Antimicrobial Agents and Chemotherapy最新文献

{"title":"A screen to identify antifungal antagonists reveals a variety of pharmacotherapies that induce echinocandin tolerance in <i>Candida albicans</i>.","authors":"Parker Reitler, Christian A DeJarnette, Ravinder Kumar, Katie M Tucker, Tracy L Peters, Nathaniel R Twarog, Anang A Shelat, Glen E Palmer","doi":"10.1128/aac.00484-25","DOIUrl":"10.1128/aac.00484-25","url":null,"abstract":"<p><p>Through screening a comprehensive collection of drugs approved for human use, we identified over 20 that oppose the antifungal activity of the echinocandins upon the infectious yeast, <i>Candida albicans</i>. More detailed evaluation of five such drugs, including the atypical antipsychotic aripiprazole and the tyrosine kinase inhibitor ponatinib, indicated they promote <i>C. albicans</i> survival following exposure to the echinocandin antifungals. The activity of the five selected antagonists was dependent upon the Mkc1p mitogen-activated protein kinase pathway; however, ponatinib was paradoxically shown to suppress phosphorylation and therefore activation of Mkc1p itself. Components of several other signaling pathways are also required, including those of calcineurin and casein kinase-2, suggesting the observed antagonism required much of the cell wall stress responses previously described for <i>C. albicans</i>. Transcriptome analysis revealed that the antagonists stimulated the expression of genes involved in xenobiotic and antifungal resistance and suppressed the expression of genes associated with hyphal growth. Thus, the echinocandin antagonistic drugs modulate <i>C. albicans</i> physiology in ways that could impact its pathogenicity and/or response to therapeutic intervention. Finally, a mutant lacking the Efg1p transcription factor, which has a central role in the activation of <i>C. albicans</i> hyphal growth, was found to have intrinsically high levels of echinocandin tolerance, suggesting a link between modulation of morphogenesis-related signaling and echinocandin tolerance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0048425"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871017","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":"Cytomegalovirus prophylaxis with letermovir in pediatric (birth to <18 years of age) hematopoietic cell transplant recipients: pharmacokinetics, efficacy, and safety results of a Phase 2b study.","authors":"Andreas H Groll, Lara Danziger-Isakov, Aharon Gefen, Christopher J Fraser, Johannes H Schulte, Bella Bielorai, Nicole A Karras, David Bueno, Peter J Shaw, Natalya Broyde, Barbara Haber, Christopher L Gilbert, Mayankbhai Patel, Jacqueline B McCrea, Cyrus Badshah","doi":"10.1128/aac.00420-25","DOIUrl":"10.1128/aac.00420-25","url":null,"abstract":"<p><p>Letermovir, a cytomegalovirus (CMV) terminase complex inhibitor, was first approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic cell transplant (HCT) recipients (R+). This study evaluated the pharmacokinetics (PK), efficacy, and safety of letermovir in pediatric R+ allogeneic HCT recipients. In this Phase 2b, single-arm, open-label study, 65 participants were enrolled sequentially in three age groups (AG; AG1, 12 to <18 years; AG2, 2 to <12 years; and AG3, birth to <2 years). PK was evaluated in an initial cohort in each AG using intensive PK data to confirm or modify dosing before enrolling the remaining participants. Adult HCT population PK (PopPK) data were used to establish the exposure reference range. The adult letermovir dose evaluated in AG1 and AG2 participants achieved exposures generally within the adult HCT reference range. In AG3, the initial cohort (letermovir with cyclosporin A) achieved exposures trending lower than the median exposure target; the letermovir dose was increased for the remaining participants. Efficacy and safety in pediatric participants were generally consistent with adult HCT data. A pediatric HCT PopPK model was developed to determine dose recommendations to be included in patient prescribing information. The doses evaluated achieved exposures generally within the adult HCT reference range. At exposures achieved, letermovir was efficacious and safe in preventing clinically significant CMV infection in pediatric allogeneic HCT recipients. The observed concentration data informed a pediatric PopPK model to optimize final letermovir dose recommendations in this population.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03940586.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0042025"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871018","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":"Exploring determinants in deciding the optimal antimicrobial dose in patients undergoing CRRT: a mixed-methods study.","authors":"Tuğba Yanık Yalçın, Aysel Pehlivanlı, Fatma İrem Yeşiler, Helin Şahintürk, Özlem Azap, Hande Arslan, Bilgen Başgut, Pınar Zeyneloğlu","doi":"10.1128/aac.00238-25","DOIUrl":"10.1128/aac.00238-25","url":null,"abstract":"<p><p>Antimicrobial dosing in patients undergoing continuous renal replacement therapy (CRRT) is a clinical challenge. The study aimed to investigate the factors that influence appropriate antimicrobial doses in CRRT and to address gaps in current knowledge and practice. The mixed-method design involved two phases. For the quantitative phase, infectious disease, intensive care, and clinical pharmacy professionals completed a questionnaire assessing demographics and practice details, as well as their knowledge, attitudes, and practices on antibiotic dosing in CRRT. In the qualitative phase, online focus groups were conducted using a question schedule based on the Theoretical Domains Framework to explore challenges and expectations. A structured questionnaire was completed by 160 participants, most of whom were infectious disease specialists (61.3%) with over 10 years of experience (38.8%). Despite a high knowledge level of antimicrobial dosing during CRRT, the sieving coefficient was unclear at 74.4%. Although 96.3% reported adjusting doses, 78.8% lacked institutional guidelines, and 68.1% did not monitor drug levels. CRRT experience positively influenced knowledge and attitude scores, and different dosing practices were reported for meropenem, piperacillin-tazobactam, and vancomycin. Qualitative findings highlighted the need for standard guidelines and CRRT-specific training. Multidisciplinary collaboration and real-time monitoring of therapeutic drugs were emphasized. This study identifies key gaps in knowledge and practice regarding antimicrobial dosing in CRRT. Addressing these gaps requires targeted training programs, real-time drug monitoring, and the development of evidence-based dosing guidelines to enhance patient safety and antimicrobial efficacy. Future research should evaluate the impact of these interventions on clinical outcomes.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0023825"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871019","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":"Cost-effectiveness of olorofim in the treatment of invasive aspergillosis in patients with limited suitable alternative treatment options: a US payer perspective.","authors":"Thomas J Walsh, Craig I Coleman, Rob Blissett, Thibaud Prawitz, Giuseppe Bonetti, Magda Aguiar, Mark Bresnik, Belinda Lovelace","doi":"10.1128/aac.00570-25","DOIUrl":"10.1128/aac.00570-25","url":null,"abstract":"<p><p>This study aimed to estimate the cost-effectiveness of treating invasive aspergillosis (IA) in patients with limited treatment options with either olorofim or currently available antifungal salvage therapy from a US payer perspective. A hybrid decision tree-Markov model with a one-year time horizon was used to estimate health economic outcomes. The model considered probabilities of treatment response, mortality, and treatment-emergent adverse events; costs of antifungals and healthcare utilization; and patient utility. For olorofim, patient-level data from the open-label, single-arm, Phase IIb study of olorofim for the treatment of proven or probable IA with limited treatment options (Study 32, NCT03583164) was used. Salvage therapy data were based on an external control arm of a study of IA patients. A willingness-to-pay threshold of $50,000/quality-adjusted life-year (QALY) was assumed to assess the cost-effectiveness of olorofim versus salvage therapy. One-year costs (2023 USD) of treating IA in patients with limited alternative options were $208,696 for currently available salvage therapy and $167,971 for olorofim, for an incremental cost reduction of $40,725. QALYs were 0.46 for olorofim and 0.22 for salvage therapy. Olorofim was determined to be a dominant (less costly, more effective) strategy, with an incremental net monetary benefit of $52,827. Olorofim remained the dominant strategy across all sensitivity analyses. Upon probabilistic sensitivity analysis, olorofim was dominant in 90.0% of 1,000 iterations and cost-effective in 97.5%. Olorofim resulted in lower total treatment costs, antifungal costs, and more QALY gains versus currently available salvage therapy, making olorofim the dominant strategy for treating IA with limited treatment options.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0057025"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940179","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":"Efficacy and <i>in vitro</i> activity of gepotidacin against bacterial uropathogens, including subsets with molecularly characterized resistance mechanisms and genotypes/epidemiological clones, in females with uncomplicated urinary tract infections: results from two global, pivotal, phase 3 trials (EAGLE-2 and EAGLE-3).","authors":"Nicole E Scangarella-Oman, Deborah L Butler, John Breton, Derrek Brown, Cara Kasapidis, Amanda J Sheets","doi":"10.1128/aac.01639-24","DOIUrl":"10.1128/aac.01639-24","url":null,"abstract":"<p><p>Gepotidacin, a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial, was noninferior to nitrofurantoin in two pivotal trials (EAGLE-2 and EAGLE-3) in females with uncomplicated urinary tract infections (uUTIs). Using pooled data, gepotidacin <i>in vitro</i> activity and clinical efficacy were evaluated for subsets of molecularly characterized isolates in the microbiological Intent-to-Treat population. The subsets of isolates were characterized based on phenotypic/MIC criteria; all microbiological failure isolates were also characterized. Of 1,159 <i>Escherichia coli</i> isolates<i>,</i> 30% harbored quinolone resistance-determining region (QRDR) mutations; most prevalent was <i>gyrA</i> S83L, D87N (27%). Extended-spectrum β-lactamases (ESBLs) were detected in 13% of <i>E. coli</i> isolates. For 114 <i>Klebsiella pneumoniae</i> isolates, 22% were plasmid-mediated quinolone resistance (PMQR) gene-positive, 11% had QRDR mutations, and 12% had ESBLs. Among 67 <i>Proteus mirabilis</i> isolates, 21% harbored QRDR mutations. Gepotidacin MIC₉₀ values ranged from 1 to 32 µg/mL against qualifying Enterobacterales uropathogens and genotypic subcategories, with no isolates considered resistant to gepotidacin. For all genotypic subcategories, gepotidacin MIC₉₀ values were similar (i.e., lower, equal to, or 1-dilution higher) compared with the overall species (4 µg/mL), with the exception of <i>E. coli</i> isolates with the PMQR <i>qnrS1</i> gene (16 µg/mL); all were gepotidacin-susceptible. For the majority of uropathogens, including those with genotypes likely to cause resistance to standard uUTI therapies, success rates for gepotidacin were similar across genotypic subcategories for each species. These data show gepotidacin's efficacy and <i>in vitro</i> activity against a wide range of uropathogen genotypes. Additionally, these pooled results provide a robust, contemporary data set and insight into current genotypic mechanisms of resistance.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04020341 and NCT04187144.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0163924"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022810","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":"<i>Burkholderia pseudomallei</i> PenI β-lactamase and variants are potently inhibited by taniborbactam.","authors":"Maria F Mojica, Scott A Becka, Mitchell Edwards, Cullen Myers, Kyoko Uehara, Tsuyoshi Uehara, Tyuji Hoshino, Elise T Zeiser, Cassandra L Chatwin, David A Six, Robert A Bonomo, Krisztina M Papp-Wallace, Michiyoshi Nukaga","doi":"10.1128/aac.00787-25","DOIUrl":"10.1128/aac.00787-25","url":null,"abstract":"<p><p><i>Burkholderia pseudomallei</i> is a Gram-negative pathogen that causes melioidosis, a severe and often fatal disease. Due to its recognized potential as a bioterrorism agent, it is critical that appropriate antimicrobial agents are available for post-exposure prophylaxis and treatment of melioidosis. Cefepime-taniborbactam is a novel β-lactam-β-lactamase inhibitor combination in clinical development, with promising activity against Gram-negative bacteria producing class A, B, C, and/or D β-lactamases. Herein, we demonstrate the inhibitory activity of taniborbactam against PenI, the class A β-lactamase produced by <i>B. pseudomallei</i>. Isogenic <i>Escherichia coli</i> strains producing PenI and its ceftazidime-resistance-conferring variants (C69Y and P167S) showed ceftazidime minimum inhibitory concentration (MIC) of 64 mg/L for the strain producing PenI and 1,024 mg/L for the strains producing the variants, whereas cefepime MIC was 128-256 mg/L for these three strains. While the addition of avibactam decreased ceftazidime MIC to 1 mg/L for PenI and 8-16 mg/L for the variants, the addition of taniborbactam decreased cefepime MIC to ≤0.5 mg/L for PenI and the variants. Similarly, an 8-fold reduction of the cefepime MIC upon addition of taniborbactam was observed in an avirulent <i>B. pseudomallei</i> strain. Furthermore, taniborbactam inhibited PenI and its C69Y variant with an apparent <i>K</i>_i of 0.11 and 3.1 µM, respectively. Lastly, co-crystallography and molecular dynamics simulations showed that taniborbactam induced the formation of a disulfide bond between Cys77 and Cys123, which destabilizes the deacylation water and strengthens the taniborbactam-PenI complex. These results support the development of cefepime-taniborbactam as a promising agent for the treatment of infections by <i>B. pseudomallei</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0078725"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038968","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":"Reply to Schön et al., \"Quality control and considering systematic MIC shifts are key when evaluating the role of <i>mmpR5</i> (<i>Rv0678</i>) frameshifts in bedaquiline resistance\".","authors":"J Snobre, C J Meehan, W Mulders, L Rigouts, R Buyl, B C de Jong, A Van Rie, O Tzfadia","doi":"10.1128/aac.00317-25","DOIUrl":"10.1128/aac.00317-25","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0031725"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854332","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":"Safety, pharmacokinetics, and pharmacodynamics of human interferon-α2b spray in healthy participants.","authors":"Wen-Rui Zhang, Wei-Zhe Jian, Yong-Xing Chen, Yue-Yuan Huang, Tian-Yan Zhou, Xiao-Qing Wen, Xi Luo","doi":"10.1128/aac.00686-25","DOIUrl":"10.1128/aac.00686-25","url":null,"abstract":"<p><p>The safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of human interferon (IFN)-α2b spray administered via nasal and oropharyngeal routes were evaluated in a randomized, double-blind, placebo-controlled study. Forty-eight healthy Chinese participants were randomized into three dose groups: low (450,000 IU/dose), medium (600,000 IU/dose), and high (750,000 IU/dose). In each group, 12 participants received the corresponding dose of IFN-α2b spray, and four participants received the placebo. All participants received a single nasal and oropharyngeal dose at 0 and 48 h, respectively, with the high-dose group receiving an additional topical abdominal skin dose at 96 h to assess skin irritation. Adverse events were observed and recorded throughout the trial. Plasma, nasal lavage fluid, and oral gargle samples were collected, with IFN concentration and interferon-inducible protein-10 level being determined as PK and PD indicators, respectively. The results suggest that IFN-α2b spray was safe and well-tolerated across all doses (450,000-750,000 IU) with no systemic exposure detected. PK/PD analysis showed a correlation between the PD index and the level of IFN exposure in nasal lavage fluid, while no significant correlation was observed in oral gargle samples. The IFN concentrations in all dose groups were higher than the half-maximal effective dose (ED₅₀), suggesting that the high dose could be considered for subsequent clinical trials.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0068625"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854333","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":"Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of <i>Plasmodium falciparum</i>.","authors":"Vella Nikolova, Karen Linnemannstöns, Anastasiia Zahoruiko, Markus Ganter, Carsten G Lüder, Matthias Dobbelstein","doi":"10.1128/aac.00471-25","DOIUrl":"10.1128/aac.00471-25","url":null,"abstract":"<p><p>Malaria tropica, caused by <i>Plasmodium falciparum</i> (<i>P. falciparum</i>), remains a global health challenge with limited therapeutic options. In mammalian cells, the small-molecule compound RAS-selective lethal 3 (RSL3) induces ferroptosis via lipid peroxidation. In this study, we demonstrate that RSL3 synergizes with Pyrimethamine, an inhibitor of <i>P. falciparum</i> dihydrofolate reductase (DHFR), to suppress parasite proliferation in red blood cells (RBCs). A similar synergistic effect was observed with Cycloguanil, a structural analog of Pyrimethamine, but not with other DHFR inhibitors or alternative agents that induce ferroptosis in nucleated mammalian cells. Notably, Ferrostatin-1, an antagonist of lipid peroxidation, largely failed to rescue parasite growth in the presence of RSL3, possibly suggesting a mechanism distinct from canonical ferroptosis. These findings suggest that the synergy may involve unidentified targets of RSL3 and Pyrimethamine in <i>P. falciparum</i>, divergent from those described in mammalian systems. Moreover, RSL3 and related compounds could serve as promising adjuvants to enhance the antimalarial efficacy of Pyrimethamine and potentially overcome drug resistance.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0047125"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871047","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":"Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence.","authors":"Burcu Isler, Zhenya Welyczko, Nicholas Jorgensen, Joshua Davis, David L Paterson","doi":"10.1128/aac.00338-25","DOIUrl":"10.1128/aac.00338-25","url":null,"abstract":"<p><p>Prosthetic joint infections (PJI) remain among the most devastating complications in orthopedic surgery, with increasing incidence paralleling the growth in arthroplasty procedures worldwide. While treatment protocols are well-established, evidence supporting current approaches is lacking, and outcomes remain suboptimal, highlighting the need for improved therapeutic strategies. The objective of this study is to review ongoing and recently completed randomized controlled trials (RCTs) investigating novel approaches to PJI prevention and treatment. We searched PubMed and ClinicalTrials.gov databases for RCTs that focused on PJI management, and that are ongoing or completed within the 6 months preceding February 28, 2025. We included investigator-initiated trials, studies of novel therapeutic agents, and studies on infection prevention strategies. We extracted and reviewed data regarding trial design, interventions, and outcomes. We identified significant advances in three key areas: (i) investigator-initiated trials exploring optimization of current surgical and antimicrobial treatment strategies, including the ROADMAP adaptive platform trial (ii); novel therapeutic agents, including engineered antibacterial peptides, monoclonal antibodies, and new-generation antibiotics specifically targeting biofilm-associated infections; and (iii) prevention strategies, particularly focusing on perioperative antibiotic protocols. Recent trials demonstrate promising approaches to reducing antibiotic exposure while maintaining efficacy, novel mechanisms for biofilm disruption, and strategies for optimizing perioperative prophylaxis. Investigator-initiated trials like ROADMAP and SOLARIO are challenging traditional paradigms, particularly in antibiotic duration, while novel therapeutics targeting biofilm through various mechanisms show promise in early-phase trials. Future research should prioritize cost-effectiveness analyses, targeted studies for specific patient subgroups, and evaluation of combination therapeutic approaches.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0033825"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854329","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}