its low ANI values relative to Yersinia phages and mosaic genome organization indicate a complex evolutionary origin, reflecting the extensive diversity of environmental phage populations. Collectively, these findings support the designation of JC53 as a novel Yersinia phage. Genome sequencing revealed that JC53 has a genome size of 39,415 bp, with a total of 52 predicted open reading frames. The broad bacteriophage spectrum of JC53 challenges the long-standing perception that T4-like bacteriophages primarily depend on a wide host range. These findings suggest that, within plague foci, JC53 may maintain ecological fitness by targeting other bacteria rather than strictly relying on Yersinia pestis. As a result, JC53 holds potential as an ecological control agent with the potential to suppress plague transmission by regulating the microbial community structure within foci.

Keywords:  Yersinia pestis; broad-spectrum activity; genomic characteristics; novel bacteriophage; strong lytic activity

DOI:  https://doi.org/10.3390/pathogens14121195
Int J Nanomedicine. 2025 ;20 15343-15362

Micro/Nanorobots in Wound Healing: Bridging the Gap from Concept to Clinical Translation.

Yukun Liu, Kang Wang, Fangli Gao, Zhikai Xu, Xuan Zhao, Xiangjun Bai, Zhanfei Li, Guoyun Wan, Jian Yang, Yuchang Wang.

  Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure sores, pose a significant clinical challenge due to ongoing inflammation, biofilm development, and impaired tissue regeneration. Standard wound care methods often fail to address these complex barriers, highlighting the need for innovative solutions. Nanorobotics has emerged as a groundbreaking platform, enabling programmable, multifunctional systems capable of active navigation, biofilm penetration, modulation of the microenvironment, and targeted therapeutic delivery. This review systematically covers the design principles and functional components of micro-/nanorobots, including propulsion techniques, sensing and actuation mechanisms, and biomimetic surface modifications. We also examine their therapeutic potential in wound healing, focusing on drug delivery optimization, biofilm disruption, reduction of oxidative stress, immune regulation, and tissue regeneration support. The integration of nanorobotics with intelligent wound care systems offers real-time monitoring and closed-loop interventions, initiating a new era of "smart wound management." Finally, we address translational challenges such as biosafety, large-scale manufacturing, and regulatory pathways, and provide perspectives on future advancements toward clinically practical, intelligent nanorobotic wound therapies.

Keywords:  chronic wounds; drug delivery; micro/nanorobots; nano; nanorobots; wound

DOI:  https://doi.org/10.2147/IJN.S557042
Antimicrob Agents Chemother. 2025 Dec 30. e0135525

Gtr9 mutation trades phage resistance for carbapenem sensitivity to potentiate phage-meropenem therapy against carbapenem-resistant Acinetobacter baumannii in vitro.

Jun Luo, Min Liu, Wen Ai, Xiaoling Zheng, Lu Han, Kuo Huang, Changlin Zhang, Jinhong Fan, Qianyuan Li, Chunhua Luo.

  The combined use of phages and antibiotics offers an alternative avenue against multidrug-resistant bacteria. We have previously described the synergistic antibacterial effect of the phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii (CRAB). The study uncovers the underlying molecular mechanism of phage resistance in CRAB mediated by a novel stop-gain mutation in the gene gtr9. Through phenotypic characterization of pleiotropy, including reduction of capsular polysaccharide production and biofilm formation caused by the mutation in gtr9, we revealed an evolutionary trade-off mechanism whereby phage-resistant CRAB exhibits reduced carbapenem resistance. The zebrafish infection model demonstrated that these phage-resistant mutants were attenuated in virulence in vivo. Throughout continuous passage experiments in vitro, gtr9 mutants displayed the stability of decreased growth rate, phage resistance, and virulence reduction. The combination therapy between phage pB23 and meropenem in different matrices exhibited consistent synergistic antibacterial activity in vitro, demonstrating its potential therapeutic in vivo. Collectively, our study reveals a trade-off mechanism underlying phage-antibiotic synergy, thereby providing a novel insight into bacterial resistance evolution and demonstrating the therapeutic potential of this approach against CRAB infections.

Keywords:  Gtr9; carbapenem resistance attenuation; carbapenem-resistant Acinetobacter baumannii; phage-antibiotic synergy; trade-off mechanism

DOI:  https://doi.org/10.1128/aac.01355-25
J Clin Med. 2025 Dec 13. pii: 8825. [Epub ahead of print]14(24):

AI vs. MD: Benchmarking ChatGPT and Gemini for Complex Wound Management.

Luca Corradini, Gianluca Marcaccini, Ishith Seth, Warren M Rozen, Camilla Biagiotti, Roberto Cuomo, Francesco Ruben Giardino.

  Background: The management of hard-to-heal wounds poses a major clinical challenge due to heterogeneous etiology and significant global healthcare costs (estimated at USD 148.64 billion in 2022). Large Language Models (LLMs), such as ChatGPT and Gemini, are emerging as potential decision-support tools. This study aimed to rigorously assess the accuracy and reliability of ChatGPT and Gemini in the visual description and initial therapeutic management of complex wounds based solely on clinical images. Methods: Twenty clinical images of complex wounds from diverse etiologies were independently analyzed by ChatGPT (version dated 15 October 2025) and Gemini (version dated 15 October 2025). The models were queried using two standardized, concise prompts. The AI responses were compared against a clinical gold standard established by the unanimous consensus of an expert panel of three plastic surgeons. Results: Statistical analysis showed no significant difference in overall performance between the two models and the expert consensus. Gemini achieved a slightly higher percentage of perfect agreement in management recommendations (75.0% vs. 60.0% for ChatGPT). Both LLMs demonstrated high proficiency in identifying the etiology of vascular lesions and recognizing critical "red flags," such as signs of ischemia requiring urgent vascular assessment. Noted divergences included Gemini's greater suspicion of potential neoplastic etiology and the models' shared error in suggesting Negative Pressure Wound Therapy (NPWT) in a case potentially contraindicated by severe infection. Conclusions: LLMs, particularly ChatGPT and Gemini, demonstrate significant potential as decision-support systems and educational tools in wound care, offering rapid diagnosis and standardized initial management, especially in non-specialist settings. Instances of divergence in systemic treatments or in atypical presentations highlight the limitations of relying on image-based reasoning alone. Ultimately, LLMs serve as powerful, scalable assets that, under professional supervision, can enhance diagnostic speed and improve care pathways.

Keywords:  ChatGPT; Gemini; artificial intelligence; chronic wounds; complex wounds; large language models; teleconsultation; wound management

DOI:  https://doi.org/10.3390/jcm14248825
Can J Infect Dis Med Microbiol. 2025 ;2025 9591804

Outsmarting Nightmare: Drug Resistance in Acinetobacter baumannii.

Annepu Praveen, Amjuri Sinduja, Mukesh Kumar Yadav, Divakar Sharma, Amit Singh.

  Acinetobacter baumannii is a critical nosocomial pathogen recognized by the WHO as a top-priority threat due to its extensive drug resistance, particularly in carbapenem-resistant Acinetobacter baumannii (CRAB) strains. According to recent CDC reports, CRAB is one of the most urgent causes of hospital-acquired infections, driving longer hospital stays, higher costs, and mortality. This pathogen employs multiple resistance mechanisms, including efflux pumps, porins like OmpA, making it highly difficult to treat. Resistance is further shaped by β-lactamases, integrons, and mobile genetic elements. The emergence of MDR, XDR, and PDR strains signals the looming postantibiotic era, where conventional therapies are increasingly ineffective. While several reviews have provided in-depth analyses of individual mechanisms and some comprehensive overviews, this work provides a broad overview of resistance strategies and genetic determinants, including tet(A/B), cmlA, and mdfA. Importantly, we also highlight emerging alternatives such as novel emergent phage therapy (NEPT), which proactively counters antiphage resistance and nanoparticles (CNPs), which resensitize resistant isolates and enhance antibiotic efficacy. By combining mechanistic insights with emerging interventions, this review provides a comprehensive perspective on CRAB resistance and highlights research priorities for mitigating its global threat.

Keywords:  Acinetobacter baumannii; AgNPs; CNPs; CRAB; MDR; NEPT; antiphage resistance; beta-lactamases; drug resistance; efflux pumps

DOI:  https://doi.org/10.1155/cjid/9591804
Antibiotics (Basel). 2025 Dec 12. pii: 1259. [Epub ahead of print]14(12):

Antibiotic Resistance in Dentistry: A Review.

Mohammed Zahedul Islam Nizami, Iris Xiaoxue Yin, John Yun Niu, Ollie Yiru Yu, Chun Hung Chu.

  Background: The widespread use of antibiotics in dentistry has become a significant driver of the global rise in antibiotic resistance, posing serious risks to both oral and overall health. Objectives: This study aims to review antibiotic use in dentistry, elucidates the mechanisms of resistance development, identifies contributing factors, and discusses strategies to mitigate this growing global health threat. Methods: This narrative review examines current patterns of antibiotic prescribing in dentistry and evaluates evidence showing that antibiotics, although essential for preventing and managing odontogenic infections, are often prescribed unnecessarily or inappropriately. Results: The analysis highlights the growing resistance of key oral pathogens such as Streptococcus spp., Enterococcus faecalis, and Porphyromonas gingivalis, which increasingly limits the effectiveness of conventional treatments. Factors contributing to this trend include inconsistent adherence to clinical guidelines, patient pressure, and insufficient awareness of antibiotics stewardship among dental professionals. To address these challenges, the review emphasizes the importance of evidence-based prescription, strengthened stewardship programs, and the development of alternative therapies, including host-modulating agents and bacteriophage applications. Ongoing education and professional development are equally vital to enhance clinical judgment and promote responsible prescribing habits. Conclusions: Overcoming antibiotic resistance in dentistry requires coordinated effort among clinicians, researchers, educators, and policymakers. Expanding surveillance, enforcing stewardship-driven policies, and supporting innovation in therapeutic research are key to reducing antibiotic misuse and preserving their effectiveness. Through collective commitment and informed practice, the dental profession can play a crucial role in protecting antibiotic efficacy and promoting sustainable, high-quality patient care.

Keywords:  antibiotics; dentistry; drug resistance; oral health; prevention; public health

DOI:  https://doi.org/10.3390/antibiotics14121259
J Microbiol Methods. 2025 Dec 31. pii: S0167-7012(25)00301-X. [Epub ahead of print] 107385

Developing machine learning classifiers for carbapenem resistance prediction in Klebsiella pneumoniae using Google's teachable machine.

João V O Cruz, Felipe G Sacoda, Vitor H Moreau, Luis G C Pacheco.

  We developed neural network models trained with images from Klebsiella pneumoniae genomes, encoded via Chaos Game Representation, to predict carbapenem resistance. Both real (n = 168) and synthetic AI-generated (n = 200) images were used. The best-performing model, among the 72 developed, achieved up to 87.5 % accuracy on generalization datasets.

Keywords:  Antimicrobial resistance; Klebsiella pneumoniae; Machine learning

DOI:  https://doi.org/10.1016/j.mimet.2025.107385
Front Med (Lausanne). 2025 ;12 1716306

Case Report: Bacteriophage-antibiotic therapy for extensively drug-resistant Acinetobacter baumannii in critically ill patient with respiratory infection.

Jie Lin, Guiqin Dai, Lei Zhang, Pengli Xu, Pengfei Zhao, Yang Zhou, Hongzhou Lu, Mingbin Zheng.

  Extensively drug-resistant Acinetobacter baumannii (XDR A. baumannii) poses a crucial challenge due to high mortality and limited therapies. Here, we report the successful application of phage-antibiotic synergy in a critically ill patient with two months of ineffective antibiotic treatment. The patient was diagnosed with severe pneumonia due to recurrent infection of XDR A. baumannii, causing severe pulmonary dysfunction. A nebulized phage inhalation combined with intravenous administration of polymyxin B, amikacin, and fosfomycin successfully brought about measurable clinical improvements in 8 days. The clearance of XDR A. baumannii in sputum cultures, coupled with decreased partial pressure of carbon dioxide, substantial absorption of bilateral pulmonary lesions, reduced density of residual infiltrates, and decreased pleural effusion in the patient, collectively confirmed therapeutic efficacy. Our case indicate that bacteriophage-antibiotic therapy is promising to prevent the emergence of resistant mutants and enhance antibacterial efficacy in patient with similar infections.

Keywords:  Acinetobacter baumannii; bacteriophage therapy; drug resistance; pulmonary disease; respiratory infection

DOI:  https://doi.org/10.3389/fmed.2025.1716306
Microorganisms. 2025 Dec 04. pii: 2760. [Epub ahead of print]13(12):

Biofilm Formation and Its Relationship with the Microbiome in Pediatric Otitis Media.

Ana Jotic, Ivana Cirkovic, Nevena Jovicic, Bojana Bukurov, Natalija Krca, Katarina Savic Vujovic.

  Otitis media is among the most common pediatric illnesses globally, constituting a leading cause of antimicrobial prescriptions, recurrent medical consultations, and preventable hearing loss in early childhood. Traditionally regarded as a sterile cavity intermittently invaded by pathogens, the middle ear is now recognized as a dynamic ecological niche influenced by anatomical immaturity of the Eustachian tube, host immune development, and the composition of resident microbial communities. Increasing evidence demonstrates that microbial dysbiosis and the establishment of biofilms are central to the persistence and recurrence of disease. This review synthesizes current knowledge of the pediatric middle ear microbiome, highlighting how commensal organisms contribute to mucosal resilience and colonization resistance, whereas pathogenic bacteria exploit ecological disruption to establish biofilm communities. Biofilm formation provides bacteria with enhanced survival through immune evasion, altered microenvironments, and antibiotic tolerance, thereby transforming acute otitis media into recurrent or chronic states. Furthermore, studies demonstrate how adenoids act as reservoirs of biofilm-forming organisms, seeding the middle ear and perpetuating infection. The emerging ecological perspective emphasizes the limitations of conventional antibiotic-centered management and directs attention toward innovative strategies, including microbiome-preserving interventions, probiotic or live biotherapeutic approaches, and antibiofilm agents. By defining pediatric otitis media as a disorder of disrupted host-microbe equilibrium, future research may pave the way for precision-based preventive and therapeutic strategies aimed at reducing the global burden of this pervasive disease.

Keywords:  antibiofilm therapy; biofilm formation; microbiota dysbiosis; middle ear microbiome; pediatric otitis media

DOI:  https://doi.org/10.3390/microorganisms13122760
Small. 2025 Dec 31. e08633

3D-Printed Auxetic Hydrogel Dressings Reinforced With MXene and Carbonized Polymer Dots for Cascaded Antibacterial and Pro-Regenerative Effects in Wound Healing.

Chen-Yu Lee, Ya-Ting Hsu, Qian-Ci Huang, Pulikkutty Subramaniyan, Akhil K Paulose, Chih-Ching Huang, Tzu-En Lin.

  In this study, we develop a 3D bioprinted auxetic hydrogel dressing (MX/CPDs@PBGC) that incorporates Ti3C2Tx MXene (MX) and carbonized polymer dots (CPDs) for the simultaneous treatment of chronic wounds infected with multidrug-resistant (MDR) bacteria. The PBGC matrix, composed of polyvinyl alcohol (P), boric acid (B), gelatin (G), and citrate (C), provides enhanced mechanical strength, self-healing capability, and auxetic behavior, ensuring durability and adaptability to complex, mobile wound sites. The responsive release of CPDs and MXene enables the controlled delivery of therapeutics, adapting to the dynamic environment of chronic wounds. CPDs derived from mannose and arginine offer potent antibacterial and (pro-)regenerative activity, while MXene contributes antioxidative and anti-inflammatory functions. In a diabetic mouse model with MRSA-infected wounds, the hydrogel significantly accelerated healing, reduced bacterial load, and outperformed commercial 3 M antibacterial dressings. Histological analysis revealed enhanced collagen deposition, angiogenesis, and epithelialization, as well as increased polarization of macrophages toward the M2 phenotype. Additionally, treatment with MX/CPDs@PBGC resulted in a marked reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines, confirming effective infection control and modulation of inflammation. These results highlight the potential of MX/CPDs@PBGC as a multifunctional dressing for treating MDR-infected wounds and support its further clinical investigation.

Keywords:  3D bioprinting; advanced wound dressings; carbonized nanomaterials; hybrid materials; titanium carbide MXene

DOI:  https://doi.org/10.1002/smll.202508633
Int J Mol Sci. 2025 Dec 05. pii: 11780. [Epub ahead of print]26(24):

Overcoming Antibiotic Resistance and Treating Bacterial Infections with Biological Nanoparticles.

Boris Ponomarev, Natalia Ponomareva, Artyom Kachanov, Konstantin Evmenov, Sergey Brezgin, Anastasiia Kostyusheva, Vladimir Chulanov, Peter Timashev, Dmitry Kostyushev, Alexander Lukashev.

  For over eight decades, antibiotics have been the cornerstone of treating bacterial infections. However, the rapid rise of antibiotic-resistant pathogens has created an urgent need for alternative therapeutic strategies. Advances in nanotechnology offer a promising solution through the development of bio-derived nanoparticles. This broad class includes extracellular vesicles such as exosomes and bacterial outer membrane vesicles (OMVs), as well as bioengineered cell membrane-coated nanoparticles (CMNPs) that combine synthetic cores with natural membranes from diverse source cells. These particles possess unique physicochemical and biological properties, such as intrinsic bioactivity, biocompatibility, and structural versatility, that can be harnessed for antimicrobial therapy. This review synthesizes recent progress in the design, characterization, and application of biological nanoparticles for combating bacterial infections. We place particular emphasis on their mechanisms of action, therapeutic potential, and key research directions that could accelerate their translation into clinical use.

Keywords:  antibiotic resistance; drug delivery; exosomes; extracellular vesicles; outer membrane vesicles

DOI:  https://doi.org/10.3390/ijms262411780
Pathogens. 2025 Nov 24. pii: 1199. [Epub ahead of print]14(12):

The Paradox of Healthcare in the 'Superbugs' Era: Current Challenges and Future Directions.

Elenoire Sole, Marilena Trinchera, Silvia De Gaetano, Angelina Midiri, Giovanni Piccolo, Giuseppe Mancuso, Giovanni Schepici, Carmelo Biondo.

  Antibiotic-resistant microbes represent a growing problem for modern medicine and public health. Projections indicate that deaths from such infections could reach 10 million per year by 2050. Healthcare associated infections (HAI) are among the most significant causes of mortality and morbidity in hospitals, impacting millions of patients globally. The emergence of HAI is associated with resistance to antimicrobials, rapidly worsening the patient's condition. Antimicrobial resistance determines unresponsiveness to treatment, which can ultimately lead to severe complications such as sepsis and shock. It is estimated that one in every ten patients are susceptible to infection during their stay in hospital, with the microorganism responsible for the infection frequently proving resistant to antibiotics. Among the latter, CRE (carbapenem-resistant Enterobacteriaceae), CRAB (carbapenem-resistant Acinetobacter baumannii), CRPA (carbapenem-resistant Pseudomonas aeruginosa), vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus (MRSA), commonly referred to as 'superbugs', are a major cause of HAIs. The aim of the present study is to provide a comprehensive overview of the global epidemiology of healthcare-associated infections, with particular emphasis on their incidence, distribution over time, and correlation with the socioeconomic status of different countries. Furthermore, the review aims to evaluate the effectiveness of current preventive strategies in reducing the incidence and mortality associated with HAIs.

Keywords:  AMR; MDR; hospital-acquired infections (HAI); superbugs

DOI:  https://doi.org/10.3390/pathogens14121199