International Journal of Antimicrobial Agents最新文献

{"title":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(25)00127-X","DOIUrl":"10.1016/S0924-8579(25)00127-X","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107572"},"PeriodicalIF":4.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605185","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":"Clinical Application of Customized and Non-customized Bacteriophage Therapy in Patients with Refractory/Resistant Bacterial Infections: A Systematic Review and Meta-analysis.","authors":"Yang Liu, Shuhua Thong, Wilfried Moreira, Jia Hao Yeo, Yang Zhong, Zhi-Soon Chong, Tse Hua Nicholas Wong, Shimin Jasmine Chung, Andrea Lay Hoon Kwa","doi":"10.1016/j.ijantimicag.2025.107570","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107570","url":null,"abstract":"<p><strong>Background: </strong>Patients with refractory/resistant bacterial infection face high mortality rates. Bacteriophage therapy (PT) is a viable solution, but clinical evidence remains fragmented. This review synthesizes current evidence on PT efficacy, safety, and implementation, with additional analysis by customization strategies: non-customized, customized selection, and customized production.</p><p><strong>Method: </strong>We examined clinical studies on PTs for refractory/resistant bacterial infections and pooled efficacy and safety outcomes by customization strategy from randomized controlled trials, observational studies, cohorts, case series, and case reports using a random-effects model. Subset sensitivity analyses were conducted, and individual patient data were further analyzed. Risk of bias was assessed for each study.</p><p><strong>Result: </strong>As of May 14, 2025, 16226 articles were identified, and 130 studies (1115 patients) were included: 559 non-customized, 451 customized selection, and 105 customized production. Risks of bias were low to serious. Clinical improvement (I² 88%) and bacterial eradication (I² 94%) rates were 72% (95% confidence interval [CI], 61-81) and 51% (95%CI, 30-72), respectively. Customized production group had the highest success rates (79% and 87%), albeit at a cost. Time taken for customization often resulted in delays in PT. Higher titers and multiple administration routes were associated with better bacterial eradication. Efficacy improvement compared to control was statistically insignificant. Adverse events were mild-to-moderate. Phage neutralization appeared before, during, and after PT cessation. Impacts on pharmacokinetics remain uncertain. Immunological markers varied across studies.</p><p><strong>Conclusions: </strong>PT shows promising clinical outcomes, but significant gaps in clinical evidence persist, warranting well-designed trials. Laboratory-based phage monitoring shows promise but requires systematic investigation.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107570"},"PeriodicalIF":4.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600329","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":"Development of multiplex recombinase polymerase amplification for the rapid detection of five carbapenemase (bla_KPC, bla_NDM, bla_OXA-48-like, bla_IMP, and bla_VIM) and ten mcr (mcr-1 to mcr-10) genes in blood cultures.","authors":"Kittitouch Tullayaprayouch, Thanawat Phuadraksa, Sirirat Luk-In, Sudarat Pornsuwan, Phiraphat Changkhundi, Sineewanlaya Wichit, Sakda Yainoy","doi":"10.1016/j.ijantimicag.2025.107567","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107567","url":null,"abstract":"<p><p>The emergence of plasmid-encoded carbapenemase and mobile colistin resistance (mcr) genes poses a significant challenge in controlling the spread of multidrug-resistant Gram-negative bacteria. Addressing this issue requires the development of rapid, accurate, and cost-effective tools for gene detection. For the first time, this study reports three multiplex recombinase polymerase amplification (RPA) assays, each designed to detect five resistance genes: carbapenemase (bla_KPC, bla_NDM, bla_OXA-48-like, bla_IMP, and bla_VIM), mcr-1 to mcr-5, and mcr-6 to mcr-10. Using agarose gel electrophoresis, all 15 target genes were successfully amplified by the three assays, demonstrating the potential of these assays for integration with rapid reporting platforms. To increase their applicability, the assays were combined with SYBR® Green I for visual identification of all 15 target genes and with lateral flow immunoassays (LFIAs) for detection of two carbapenemase (bla_NDM and bla_OXA-48-like) and two mcr genes (mcr-1 and mcr-3) genes. Specificity testing showed that RPA-SYBR® Green I and RPA-LFIAs produced no cross-reactivity among the target genes. The limit of detection for RPA-SYBR®Green I, for all genes, ranged from 2 × 10⁰ to 2 × 10² CFU/reaction, and for RPA-LFIAs from 2 × 10⁰ to 2 × 10³ CFU/reaction. The developed RPA-SYBR® Green I and RPA-LFIAs successfully detected 15 and 4 target genes, from positive hemoculture bottles. These assays offer a promising approach for point-of-care testing. Providing a valuable tool for antimicrobial resistance surveillance and timely guidance for effective antibiotic intervention.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107567"},"PeriodicalIF":4.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575388","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":"Bacteriophage-enhanced doxycycline activity against Escherichia coli in chronic bacterial prostatitis.","authors":"Novella Cesta, Alessandro Fusco, Caterina Ferretti, Alessandro Materazzi, Anna Altieri, Cartesio D'Agostini, Marco Iannetta, Massimo Andreoni, Arianna Tavanti, Loredana Sarmati, Mariagrazia Di Luca","doi":"10.1016/j.ijantimicag.2025.107571","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107571","url":null,"abstract":"<p><strong>Objectives: </strong>Prostatitis caused by antibiotic-resistant Escherichia coli pose a significant treatment challenge. Phage therapy is emerging as a promising antibacterial strategy. We report the case of a patient with a prostatitis caused by an ESBL-producing E. coli successfully treated with with oral doxycycline and two phage cocktails. The use of doxycycline was supported by the detection of Mycoplasma spp. in the patient's urine. We also tested the same phage-antibiotic combination against a panel of different E. coli strains in vitro.</p><p><strong>Methods: </strong>A patient received oral SES and PYO phage cocktails alongside oral doxycycline for 30 days. The MIC values of doxycycline and phages alone and in combination were evaluated by checkboard assay versus five E. coli isolates, including the patient's strain. Synergy was assessed using a modified fractional inhibitory concentration (FIC) index. Data were analysed by synogram and interaction plot based on the percentage reduction of the absorbance values (OD570) between untreated control and treated samples. Growth curves were performed over 24 hours to monitor bacterial replication in presence/absence of phage and/or antibiotic.</p><p><strong>Results: </strong>After treatment, microbiological cultures were negative, and symptoms remitted. In vitro, synergy/additive effect between doxycycline and phages was observed in three out of five E. coli isolates. Synogram analysis showed the synergistic effect versus one strain, while an additive effect was observed for the other four isolates. Growth curve analysis demonstrated enhanced bacterial growth inhibition for up to 12 hours with the combined treatment compared to either therapy alone.</p><p><strong>Conclusions: </strong>Although the E. coli strain was resistant to doxycycline, the antibiotic was administered specifically to target the Mycoplasma infection. Interestingly, the enhanced in vitro activity observed when the antibiotic was combined with phages versus E. coli suggests that this combination may be effective in eradicating chronic prostatitis caused by ESBL-producing E. coli.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107571"},"PeriodicalIF":4.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567419","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":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2025.107558","DOIUrl":"10.1016/j.ijantimicag.2025.107558","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"66 3","pages":"Article 107558"},"PeriodicalIF":4.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548778","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":"Multi-omics reveals the synergistic mechanism of polymyxin B and diethyldithiocarbamate against Pseudomonas aeruginosa.","authors":"Yanan Bai, Pengqin Chen, Wenhao Wu, Qing Yang, Tingting Qu, Wuping Shuai, Yongzhong Du, Saiping Jiang","doi":"10.1016/j.ijantimicag.2025.107569","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107569","url":null,"abstract":"<p><p>Resistance to polymyxin B (PMB) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become a global issue. A promising approach to rescue PMB treatment failures is to repurpose non-antibiotics as adjuvants to enhance the efficacy of antibiotics against CRPA. Here, we identified that the combination of PMB and diethyldithiocarbamate (DDC) had a high synergistic effect against PMB-resistant Pseudomonas aeruginosa (P. aeruginosa) strains in vitro and significantly hindered the biofilm formation. The PMB/DDC combination was effective in treating PMB-resistant P. aeruginosa infection model in vivo, as evidenced by higher survival rates in five days and lower bacterial loads in lung tissue and liver. Comprehensive multi-omics analysis revealed that the resistance of P. aeruginosa P2550 to PMB was determined by chromosomally encoded rather than plasmid-mediated mobilized colistin resistance (MCR) clusters. The combination down-regulated the expression of the operons arnBCADTEF at 2 h, which regulate LPS modification, and the abundance of metabolites of amino sugars and nucleotide sugars related to Lipid A biosynthesis and Lipid A modification were significantly perturbed. The Gac/Rsm pathway, quorum sensing (QS) system, cAMP/Vfr signaling, and c-di-GMP signaling, which are pathways associated with biofilm formation, were significantly inhibited within the first 4 h. In addition, the PMB/DDC combination significantly disturbed metabolic pathways, including arginine biosynthesis, the tricarboxylic acid cycle (TCA), and nucleotide metabolism. Notably, PMB alone, DDC alone, and the combination disrupted membrane-associated glycerophospholipid metabolism. The study highlights the potential of the PMB/DDC combination for treating PMB-resistant P. aeruginosa infections and elucidates the synergistic bactericidal mechanism of the combination through multi-omics methods.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107569"},"PeriodicalIF":4.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567421","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":"Long-distance transmission of tmexCD1-toprJ1 positive Klebsiella pneumoniae between humans and food animals.","authors":"Chao Liu, Pengcheng Du, Ping Yang, Yunfei Tang, Juan Yi, Qiaojun Wang, Chunjing Du, Ming Lu, Ruichao Li, Ning Shen","doi":"10.1016/j.ijantimicag.2025.107566","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107566","url":null,"abstract":"<p><strong>Objectives: </strong>The tmexCD1-toprJ1 RND efflux pump gene cluster is predominantly identified among Klebsiella pneumoniae (Kp) from humans and food animals. However, the mechanism of the long and rapid dissemination of such resistance determinant among strains from humans, food animals and the environment is unclear.</p><p><strong>Methods: </strong>Kp isolates were collected from two surveillance projects among patients and food animals. Whole-genome sequencing for phylogenetically close-related tmexCD1-toprJ1-positive and negative isolates, and phylogenic, plasmid stability and fitness cost analyses were performed.</p><p><strong>Results: </strong>Among 2592 clinical Kp isolates and 243 Kp isolates from food animals, the minimum inhibitory concentrations of tigecycline were 2 to 32 mg/L. The tmexCD1-toprJ1-positive isolates belonged to five sequence types (STs) and exhibited tigecycline resistance. By phylogenetic analyses, we have shown that tmexCD1-toprJ1-positive ST22 may have derived from tmexCD1-toprJ1-negative isolates in our hospital, whereas tmexCD1-toprJ1-positive ST726 showed a long-distance transmission among human and food animals. Different types of plasmids harboring tmexCD1-toprJ1 were identified, which have been disseminated among bacteria from humans, food animals and the environment. Interestingly, low fitness costs of the tmexCD1-torpJ1-positive isolates compared to the phylogenetically close tmexCD1-toprJ1-negative isolates.</p><p><strong>Conclusions: </strong>The long and rapid transmission of tmexCD1-toprJ1 was predominantly caused by plasmids. In One Health, systematic surveillance and studies of isolates from different sources, are urgently needed to understand the mechanism of resistance genes dissemination.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107566"},"PeriodicalIF":4.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567420","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":"Large scale laboratory evolution uncovers clinically relevant collateral antibiotic sensitivity.","authors":"Farhan R Chowdhury, Veronica Banari, Vlada Lesnic, George G Zhanel, Brandon L Findlay","doi":"10.1016/j.ijantimicag.2025.107564","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107564","url":null,"abstract":"<p><p>The increasing prevalence of antibiotic resistance is a critical challenge, necessitating the development of strategies to mitigate the evolution of resistance. Collateral sensitivity (CS)-based sequential therapies have been proposed to mitigate resistance evolution. However, the evolutionary repeatability of CS across different experimental conditions and its clinical relevance remain underexplored, hindering its potential for translation into clinical practice. Here, we evolve 20-24 lineages of E. coli against tigecycline (TIG) and piperacillin (PIP), antibiotics suggested to produce CS, through three separate laboratory adaptive evolution (ALE) platforms to test for the robustness of CS interactions and the effect of the choice of ALE on CS evolution. We generate over 130 resistant mutants and 540 resistance and collateral sensitivity measurements to identify a CS relationship between TIG and polymyxin B (POL) that is highly repeatable across all the ALEs tested, suggesting that this CS interaction is preserved across different evolution microenvironments. We determine the mechanism of this novel CS by showing that cells resistant to TIG deactivate the Lon protease and overproduce negatively charged exopolysaccharides, which in turn attracts the polycationic POL and renders cells hypersensitive to the drug. We find that this CS relationship is present in a clinical dataset of over 750 uropathogenic MDR E. coli isolates, and show that the soft agar gradient evolution (SAGE) platform best predicts collateral effects (CS, neutrality or cross resistance) in this dataset. Our study provides a framework for identifying robust CS with clinical implications that can reduce the emergence of resistance to our existing antibiotics.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107564"},"PeriodicalIF":4.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564777","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":"Human serum lipids affect Staphylococcus aureus sensitivity to phage infection.","authors":"Claudia Campobasso, Elisa Fausti, Daria Bottai, Barbara Turchi, Novella Cesta, Laura Rindi, Giulia Freer, Arianna Tavanti, Mariagrazia Di Luca","doi":"10.1016/j.ijantimicag.2025.107568","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107568","url":null,"abstract":"<p><p>To explore phage therapy as an alternative for targeting multidrug-resistant bacterial strains, it is crucial to study phage-bacteria interaction under conditions that mimic in vivo environments. Recent studies have demonstrated that staphylococcal phage activity can be significantly hindered by human blood components, including plasma and serum. This study aimed to identify serum components responsible for phage inhibition and assess whether this effect occurred across multiple Staphylococcus aureus strains. Phage Sb-1 activity against S. aureus ATCC 43300 was tested by pre-incubating or co-incubating bacteria and phages with 30% (v/v) heat-inactivated (56°C and 80°C) human, bovine, or foetal calf serum, IgG-depleted or delipidated serum, and BSA. Bacteria were incubated with serum before phage exposure, followed by washing with 0.1% Triton X-100. Additionally, growth kinetics of ten S. aureus strains incubated with or without Sb-1 were assessed over 24 hours in the presence of human serum. We found that adult human serum completely impairs phage infectivity due to interactions between serum components and bacterial cells rather than direct phage neutralisation. Albumin, IgG, and thermolabile components were demonstrated not to significantly contribute to the inhibitory effect, whereas lipids were identified as playing a key role. Furthermore, the sensitivity of different bacterial strains to phages was shown to be differentially affected by the presence of serum, as two of the strains tested remained susceptible to lysis despite serum exposure. Taken together, our findings suggest that serum lipid fraction impacts phage infectivity in a strain-specific manner, highlighting the need for tailored approaches for phage therapy.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107568"},"PeriodicalIF":4.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564766","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":"Lyophilised fecal microbiota transfer in capsules for recurrent Clostridioides difficile infection.","authors":"Lourdes Daneri, Alicia Urbano, Rosa Escudero-Sánchez, Ana Verónica Halperin, Ana Moreno-Blanco, María Dolores Corbacho, Cecilia Suárez-Carantoña, Concepción Rodríguez-Jiménez, Sergio Serrano-Villar, Rosa Del Campo, Javier Cobo","doi":"10.1016/j.ijantimicag.2025.107561","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2025.107561","url":null,"abstract":"<p><strong>Background: </strong>Recent guidelines recommend fecal microbiota transplantation (FMT) for patients who experience multiple episodes of Clostridioides difficile infection (CDI). The availability of lyophilised and encapsulated FMT in recent years has greatly improved patient comfort and convenience. While the effectiveness of FMT in oral capsules seems comparable to that achieved through other routes, further experience is needed, particularly in Europe, where there is currently limited published experience. The objective of this study was to present our experience with this therapeutic modality.</p><p><strong>Methods: </strong>A retrospective cohort study on patients with recurrent CDI treated by lyophilised, encapsulated FMT. All patients were followed for a minimum of 12 weeks. The primary outcome was recurrence at three months.</p><p><strong>Results: </strong>A total of 36 patients received 38 FMTs. The median age of the cohort was 78.5 years, with a median of four previous episodes. At the three-month follow-up, 27 of the 36 patients (75.0%) were free of CDI. One patient exhibited recurrence before the six-month mark. Two of the ten patients with FMT failure were successfully rescued with a second FMT. Of the nine patients who underwent rescue attempts, seven did not experience recurrence, resulting in a cure rate of 91.7% for the 36 patients. We did not detect severe adverse effects related to the FMT.</p><p><strong>Conclusion: </strong>We confirm an acceptable effectiveness of lyophilised capsulated oral FMT. Interestingly, most patients with FMT failure can be cured with a new treatment, which need not necessarily be a new FMT.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":" ","pages":"107561"},"PeriodicalIF":4.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560079","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}