International Journal of Antimicrobial Agents最新文献

{"title":"Long-acting lipoglycopeptides compared to standard-of-care for the treatment of complicated gram-positive infections: A systematic review and meta-analysis.","authors":"Dominick Salvatore, Jaci Moore, Taylor D Steuber","doi":"10.1016/j.ijantimicag.2025.107581","DOIUrl":"10.1016/j.ijantimicag.2025.107581","url":null,"abstract":"<p><strong>Objectives: </strong>Long-acting lipoglycopeptides (LA-LGPs) are being used more frequently for the treatment of complicated Gram-positive infections, including osteomyelitis, prosthetic joint infections, bloodstream infections, and endocarditis. This systematic review and meta-analysis compared the efficacy and safety of LA-LGP to the standard of care (SOC) antibiotics for the treatment of these infections.</p><p><strong>Methods: </strong>A systematic literature search was conducted using PubMed, Medline, Embase, Cochrane, and Clinicaltrials.gov through November 2024. Prospective and retrospective comparative studies evaluating patients being treated for complicated Gram-positive infections were included. Interventions included multi-dose LA-LGP, including dalbavancin and oritavancin, vs. SOC antibiotics. Risk of bias was assessed using Cochrane RoB 2 and ROBINS-I tools. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was clinical success.</p><p><strong>Results: </strong>Fourteen studies (n = 1582 patients) were included. Studies included a wide array of indications and dosing schemes. LA-LGP was associated with significantly higher clinical success rates compared to SOC (RR = 1.14, 95% CI = 1.05-1.23, P < 0.01). No significant differences were observed for infection recurrence, mortality, adverse events (AEs), or serious adverse events (SAEs). LA-LGP was associated with fewer hospital readmissions. A subgroup analysis of bone and joint infections showed no significant difference in clinical success between LA-LGP and SOC.</p><p><strong>Conclusions: </strong>LA-LGP for the treatment of complicated Gram-positive infections resulted in similar efficacy and safety to SOC antibiotics and may be a reasonable alternative for such infections. Results should be interpreted with caution given the risk of bias and heterogeneity (PROSPERO Registration ID: CRD42024532465).</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107581"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced immunogenicity of SARS-CoV-2 antigen with aluminum adjuvant and polysaccharide nucleic acid fraction of Bacillus Calmette Guerin.","authors":"Jia Ji, Miaojin Zhu, Linwei Zhu, Zhiyong Liu, Shengmei Yang, Taoming Tang, Zhigang Wu, Danrong Shi, Jiale Zhang, Xiaodi Zhang, Hangping Yao","doi":"10.1016/j.ijantimicag.2025.107578","DOIUrl":"10.1016/j.ijantimicag.2025.107578","url":null,"abstract":"<p><p>Vaccine immunization strategies are crucial for eliciting vaccine-induced immune responses, particularly in immune compromised populations and older adults. In clinical practice in China, the polysaccharide nucleic acid fraction of Bacillus Calmette-Guérin (BCG-PSN) is extensively used as an immune modulatory agent. Herein, we describe a new immunization strategy using the SARS-CoV-2 antigen (original strain) with aluminum adjuvant and BCG-PSN. We evaluated whether BCG-PSN enhances humoral and cellular immune responses to the SARS-CoV-2 vaccine in K18-hACE2 and BALB/c mice by assessing antibody and germinal center (GC) responses, as well as the quantity and functionality of memory T cells in the spleen. At day 28 after the first immunization, the SARS-CoV-2 antigen with Alum, when combined with BCG-PSN, significantly elevated the levels of IgGantibodies. It significantly enhanced the spleen's GC structure, amplified the SARS-CoV-2 antigen-specific T cell response, and conferred protection to mice against the Delta variant challenge. This study provides a reference to evaluate immunization strategies for vaccines with high immunological efficacy, and the SARS-CoV-2 antigen combined with Alum and BCG-PSN enhances immunogenicity by significantly boosting cellular immune responses after vaccine administration. The study focuses on the impact of BCG-PSN on the SARS-CoV-2 antigen, examining its role in generating neutralizing antibodies (NAbs) and eliciting T cell responses.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107578"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of tenofovir alafenamide fumarate-based therapy compared to tenofovir disoproxil fumarate- and abacavir-based therapy in children and young people living with HIV in Europe.","authors":"Elizabeth Chappell","doi":"10.1016/j.ijantimicag.2025.107634","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107634","url":null,"abstract":"<p><strong>Objective: </strong>Effectiveness and safety outcomes were compared between those on tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) or abacavir (ABC), among children and young people living with HIV (CYPLHIV) aged 6-<25 years.</p><p><strong>Results: </strong>577 CYPLHIV received TAF, 428 TDF and 426 ABC. 96%/83%/55% were ART-experienced, median age at drug start was 15·8/14·6/12·5 years, and median duration of follow-up was 1·6/2·3/3·0 years, respectively. Among all ART-experienced CYPLHIV at drug start there was no difference in the proportion virologically suppressed at 48 weeks. However, in those suppressed at drug start, the proportion suppressed at 48 weeks was higher on TDF than TAF (p=0·008). There was no difference in time to suppression (amongst unsuppressed at start) or to viral failure. Among those on TAF, there were four serious adverse events, of which 1 (renal colic) was considered related to TAF and led to discontinuation. The rate of treatment-emergent grade≥1 laboratory events was highest on TAF (adjusted incidence rate ratio vs. TAF: TDF 0·74(0·56-0·99, p=0·046); ABC 0·69(0·53-0·88), p=0·004). Rates of grade≥1 LDL and total cholesterol events on TAF were comparable on ABC, but higher than TDF, with no difference in bone/renal markers. There was no significant difference in grade≥3 events (p>0·500), although numbers were small. The risk of discontinuation (for reasons other than optimisation/simplification/unknown reason) was lowest for TAF.</p><p><strong>Conclusion: </strong>Virological outcomes were similar across drugs. Rates of any grade laboratory events were highest on TAF, driven by higher rates of lipid events. As TAF uptake increases, studies with long-term follow-up are required.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107634"},"PeriodicalIF":4.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic Insights to Support Pneumonia Treatment in a Patient Co-Infected with Two Carbapenem-Resistant Bacteria.","authors":"Brooke N Curry, Nidhi Singh, Alan E Gross, Jackson V Watkins, Egon A Ozer, Arunkumar Karunanidhi, Kayley Sherwood, Osayamen Obanor, Nahed Ismail, Alan R Hauser, Zackery P Bulman","doi":"10.1016/j.ijantimicag.2025.107633","DOIUrl":"10.1016/j.ijantimicag.2025.107633","url":null,"abstract":"<p><p>Identifying optimal antibiotic therapy for patients infected with extensively resistant bacteria is challenging, particularly when there are multiple organisms at the infection site. Personalized time-kill assays (TKAs) can be used to test the pharmacodynamic activity of clinically relevant antibiotic combinations to help select appropriate therapy for these difficult-to-treat infections. We report a case of ventilator-associated pneumonia due to Pseudomonas aeruginosa and Providencia stuartii that were each carbapenem resistant. Due to the complex resistance phenotypes, the isolates were analyzed via TKAs during the patient's hospitalization to evaluate the activity of relevant antibiotic combinations. Using the patient's isolates, the TKAs showed that a combination of ceftazidime/avibactam and a polymyxin was synergistic against the P. aeruginosa whereas ceftazidime/avibactam plus aztreonam was slightly more active than ceftazidime/avibactam alone against the P. stuartii. The results of the TKAs helped to validate the patient's treatment regimen of aztreonam, ceftazidime/avibactam, and colistin (inhaled), which successfully treated the infection. Whole genome sequencing later revealed that the P. stuartii harbored a bla_OXA-48 carbapenemase while the mechanism of carbapenem resistance in the P. aeruginosa was likely due to OprD loss combined with extended-spectrum β-lactamase expression. The putative mechanism of cefiderocol resistance in the P. stuartii isolate was identified as a premature stop codon in the cirA-like gene combined with the presence of β-lactamases. The patient's carbapenem-resistant coinfection was successfully treated with agents that were validated in real time using personalized TKAs. TKAs may be useful to optimize combination antibiotic therapy for patients infected with extensively resistant bacteria.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107633"},"PeriodicalIF":4.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning in Antimicrobial Therapy for Critically Ill Patients: Optimizing Early Empirical Regimens, Individualized Dosing, and De-Escalation Strategies.","authors":"Xinyun Huan, Linlin Hu, Hao Li, Feng Yu, Hua Shao","doi":"10.1016/j.ijantimicag.2025.107632","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107632","url":null,"abstract":"<p><p>The complexity of critically ill patients leads to high pharmacokinetic (PK) variability and an increased risk of drug resistance. For this special patient group, antimicrobial treatment regimens require individualized strategies, as traditional treatment models may have certain limitations in clinical practice. Machine learning (ML) has emerged as a novel tool for processing multidimensional clinical data. It could identify complex patterns to enhance diagnostic accuracy, treatment optimization, and drug behavior predictions across diverse populations. Based on the underlying power of ML, this review highlights its application in three critical domains: (1) predictive modeling of antimicrobial resistance (AMR) patterns to optimize the empirical antibiotic selection and mitigate resistance development; (2) data-driven forecasting of drug exposure to guide personalized dose adjustments; and (3) identify patients who potentially require antibiotic de-escalation therapy and optimize antimicrobial drug use while ensuring therapeutic efficacy. Furthermore, this paper suggests that ML algorithms could be combined with population pharmacokinetic (PopPK) models to construct an analytical framework with superior predictive performance and maintain interpretability. This method could provide a more accurate quantitative analysis of the dose-exposure-response relationship of antimicrobial drugs in critically ill patients. Despite these advances, challenges persist in data quality, clinical validation, and ethical regulation. Future research might prioritize prospective clinical trials to bridge the gap between theoretical models and bedside applications.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107632"},"PeriodicalIF":4.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00176-1","DOIUrl":"10.1016/S0924-8579(25)00176-1","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 5","pages":"Article 107621"},"PeriodicalIF":4.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology, Treatment and Outcomes of Bloodstream Infections Due to MBL-Producing Enterobacterales in France: A Retrospective Study.","authors":"Benoît Pilmis, Laurent Dortet","doi":"10.1016/j.ijantimicag.2025.107630","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107630","url":null,"abstract":"<p><strong>Objectives: </strong>Bloodstream infections (BSI) due to metallo-β-lactamase (MBL)-producing Enterobacterales are linked to high mortality, but data from France remain limited.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter study in 86 French hospitals including 156 adult patients with confirmed BSI due to MBL-producing Enterobacterales (January 2023-February 2025). The primary outcome was 30-day all-cause mortality. Secondary outcomes included in-hospital mortality and resistance profiles. Clinical features, treatment, and mortality risk factors were assessed.</p><p><strong>Results: </strong>Day-7, 30-day and in-hospital mortality rates were 11.5%, 23.1% and 26.3%, respectively. Common treatments were ceftazidime-avibactam plus aztreonam (n=91), cefiderocol (n=24), and other active antibiotics (n=21). Independent predictors of mortality were ICU admission (aOR 2.96, 95% CI [1.12-7.88]), delay in active therapy (aOR per day 1.19, 95% CI [1.02-1.40]), and lack of source control (aOR 4.0, 95% CI [1.14-14.3]). Among patients receiving active therapy, 30-day mortality did not differ by regimen. Cefiderocol resistance (27.9%) was mainly seen in NDM-producing E. coli strains harboring penicillin-binding protein 3 (PBP3) modifications and CMY-type β-lactamases.</p><p><strong>Conclusions: </strong>MBL-producing Enterobacterales BSIs are associated with high mortality. Early appropriate therapy and source control are critical. Resistance to last-line agents such as cefiderocol and aztreonam-avibactam calls for optimized empirical treatment guided by rapid diagnostics.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107630"},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pharmacometric model assessing the in vitro synergistic effect of a bacteriophage-polymyxin B combination in a clinical multidrug-resistant K. pneumoniae isolate.","authors":"Aneeq Farooq, Sue C Nang, Heidi H Yu, Hasini Wickremasinghe, Mei-Ling Han, Yu-Wei Lin, Sebastian G Wicha, Jian Li","doi":"10.1016/j.ijantimicag.2025.107628","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107628","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella pneumoniae represents one of the most critical pathogens globally and bacteriophage (phage) therapy offers a promising alternative for treatment. Phage therapy poses challenges due to its high specificity and fast resistance development in bacteria. One promising option to overcome these challenges is combining phages with conventional antibiotics.</p><p><strong>Objective: </strong>This study investigates phage kinetics and pharmacodynamic interactions between novel phage pK8 and polymyxin B against a clinical multidrug-resistant K. pneumoniae.</p><p><strong>Methods: </strong>Time-kill assays with time-dissolved sampling of phages and bacteria were coupled with pharmacometric modelling to describe phage-bacteria kinetics and killing dynamics. Additionally, different interaction models were investigated to assess the observed synergy between phage pK8 and polymyxin B.</p><p><strong>Results: </strong>Key findings reveal that while polymyxin B alone showed no effect and phage pK8 alone was not efficacious enough to prevent the regrowth of K. pneumoniae II-503, their combined application resulted in notable bactericidal effects up to complete eradication. This was particularly notable in scenarios with higher phage doses. The developed pharmacokinetic/pharmacodynamic model describes synergy as bacterial resensitization to polymyxin B when combined with phage pK8.</p><p><strong>Conclusions: </strong>The study shows that phage pK8 and polymyxin B combination effectively combats a clinical polymyxin-resistant K. pneumoniae strain. These promising results pave the way for further in vivo studies to validate and refine treatment strategies for tackling multidrug-resistant infections.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107628"},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phage therapy: An international survey of attitudes and experiences amongst clinicians.","authors":"Riley D Alvarez, Emma Cl Finlayson-Trick, Ruby Cy Lin, Greg J German","doi":"10.1016/j.ijantimicag.2025.107627","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107627","url":null,"abstract":"<p><p>Phage therapy is a promising tool to combat the global threat of antimicrobial resistance. Clinicians, as part of interdisciplinary teams, play an integral role in identifying patients for therapy, delivering phages, and monitoring treatment outcomes and safety. As such, in the context of rapidly evolving regulatory landscapes, clinician insight is crucial for advancement of phage therapy. In this study, we describe the first published international anonymized survey aimed at identifying attitudes and experiences of clinicians and healthcare professionals towards phage therapy. We distributed the survey to participants in the Global Clinical Phage Rounds, a network of >300 phage clinicians, health professionals, and scientists, from October 15, 2024 - January 30, 2025. Thirty respondents representing North America, Europe, Oceania, Africa, and Asia completed the survey (response rate 9.6%). The majority of respondents were very well-informed about phage therapy and 93% would consider enrolling their patients in phage therapy randomized controlled trials. Respondents identified Pseudomonas aeruginosa, Klebsiella species, and Staphylococcus aureus as priority organisms and bone/joint, respiratory, and urinary tract infections as priority syndromes. Respondents had concerns about clinical use evidence, regulatory barriers, and accessing phage. Twenty respondents reported experience with phage therapy, so answered additional questions. These respondents acquired phages from sources like phage banks, industry, and importation from other countries. Respondents delivered phage therapy primarily in single-use cases via parenteral/intravenous, topical, or inhalation routes. Experienced respondents endorsed combinations of monitoring before, during, and/or after phage therapy. These results serve as a guiding initiative to improve phage therapy integration in healthcare.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107627"},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biofilm Maturation in Carbapenem-resistant Pseudomonas aeruginosa Is Regulated by the sRNA PA213 and Its Corresponding Encoded Small Protein.","authors":"Yongli Song, Jie Li, Yating Zhang, Lingge Su, Shuang Qin, Chunyan Wu, Guibo Song","doi":"10.1016/j.ijantimicag.2025.107625","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107625","url":null,"abstract":"<p><strong>Objectives: </strong>Biofilm formation is a key factor contributing to the persistence and resistance of carbapenem-resistant Pseudomonas aeruginosa (CRPA). This study aims to elucidate the regulatory role of PA213, a previously uncharacterized and hypoxia-inducible small RNA, in promoting CRPA biofilm maturation.</p><p><strong>Methods: </strong>We collected 113 clinical isolates for species identification and antimicrobial profiling. Comparative transcriptomic analyses were conducted between carbapenem-susceptible and resistant strains to identify functional sRNA candidates. The expression and structure of PA213 were characterized using qRT-PCR, RACE, and secondary structure prediction. A Flag-tagged PA213 fusion protein was confirmed by Western blot. PA213's phenotypic effects were assessed through assays of biofilm formation, motility, pyocyanin production, and extracellular matrix regulation. Biofilm architecture was visualized by SEM, and viability was analyzed via CFU counts and PI staining. Protein partners were identified via GST-pulldown and LC-MS, and interaction with OprI was confirmed through immunofluorescence and biochemical validation. The impact of PA213 on quorum sensing (QS) gene expression was examined by RT-qPCR based on RNA-seq datasets.</p><p><strong>Results: </strong>PA213 is a novel, uncharacterized sRNA that is highly expressed in clinical CRPA isolates. This sRNA featured a typical stem-loop structure and a 279-nucleotide open reading frame (ORF), which encoded a low-molecular-weight polypeptide. PA213 was significantly upregulated in clinical CRPA under hypoxia and encoded a small peptide with high conservation. Functionally, PA213 acted as a multifunctional regulator, enhancing biofilm formation, inhibiting pyocyanin synthesis, promoting swimming motility, and reducing virulence and pathogenicity. It enhanced biofilm formation during microcolony (12-48 h) and maturation (48-72 h) phases, without increasing EPS production or relying on the las/rhl QS pathway. It ensured sufficient functional bacterial density and maintained the three-dimensional structure of the biofilm by modulating viable bacterial proliferation. Mechanistically, the protein encoded by PA213 directly interacted with OprI, mediating spatial stabilization of mature biofilms.</p><p><strong>Conclusion: </strong>PA213 functions as a bifunctional sRNA-peptide regulator that promotes CRPA biofilm maturation via non-coding and protein-mediated mechanisms, offering new insights into hypoxia-responsive biofilm regulation and antimicrobial resistance evolution.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107625"},"PeriodicalIF":4.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}