Antimicrobial Agents and Chemotherapy最新文献

{"title":"Amphotericin B resistance in <i>Lomentospora prolificans</i> is associated with a soluble cell wall component.","authors":"Nina T Grossman, Arturo Casadevall","doi":"10.1128/aac.00915-26","DOIUrl":"10.1128/aac.00915-26","url":null,"abstract":"<p><p><i>Lomentospora prolificans</i> is a pathogenic filamentous fungus that causes disease primarily in people with severely compromised immune systems. It is pan-resistant to antifungal drugs, but the mechanism of its resistance to amphotericin B (AMB) is unknown. In this study, our goal was to investigate the mechanism of resistance to AMB of <i>L. prolificans</i>. The AMB susceptibility of <i>L. prolificans</i> protoplasts were measured using broth microdilution. <i>L. prolificans</i>, either intact, homogenized, or fractionated, was incubated with AMB in broth. The same activity was carried out with <i>Aspergillus fumigatus</i> as a control. These broths were then used to prepare microdilution plates with <i>Saccharomyces cerevisiae</i> to determine the activity of the conditioned AMB. AMB was 16-fold more effective at inhibiting the growth of <i>L. prolificans</i> protoplasts than conidia, but only 2-fold more effective against <i>A. fumigatus</i> protoplasts than conidia. Incubation of <i>L. prolificans</i> hyphae with AMB in media diminished drug activity to a much greater extent than <i>A. fumigatus</i>, with an 8-fold greater fungal mass of the latter required to achieve the effect of the former. Homogenization and fractionation of <i>L. prolificans</i> revealed that the factor inhibiting AMB activity was soluble with a mass >100 kDa. DNase, trypsin, proteinase K, amyloglucosidase, SDS, and 0.22 μm filtration had no effect on the AMB resistance factor, while treatment with urea and acetonitrile inactivated it. In summary, we report a different mechanism for AMB resistance for <i>L. prolificans</i> based on the existence of a substance residing in the cell wall that can eliminate the antifungal activity of AMB.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0091526"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982140","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":"N-terminal lysine as a critical determinant of odilorhabdin susceptibility to inactivation by the self-resistance acetyltransferase OatA.","authors":"Emilie Racine, Anne Lanois-Nouri, Jessica Houard, Lucile Pantel, Alain Givaudan, Maxime Gualtieri","doi":"10.1128/aac.00743-26","DOIUrl":"10.1128/aac.00743-26","url":null,"abstract":"<p><p>Odilorhabdins (ODLs) are a novel class of peptide antibiotics that inhibit bacterial translation by binding to the 30S ribosomal subunit. <i>Xenorhabdus nematophila</i>, an ODL-producing bacterium, encodes a highly specialized self-resistance acetyltransferase, OatA, that inactivates ODLs via primary amine modification. In this study, we investigated the structural determinants governing susceptibility of the natural compound NOSO-95C to OatA-mediated inactivation. Using an alanine-scanning library, we identified <i>N</i>-terminal lysine (Lys₁) as the key structural determinant of acetyltransferase susceptibility. Expression of <i>oatA</i> in <i>E. coli</i> increased the MIC of NOSO-95C by 64-fold due to rapid OatA-mediated acetylation. In contrast, analog <b>1</b> (Lys1→Ala) was no longer discriminated between Oat-A expressing and non-expressing strains, and remained 95.4% unacetylated after 4 h of incubation. Functional assays confirmed that analog <b>1</b> retains potent translation inhibition and antibacterial activity despite enzyme exposure. Furthermore, OatA failed to inactivate other amine-containing clinical antibiotics such as aminoglycosides, penicillin, or polymyxins. These results indicate that the side chain of <i>N</i>-terminal lysine is essential for efficient OatA-mediated acetylation of ODLs. Moreover, this single residue can be modified to enable ODLs to evade enzymatic inactivation while preserving their primary mechanism of action. This work provides a clear structure-activity framework for the rational design of next-generation ODLs with enhanced stability against OatA-mediated enzymatic modification.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0074326"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982173","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>Escherichia coli</i> with penicillin-binding protein 3 insertions: implications for newer β-lactam/β-lactamase inhibitor combinations.","authors":"Johann D D Pitout, Gisele Peirano, Yasufumi Matsumura, Marleen Kock, Liang Chen","doi":"10.1128/aac.01077-26","DOIUrl":"10.1128/aac.01077-26","url":null,"abstract":"<p><p><i>Escherichia coli</i> with penicillin-binding protein 3 (PBP3) insertions appeared in the early 2000s and expanded during the 2010s. The YRIN and YRIK variants predominate globally, while other insertion types remain rare. These insertions frequently co-occur with carbapenemases (NDM-5 and OXA-181) and high-risk clones (ST410, ST167, and ST405), contributing to the evolution and dissemination of multidrug resistance. Newer β-lactam/β-lactamase inhibitor combinations (ceftazidime/avibactam, aztreonam/avibactam, and cefepime/taniborbactam) and cefiderocol with affinities for PBP3 show reduced activity against <i>E. coli</i> with YRIN and YRIK insertions. The continued spread of such strains threatens the effectiveness of these β-lactam agents. In contrast, agents targeting PBP2, such as cefepime/zidebactam and cefiderocol-xeruborbactam, retain potent <i>in vitro</i> activity and will likely be important for future treatment strategies. Laboratory methods to detect PBP3 insertions are lacking, raising concern that these strains may be spreading largely undetected. Current surveillance efforts are insufficient, leaving significant gaps in data describing the global distribution and prevalence of <i>E. coli</i> with PBP3 insertions. The convergence of β-lactamase production and PBP target modification represents a paradigm shift within <i>E. coli</i> toward multidrug resistance. This occurrence provides a major barrier to current and future β-lactam/β-lactamase inhibitor development. There is an urgent need for enhanced global surveillance, along with rapid diagnostic tools capable of identifying PBP3 insertions and associated high-risk clones among carbapenemase-producing <i>E. coli</i>. Future strategies should prioritize agents with activities against multiple essential PBPs to preserve β-lactam efficacy.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0107726"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975504","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>In vitro</i> activity of gepotidacin against baseline <i>Neisseria gonorrhoeae</i> phenotypes and genotypes recovered from a clinical trial for uncomplicated urogenital gonorrhea (EAGLE-1).","authors":"Charles Jakielaszek, William Flight, Dan Lythgoe, Caroline Perry, Nicole E Scangarella-Oman","doi":"10.1128/aac.00752-26","DOIUrl":"https://doi.org/10.1128/aac.00752-26","url":null,"abstract":"<p><p>There is an urgent need for novel antimicrobials to treat multidrug-resistant strains of <i>Neisseria gonorrhoeae</i>. In a phase III trial (EAGLE-1), gepotidacin, a first-in-class triazaacenaphthylene antibacterial, demonstrated non-inferiority to ceftriaxone plus azithromycin as measured by microbiological success for the treatment of uncomplicated urogenital gonorrhea. Here, we assessed the <i>in vitro</i> activity of gepotidacin against key <i>N. gonorrhoeae</i> drug-resistant phenotypes and genotypes from EAGLE-1. There were 408 baseline urogenital isolates recovered from 406 patients during the EAGLE-1 study. Agar dilution minimum inhibitory concentration (MIC) susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines, and all isolates were molecularly characterized. All of the isolates were susceptible to ceftriaxone. All isolates had gepotidacin MICs of ≤2 µg/mL, with values ranging from ≤0.06 to 2 µg/mL; MIC₅₀, 0.25 µg/mL, and MIC₉₀, 0.5 µg/mL. As defined by the Food and Drug Administration (FDA) breakpoints and interpretive criteria (MIC breakpoints of ≤1 µg/mL [susceptible]; 2 µg/mL [intermediate]; and ≥4 µg/mL [resistant]), 99% of the study isolates were susceptible to gepotidacin, 1% were intermediate, and no isolates were resistant. Susceptibility percentages remained high across resistance phenotypes and genotypes. These findings support the <i>in vitro</i> activity of gepotidacin against the <i>N. gonorrhoeae</i> isolates, including drug-resistant phenotypes and genotypes, recovered in the EAGLE-1 clinical study.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04010539.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0075226"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126437","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>In vitro</i> activity of zosurabalpin against a global set of carbapenem-resistant-<i>A. baumannii</i> clinical isolates.","authors":"Stefano Mancini, Helena M B Seth-Smith, Klara Haldimann, Jacob Moran-Gilad, Elif Aktas, Öznur Güneş, Mohammedaman Mama Hussen, Mark Willcox, Shakeel Shahzad, Muhammad Ali Syed, Natalia Kolesnik-Goldmann, Tim Roloff, Oliver Nolte, Adrian Egli","doi":"10.1128/aac.00727-26","DOIUrl":"10.1128/aac.00727-26","url":null,"abstract":"<p><p>The limited treatment options for carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB)-invasive infections highlight the urgent need for novel therapeutic agents. Zosurabalpin is a first-in-class tethered macrocyclic-peptide targeting the LptB₂FGC-complex. In this study, we evaluated the <i>in vitro</i> activity of zosurabalpin a1gainst a diverse global set of CRAB clinical isolates. We compared zosurabalpin's activity with currently available antibiotics, including colistin, cefiderocol, sulbactam-durlobactam, as well as rifabutin. Additionally, we assessed different AST methods to support reliable zosurabalpin susceptibility testing. We included a total of 304 CRAB clinical isolates from Switzerland, Israel, Turkey, Ethiopia, Pakistan, and Australia. Among them, 297 carried plasmid-borne-carbapenemases (236 OXA-type-producers, 60 NDM-type-producers alone or in combination with OXA-type-carbapenemases, and 1 GES-14-producer), 3 were GES-ESBL-producers, and 4 isolates were without acquired ESBL/carbapenemases. We determined zosurabalpin minimal inhibitory concentrations (MICs) by broth microdilution using cation-adjusted Mueller-Hinton broth (CA-MHB) supplemented with 20% heat-inactivated horse serum, in accordance with CLSI recommendations, as well as using plain CA-MHB, with reading at substantial reduction (80% growth inhibition). We determined MICs of the remaining antibiotics according to EUCAST methods: colistin and sulbactam-durlobactam (with fixed durlobactam concentration of 4 mg/L) with CA-MHB, cefiderocol with iron-depleted CA-MHB, and rifabutin with RPMI. The zosurabalpin MIC distribution using the CLSI-based method ranged from ≤0.032 to 2 mg/L (MIC₉₀ = 0.5 mg/L), with no CRAB isolates showing MICs displaying MICs suggestive of high-level acquired resistance. A single isolate with MIC = 2 mg/L harbored a 13-amino-acid deletion in <i>lptD</i> (position 692), potentially affecting outer-membrane LPS biogenesis. MIC₉₀ values for cefiderocol, sulbactam-durlobactam, colistin, and rifabutin were 8, 16, 1, and 2 mg/L, respectively. Zosurabalpin showed no cross-resistance with any of the tested antimicrobials. Zosurabalpin MICs in CRAB isolates were generally low, including metallo-β-lactamase-producing-CRAB. The low MICs show a high potential to overcome current treatment limitations; however, mutations in <i>lptD</i> may contribute to resistance emergence and should be further studied.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0072726"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982199","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":"XAB06, a glyco-humanized broad-spectrum anti-<i>Pseudomonas aeruginosa</i> polyclonal antibody, protects mice in a lethal sepsis model.","authors":"Pierre-Joseph Royer, George Graur, Mehdi Varin, Bernard Vanhove, Odile Duvaux, Firas Bassissi","doi":"10.1128/aac.00277-26","DOIUrl":"10.1128/aac.00277-26","url":null,"abstract":"<p><p>The global rise of antibiotic-resistant <i>Pseudomonas aeruginosa</i> (PA) necessitates the development of novel therapeutic approaches. Polyclonal antibodies constitute a promising approach, as they target multiple bacterial epitopes and functions. Moreover, they have recently demonstrated renewed clinical applicability in their humanized format. We developed a glyco-humanized polyclonal antibody (GH-pAb) targeting PA by immunization of pigs with five PA serotypes frequently encountered in clinical settings. This pentavalent GH-pAb, named XAB06, exhibited binding activity against the five serotypes used for the immunization, as well as unrelated PA serotypes. No binding activity was observed against <i>Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae,</i> or <i>Acinetobacter baumannii</i>, demonstrating the specificity of XAB06 against PA. In addition, XAB06 showed no reactivity against human blood cells. Functional assays revealed that XAB06 significantly inhibited swarming motility, biofilm formation, and pyocyanin production, indicating interference with key virulence determinants of PA. Notably, XAB06 conferred protection in a murine model of sepsis using the reference strains PAO1, PA103, and a ST235 high-risk clone. Collectively, these findings demonstrate the broad PA coverage and the protective activity of XAB06, supporting its potential as a novel therapeutic strategy against PA.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0027726"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886074","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 of quabodepistat alone and in combination with delamanid and bedaquiline against <i>Mycobacterium tuberculosis</i> in an NHP model evaluated by [¹⁸F] FDG PET/CT and bacterial burden.","authors":"L E Via, J Sarathy, D M Weiner, T Greenstein, M Zimmerman, A Abdi, J D Fleegle, F Gomez, F Kaya, M K Piazza, A Vatthauer, B Y Sloan, K M Repoli, A M Walker, M J Woodcock, O Egbelowo, K Gausi, H I M Boshoff, Y Liu, D Chadalavada, B B Aldridge, V Dartois, C E Barry","doi":"10.1128/aac.00280-26","DOIUrl":"10.1128/aac.00280-26","url":null,"abstract":"<p><p>Multidrug-resistant tuberculosis (MDR-TB) is challenging. Bedaquiline (B), delamanid (D), and pretomanid (P) are used in combination regimens with other anti-TB drugs for MDR-TB; however, agents with novel mechanisms of action are needed. DprE1 inhibitor quabodepistat (Q) was developed for combination use. In this study, Q alone or in combination with human-equivalent doses of D and/or B was evaluated in a marmoset TB model using <i>in vivo</i> imaging, with terminal bacterial counts from all lung lesions. Marmosets were infected with H37Rv <i>Mycobacterium tuberculosis</i> and allowed to develop the disease for 7 weeks. They were then administered a pre-treatment ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and randomized into seven treatment groups (<i>n</i> = 5/group). At 2 weeks, the quabodepistat-treated groups showed a significant reduction in lesion volume compared to those without the agent in a post hoc analysis. After 2 months, the animals were euthanized, and the bacterial burden and histology were assessed. Marmosets treated with all agents showed reduced lung disease on PET/CT (>70%) compared to their pre-treatment disease volume. B reduced extrapulmonary bacteria more significantly than Q or D. Cavities and necrotic lesions from DBQ-treated animals had lower bacterial burdens than lesions treated with any of the single-agent or two-agent combinations. In a preliminary comparison, DBQ showed no statistically detectable difference from the standard-of-care regimen isoniazid-rifampicin-pyrazinamide-ethambutol (HRZE). Additionally, the activities of D and P monotherapies were similar in this model. The evaluation of these agents in the marmoset TB model supports further investigation of Q as a component of shorter TB regimens.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0028026"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975523","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 duty to act.","authors":"Emily Sickbert-Bennett, Philip J Rosenthal, Cesar A Arias, Gonzalo M Bearman, Paul E Sax, Graeme Forrest, David P Calfee, Romney M Humphries, Stanley Maloy, Ravi Jhaveri, Ira Blader, Ashley Shade, Roger Bedimo, Cynthia L Sears, Paul Katz, Barbara Resnick","doi":"10.1128/aac.01104-26","DOIUrl":"10.1128/aac.01104-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0110426"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A chloramine-based antiseptic polymer improves <i>Candida auris</i> skin decolonization compared to chlorhexidine in a murine model.","authors":"Janet Herrada, Lisa Long, Erin Marie San Valentin, Fnu Samiksha, Nicole Byrnes-Shaver, Lynne Harding, Thomas S McCormick, Mahmoud Ghannoum","doi":"10.1128/aac.00713-26","DOIUrl":"10.1128/aac.00713-26","url":null,"abstract":"<p><p><i>Candida auris</i> frequently demonstrates resistance to multiple antifungal classes and has been classified as a critical priority pathogen by the World Health Organization and the first fungal pathogen designated an urgent threat by the U.S. Centers for Disease Control and Prevention. Patients with skin colonization face a 7%-20% risk of invasive infection, with 30-day mortality of 30%-72%. While chlorhexidine gluconate (CHG) is widely used for general skin decolonization, it fails to reliably clear <i>C. auris</i> from patient skin, and no proven decolonization protocol exists. We evaluated a novel chloramine-based antiseptic polymer, polyvantoin chlorine (AVA-003). <i>In vitro</i> CLSI broth microdilution demonstrated activity against isolates from all four major <i>C. auris</i> clades (I-IV), with minimum inhibitory concentrations ranging from 250 to 500 µg/mL. Two proof-of-concept experiments using a validated murine model assessed <i>in vivo</i> efficacy. Female BALB/c mice were inoculated with clinical isolate <i>C. auris</i> MRL-35368 and treated with 1.2% AVA-003, 2% CHG, or vehicle controls across two phases examining formulation and treatment duration. AVA-003 reduced fungal burden at both ear and dorsal sites compared to untreated and CHG-treated controls. Specifically, 1.2% AVA-003 reduced ear burden versus untreated controls by 3.07 log colony-forming units (CFU)/g (<i>P</i> = 0.003, phase I) and versus 2% CHG at 3 days by 1.42 log CFU/g (<i>P</i> < 0.0001, phase II); dorsal burden was reduced by 3.58 log CFU/g versus untreated controls (<i>P</i> < 0.0001). In phase I, 1.2% AVA-003 achieved undetectable burden (0 CFU/g) at both sites. In phase II, AVA-003 significantly reduced but did not uniformly eradicate <i>C. auris</i> burden. Its advantage over CHG was greater at 3 days than 7 days, likely reflecting progressive dorsal hair regrowth, a recognized limitation of the murine model. These findings support AVA-003 as a promising <i>C. auris</i> decolonization candidate warranting further clinical investigation.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0071326"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787533","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":"Comparative effectiveness of ceftolozane/tazobactam relative to ceftazidime/avibactam for the treatment of adult, hospitalized patients with pneumonia due to multidrug-resistant <i>Pseudomonas aeruginosa</i> in U.S. Veterans Health Administration facilities.","authors":"Nicholas S Britt, Karim Khader, Tao He, Emily M Potter, Thomas P Lodise","doi":"10.1128/aac.00707-26","DOIUrl":"10.1128/aac.00707-26","url":null,"abstract":"<p><p>Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (C/A) are frequently used for the treatment of multidrug-resistant <i>Pseudomonas aeruginosa</i> (MDR-PSA) pneumonia. However, comparative \"real-world\" effectiveness data are limited. We performed a retrospective cohort study within the U.S. Veterans Health Administration (VHA; 2015-2019, 2022-2024), including adults with microbiologically confirmed MDR-PSA pneumonia receiving C/T or C/A within ≤5 days of index culture. Inverse probability of treatment weighting (IPTW) was applied to balance baseline covariates. The primary outcome was 30-day all-cause mortality, and secondary outcomes were 60-day mortality, 90-day mortality, and 30-, 60-, and 90-day MDR-PSA recurrence and all-cause hospital readmission. A prespecified sensitivity analysis examined the effect of early treatment initiation ≤72 h. Among 260 patients (C/T, <i>n</i> = 132; C/A, <i>n</i> = 128), C/T recipients demonstrated more extensive prior antimicrobial exposure and substantially longer time-to-therapy (median, 56 versus 19 h; <i>P</i> < 0.001). After IPTW, balance improved across most prespecified covariates, although residual imbalance persisted for age and geographic region. No statistically significant between-group differences were observed in 30-day mortality (adjusted risk ratio [aRR], 1.02; 95% confidence interval [CI], 0.56-1.83; <i>P</i> = 0.944) or in other clinical outcomes. Among patients with early treatment within 72 h (<i>n</i> = 175), no significant differences in 30-day mortality (aRR, 1.18; 95% CI, 0.47-2.93; <i>P</i> = 0.724) or other mortality, recurrence, or readmission outcomes were observed between C/T and C/A. In this national VHA cohort, C/T and C/A demonstrated comparable clinical, microbiologic, and healthcare utilization outcomes. These findings support consideration of either C/T or C/A for MDR-PSA pneumonia when used at appropriate doses.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0070726"},"PeriodicalIF":4.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910560","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}