Antimicrobial Agents and Chemotherapy最新文献

{"title":"Synergistic combination of next-generation polymyxin MRX-8 and meropenem against carbapenem-resistant <i>A. baumannii</i>.","authors":"Xiaofen Liu, Xingyi Qu, Ruohao Zhang, Yuxin Zhang, Xingchen Bian, Yu-Wei Lin, Jing Zhang","doi":"10.1128/aac.01912-24","DOIUrl":"https://doi.org/10.1128/aac.01912-24","url":null,"abstract":"<p><p>MRX-8 is a new next-generation polymyxin with potent antibacterial activity against carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB). This study evaluated the MRX-8 and meropenem combination and their dosing regimens against CRAB in clinics. Seven CRAB strains isolated from Huashan Hospital were tested. Two strains of AB21-3881 and AB21-3759 were selected for static time-kill and the Hollow Fiber Infection Model (HFIM). Adaptive resistance to MRX-8 was assessed via population analysis profiling (PAP) at 2 mg/L of MRX-8. Multilocus sequence typing identified all seven strains as ST2. Minimum inhibitory concentration values for MRX-8 ranged from 0.5 to 1 mg/L. Synergy was observed in six out of seven (85.7%) strains. The combination of 1 mg/L MRX-8 with 1 mg/L meropenem completely inhibited bacterial growth within 24 h for both selected strains. In HFIM, the combination of MRX-8 (0.75 mg/kg q8h continuous infusion) and meropenem (1 g q6h continuous infusion) achieved synergistic killing over 72 h for AB21-3759, while single treatment of MRX-8 (0.75 mg/kg q8h continuous infusion) achieved bactericidal effect (lower than the detect limitation) over 72 h. PAP analysis demonstrated that the combinational therapy could delay the emergence of adaptive resistance sub-populations by 12-24 h. The combination of MRX-8 and meropenem demonstrated synergistic bactericidal activity by checkerboard and static time-kill curves. Additionally, in HFIM, MRX-8 at 1 mg/kg q12h combined with meropenem at 2 g q12h, as well as MRX-8 at 0.75 mg/kg q8h continuous infusion combined with meropenem at 1 g q6h continuous infusion, achieved bacteriostatic killing at 72 h compared to the initial inoculum.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0191224"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148901","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":"SAND: a comprehensive annotation of class D β-lactamases using structural alignment-based numbering.","authors":"Fedaa Attana, Soobin Kim, James Spencer, Bogdan I Iorga, Jean-Denis Docquier, Gian Maria Rossolini, Mariagrazia Perilli, Gianfranco Amicosante, Alejandro J Vila, Sergei B Vakulenko, Shahriar Mobashery, Patricia Bradford, Karen Bush, Sally R Partridge, Andrea M Hujer, Kristine M Hujer, Robert A Bonomo, Shozeb Haider","doi":"10.1128/aac.00150-25","DOIUrl":"https://doi.org/10.1128/aac.00150-25","url":null,"abstract":"<p><p>Class D β-lactamases are a diverse group of enzymes that contribute to antibiotic resistance by inactivating β-lactam antibiotics. Examination of class D β-lactamases has evolved significantly over the years, with advancements in molecular biology and structural analysis providing deeper insights into their mechanisms of action and variation in specificity. However, one of the challenges in the field is the inconsistent residue numbering and secondary structure annotation across different studies, which complicates the comparison and interpretation of data. To address this, we propose SAND-a standardized naming system for both residues and secondary structure elements, based on a comprehensive structural alignment of all documented sequences and experimentally obtained crystal structures of class D β-lactamases. This unified framework will streamline cross-study comparisons and enhance data interpretation. Moreover, the standardized framework will enable AI-driven natural language processing (NLP) techniques to efficiently mine and compile relevant data from scientific literature, speeding up the discovery process and contributing to more rapid advancements in β-lactamase research.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0015025"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148894","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":"Functional and structural analyses of amino acid sequence variation in PDC β-lactamase reveal different mechanistic pathways toward cefiderocol resistance in <i>Pseudomonas aeruginosa</i>.","authors":"Lucía González-Pinto, María Antonia Gomis-Font, Emilio Lence, Michelle Outeda-García, Tania Blanco-Martín, Salud Rodríguez-Pallares, Lucía Sánchez-Peña, Isaac Alonso-García, Juan Carlos Vázquez-Ucha, Alejandro Beceiro, Germán Bou, Concepción González-Bello, Antonio Oliver, Jorge Arca-Suárez","doi":"10.1128/aac.00292-25","DOIUrl":"https://doi.org/10.1128/aac.00292-25","url":null,"abstract":"<p><p>A wide variety of clinically observed amino acid alterations in the <i>Pseudomonas aeruginosa</i> chromosomal β-lactamase AmpC (<i>Pseudomonas</i>-derived cephalosporinase [PDC]) are associated with increased resistance to cefepime, ceftolozane/tazobactam, or ceftazidime/avibactam, but their impact on cefiderocol resistance is unclear. We took advantage of a previously engineered collection of wild-type (PAO1) and iron uptake-deficient (PAO Δ<i>piuC</i>) <i>P. aeruginosa</i> isolates producing 19 distinct PDC variants with substitutions in key catalytic regions. While most variants had moderate effects on cefiderocol minimum inhibitory concentrations compared to PDC-1, the E219K (Ω-loop) and L293P (helix H10) variants significantly affected cefiderocol activity. Kinetic studies revealed that both mutations improve cefiderocol hydrolysis through different enzymatic mechanisms compared to PDC-1 (<i>K</i>_m = 85.29 µM, <i>k</i>_cat = 0.0036 s^-1, and <i>k</i>_cat/<i>K</i>_m = 0.00004 µM^-1 s^-1), leading to enhanced turnover in PDC E219K (<i>K</i>_m = 465.64 µM, <i>k</i>_cat = 0.45 s^-1, and <i>k</i>_cat/<i>K</i>_m = 0.00096 µM^-1 s^-1) and improved affinity in PDC L293P (<i>K</i>_m = 2.69 µM, <i>k</i>_cat = 0.0036 s^-1, and <i>k</i>_cat/<i>K</i>_m = 0.00135 µM^-1 s^-1). These mechanisms are also involved in resistance to ceftolozane and cefepime, identified as the preferred substrates for the E219K and L293P variants, respectively. Molecular dynamics (MD) simulation studies revealed that (i) rigidification of the Ω-loop in PDC E219K promotes optimal accommodation of the R¹ group of cefiderocol, enhancing nucleophilic attack by the catalytic serine; (ii) the less folded conformation of helix H10 in PDC L293P improves cefiderocol accommodation in the active site by establishing stronger hydrogen-bonding interactions with the R² group. Our findings demonstrate that the PDC β-lactamase may take advantage of the structural similarities between cefiderocol and other cephalosporins and accelerate hydrolysis by accommodating the E219K or L293P amino acid replacements.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0029225"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149065","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":"The PfK13 G533S mutation confers artemisinin partial resistance in multiple genetic backgrounds of <i>Plasmodium falciparum</i>.","authors":"Faiza Amber Siddiqui, Aongruk Chim-Ong, Chenqi Wang, Jun Miao, Liwang Cui","doi":"10.1128/aac.00162-25","DOIUrl":"https://doi.org/10.1128/aac.00162-25","url":null,"abstract":"<p><p>Mutations in the <i>Plasmodium falciparum</i> Kelch 13 (PfK13) protein are the key determinant of artemisinin partial resistance. While more than 200 PfK13 mutations have been identified in global parasite populations, only 13 have been validated to confer <i>in vivo</i> or <i>in vitro</i> artemisinin partial resistance. In the western Greater Mekong Subregion, the prevalence of the PfK13 G533S mutation has significantly increased in recent years. Field isolates carrying the PfK13 G533S mutation showed slower parasite clearance and higher day-3 positivity rates after artemisinin treatment, while culture-adapted isolates displayed significantly elevated ring-stage survival rates. Here, the PfK13 G533S mutation was introduced using CRISPR/Cas9 into four parasite strains: Dd2, 3D7, GB4, and F09N25 (a recent culture-adapted field isolate from the China-Myanmar border area). Across all four genetic backgrounds, the PfK13 G533S mutation conferred ring-stage survival rates of 12%-23% with a minimal fitness cost, explaining its rising prevalence in the region. In contrast, the PfK13 G533A mutation, sporadically detected in world <i>P. falciparum</i> populations, did not increase ring-stage survival rates when engineered into the 3D7 and Dd2 strains. These findings validate the <i>PfK13</i> G533S mutation as a critical marker for artemisinin resistance surveillance and underscore the importance of monitoring its spread.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0016225"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148906","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":"High-throughput screening of small molecules targeting <i>Mycobacterium tuberculosis</i> in human iPSC macrophages.","authors":"Alejandro Armesilla-Diaz, María Pilar Arenaz, Charlotte Ashby, Delia Blanco, Emiliana D'Oria, Helena Garuti, Vanesa Gómez, Rubén González-Del-Río, María Martínez-Hoyos, Eugenia Meiler, Alfonso Mendoza-Losana, Lisa Mohamet, Laura Padrón-Barthe, Esther Pérez, Laura Pérez, Modesto J Remuiñán, Beatriz Rodríguez-Miquel, Delfina Segura-Carro, Sara Viera-Morilla","doi":"10.1128/aac.01613-24","DOIUrl":"https://doi.org/10.1128/aac.01613-24","url":null,"abstract":"<p><p>New treatments are still necessary to eradicate tuberculosis disease. Macrophages derived from human induced pluripotent stem cells (hiPSC-Macs) offer a physiological niche to identify potential new drugs in the context of <i>Mycobacterium tuberculosis</i> (Mtb) infection. Here, we describe the scale-up of hiPSC-Macs production in 5-stack chambers for high-throughput drug screening against Mtb. A rate of approximately 100 million hiPSC-Macs was generated with optimal quality for a period of up to 12 weeks. Moreover, the infection model was optimized using a luminescence-based Mtb reporter strain. The assay showed enough sensitivity to identify compounds that could target host-pathogen interactions during Mtb infection. We interrogated a library of 200,000 compounds in Mtb-infected hiPSC-Macs with a Z-score above 0.3 in all plates analyzed. After secondary assays, 223 qualified hits were selected for further progression.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0161324"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148883","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":"Limited predictive power of known resistance genes for phenotypic drug resistance in clinical <i>Mycobacterium abscessus</i> complex from Beijing in China.","authors":"Yue Hou, Rui Pi, Junnan Jia, Zhaojun Wu, Fengmin Huo, Yu Zhou, Hui Jiang, Howard E Takiff, Chendi Zhu, Wei Wang, Weimin Li","doi":"10.1128/aac.01847-24","DOIUrl":"https://doi.org/10.1128/aac.01847-24","url":null,"abstract":"<p><p><i>Mycobacterium abscessus</i> complex (MABC) is an emerging pathogen with intrinsic multidrug resistance. Genomic sequencing technology has been widely applied to predict bacterial resistance in other bacteria, but the catalog of known resistance-determining genes to explain phenotypic resistance in the MABC is incomplete for many antibiotics. Eighty-one MABC strains were isolated from sputum samples of patients with pulmonary disease in the Beijing Chest Hospital. All isolates were tested for minimum inhibitory concentrations (MICs) to eight antibiotics and underwent whole-genome sequencing (WGS). Of the total 81 MABC isolates, six strains exhibited clarithromycin (CLM) resistance by day 3 in culture, but only one (16.7%, 1/6) contained a mutation in the <i>rrl</i> gene. All <i>M. abscessus</i> strains contained the <i>erm (41)28T</i> (100.0%, 49/49) polymorphism and exhibited CLM-induced resistance after 14 days in culture. Of the 61 imipenem-resistant strains, 12 (19.7%, 12/61) had mutations in the <i>bla</i> gene. Although there were four (4.9%) amikacin-resistant, nine (11.1%) linezolid-resistant, eight (9.9%) clofazimine-resistant, 23 (28.4%) bedaquiline-resistant, and 27 (33.3%) cefoxitin-resistant strains, no known mutations associated with resistance to these antibiotics were found. These results suggest that the explanatory power of known resistance genes for clinical MABC resistance is limited and that other unidentified genes or novel resistance mechanisms may be involved.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0184724"},"PeriodicalIF":4.1,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148888","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":"Contribution of RND superfamily multidrug efflux pumps AdeABC, AdeFGH, and AdeIJK to antimicrobial resistance and virulence factors in multidrug-resistant <i>Acinetobacter baumannii</i> AYE.","authors":"Lulin Xie, Junwei Li, Qin Peng, Xianqing Liu, Fei Lin, Xiaozhen Dai, Baodong Ling","doi":"10.1128/aac.01858-24","DOIUrl":"https://doi.org/10.1128/aac.01858-24","url":null,"abstract":"<p><p><i>Acinetobacter baumannii</i> is a critical priority gram-negative bacterial species characterized by multidrug resistance. The latter is significantly attributable to the resistance-nodulation-cell division (RND) superfamily of tripartite multidrug efflux systems represented by AdeABC, AdeFGH, and AdeIJK. By constructing isogenic deletion mutants, this investigation assessed the impact of RND efflux pumps on planktonic and biofilm cell antimicrobial susceptibility as well as on biofilm formation and virulence factors in a multidrug-resistant reference strain, <i>A. baumannii</i> AYE. Inactivation of individual genes encoding the aforementioned three RND pumps or regulators (i.e., AYE△<i>adeA</i>, △<i>adeB</i>, △<i>adeC</i>, △<i>adeRS</i>, △<i>adeFGH</i>, and △<i>adeIJK</i> mutants) demonstrated that the three efflux pumps, particularly AdeB, contribute to resistance in both planktonic and biofilm cells to structurally unrelated anti-<i>A</i>. <i>baumannii</i> drugs, including carbapenems, fluoroquinolones, macrolides, polymyxins, and/or tetracyclines/tigecycline. The pump inactivation also altered other functions, changes in bacterial motility and adhesion, reduction of biofilm formation, and decreased expression of the genes related to biofilm formation and virulence factors (<i>abaI</i>, <i>bap, bfmR</i>, <i>csuE</i>, <i>ompA,</i> and <i>pgaA</i>, except for <i>abaR</i> whose expression was increased). The virulence assay measured through the survival rates of <i>A. baumannii</i>-infected <i>Galleria mellonella</i> revealed the relation between RND pumps (particularly AdeB) and pathogenicity. The findings together expand the understanding of specific <i>A. baumannii</i> RND pumps or components for their roles in resistance and virulence/pathogenicity in the presence of high-level multidrug resistance, highlighting the RND pumps as potential therapeutic intervention targets against <i>A. baumannii</i> infection.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0185824"},"PeriodicalIF":4.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126171","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":"An enoyl-ACP reductase inhibitor, NITD-916, expresses anti-<i>Mycobacterium abscessus</i> activity.","authors":"Yaping Jia, Junsheng Fan, Zhili Tan, Anqi Li, Siyuan He, Yani Lin, Juan Li, Zhemin Zhang, Bing Li, Haiqing Chu","doi":"10.1128/aac.00249-25","DOIUrl":"https://doi.org/10.1128/aac.00249-25","url":null,"abstract":"<p><p>Antibiotic therapy for <i>Mycobacterium abscessus</i> infections is challenging due to resistance of the organism to many clinically available antimicrobials. Here, the efficacy of NITD-916, an enoyl-ACP reductase inhibitor, in preventing <i>M. abscessus</i> growth <i>in vitro</i> and <i>in vivo</i> is demonstrated. The minimal inhibitory concentrations (MICs) of NITD-916 for 12 non-tuberculosis mycobacteria (NTM) reference strains and a collection of 194 clinical <i>M. abscessus</i> isolates were determined using the broth microdilution method. Compatibility of NITD-916 with 10 clinically important antibiotics was ascertained by checkerboard assay. The activity of NITD-916 against <i>M. abscessus</i> growing in cultured macrophages was also evaluated. Finally, the potency of NITD-916 <i>in vivo</i> was determined in a mouse model that mimicked an acute pulmonary <i>M. abscessus</i> infection. NITD-916 was bacteriostatic for <i>M. abscessus</i> replicating <i>in vitro,</i> expressing a MIC₅₀ of 0.125 mg/L and a MIC₉₀ of 1 mg/L against the screened clinical isolates. Furthermore, NITD-916 synergized with clarithromycin in treating 2 out of 5 subsp. <i>massiliense</i> strains. NITD-916 was active against <i>M. abscessus</i> replicating in both cultured macrophages and infected mice. The administration of 100 mg/kg NITD-916 for 14 days resulted in a 5.6 log₁₀ colony-forming units (CFUs) reduction in the bacterial load in mouse lung tissue. NITD-916 is active against <i>M. abscessus in vitro</i> and <i>in vivo</i> and may be used potentially to treat <i>M. abscessus</i> diseases.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0024925"},"PeriodicalIF":4.1,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126169","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":"Correction for Nelson et al., \"Pbp4 provides transpeptidase activity to the FtsW-PbpB peptidoglycan synthase to drive cephalosporin resistance in <i>Enterococcus faecalis</i>\".","authors":"Madison E Nelson, Jaime L Little, Christopher J Kristich","doi":"10.1128/aac.00594-25","DOIUrl":"https://doi.org/10.1128/aac.00594-25","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0059425"},"PeriodicalIF":4.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109114","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":"Impact of an electronic antibiotic time-out best practice alert on antibiotic use and prescribing behavior in hospitalized patients.","authors":"Tyler Ackley, Joseph Kuti, Anastasia Bilinskaya, Kristin Linder, Casey Dempsey","doi":"10.1128/aac.01680-24","DOIUrl":"https://doi.org/10.1128/aac.01680-24","url":null,"abstract":"<p><p>Provider-directed electronic antibiotic time-outs (ATOs) are a stewardship strategy capable of efficient and widespread impact with relatively low perceived personnel effort. This is a multi-center, quasi-experimental, retrospective chart review of patients admitted receiving empiric antibiotics for >72 hours. An ATO alert was designed and embedded within the electronic medical record and set to fire between the hours of 07:00 and 16:30 daily. Seventy-two hours after a unique antibiotic order was entered, a best practice alert (BPA) would fire for the primary team-including the attending physician, residents, and advanced practice providers-as well as any infectious disease provider consulted at the time of ATO firing. This alert is triggered when entering or modifying orders as an active pop-up to the ordering prescriber. Prescribers were then prompted to assess the patient for potential antibiotic optimization-including discontinuation, de-escalation, and transition to oral therapies. A total of 800 patients receiving >72 hours of antibiotics were included for analysis. There was no statistically significant difference in the rate of antibiotic optimization when comparing the pre- and post-implementation cohort (54.5% vs 57.5%, <i>P</i> = 0.433); however, there was a numerically lower rate of antibiotic escalation in the post-cohort (9.5% vs 5.8%, <i>P</i> = 0.062). Duration of antibiotic therapy was longer in the post-implementation cohort (4.7 vs 5.0 days, <i>P</i> < 0.001). The implementation of an ATO BPA failed to improve the rates of antibiotic optimization.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0168024"},"PeriodicalIF":4.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109306","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}