Antimicrobial Agents and Chemotherapy最新文献

{"title":"Emergence of a novel high-level tigecycline resistance gene <i>tet</i>(X6) variant coexisting with <i>tet</i>(X2) and two <i>tet</i>(X) copies in a <i>Sphingobacterium</i> sp.","authors":"Qiu Xu, Jie Hou, Stefan Schwarz, Jiyun Chai, Longhua Lin, Caiping Ma, Yao Zhu, Wanjiang Zhang","doi":"10.1128/aac.01758-24","DOIUrl":"10.1128/aac.01758-24","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0175824"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584462","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":"Fighting resistance with redundancy: a path forward for treating antimicrobial-resistant infections?","authors":"Jose M Munita, Pranita D Tamma","doi":"10.1128/aac.00121-25","DOIUrl":"10.1128/aac.00121-25","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) remains a major threat, with high mortality and limited effective treatments. Sulbactam-durlobactam has emerged as a promising therapy against CRAB. Sulbactam-durlobactam was combined with imipenem-cilastatin in a clinical trial that led to its United States Food and Drug Administration approval. However, the additive benefit of imipenem remains uncertain. In a recent study (Antimicrob Agents Chemother 69:e01627-24, 2025, https://doi.org/10.1128/aac.01627-24), Veeraraghavan and colleagues provide convincing mechanistic evidence that adding imipenem to sulbactam-durlobactam enhances bacterial killing, likely through complementary inhibition of penicillin binding proteins, leveraging the concept of target redundancy.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0012125"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623304","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":"Deletion of the <i>chloroquine resistance transporter</i> gene confers reduced piperaquine susceptibility to the rodent malaria parasite <i>Plasmodium berghei</i>.","authors":"Makoto Hirai, Meiji Arai, Soki Hayamichi, Ayako Uchida, Megumi Sudo, Rie Kubota, Naoaki Shinzawa, Toshihiro Mita","doi":"10.1128/aac.01589-24","DOIUrl":"10.1128/aac.01589-24","url":null,"abstract":"<p><p>Malaria parasites acquire drug resistance through genetic changes, the mechanisms of which remain incompletely understood. Understanding the mechanisms of drug resistance is crucial for the development of effective treatments against malaria, and for this purpose, new genetic tools are needed. In a previous study, as a forward genetic tool, we developed the rodent malaria parasite <i>Plasmodium berghei</i> mutator (PbMut) line, which has a greatly increased rate of mutation accumulation and from which we isolated a mutant with reduced susceptibility to piperaquine (PPQ). We identified a mutation in the <i>chloroquine resistance transporter</i> (PbCRT N331I) as responsible for this phenotype. In the current study, we generated a marker-free PbMut to enable further genetic manipulation of the isolated mutants. Here, we screened again for PPQ-resistant mutants in marker-free PbMut and obtained a parasite population with reduced susceptibility to PPQ. Of five isolated clones, none had the mutation PbCRT N331I; rather, they possessed a nonsense mutation at amino acid 119 (PbCRT Y119*), which would truncate the protein before eight of its ten predicted transmembrane domains. The PbCRT orthologue in the human malaria parasite <i>Plasmodium falciparum</i>, PfCRT, is an essential membrane transporter. To address the essentiality of PbCRT, we successfully deleted the full <i>PbCRT</i> gene [<i>PbCRT</i>(-)] from wild-type parasites. <i>PbCRT</i>(-) parasites exhibited reduced susceptibility to PPQ, along with compromised fitness in mice and following transmission to mosquitoes. Taken together, our findings provide the first evidence that <i>P. berghei</i> can acquire reduced PPQ susceptibility through complete loss of PbCRT function.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0158924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482054","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":"Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers.","authors":"James A Watson, Parinaz Mehdipour, Robert Moss, Podjanee Jittamala, Sophie Zaloumis, David J Price, Saber Dini, Borimas Hanboonkunupakarn, Pawanrat Leungsinsiri, Kittiyod Poovorawan, Kesinee Chotivanich, Germana Bancone, Robert J Commons, Nicholas P J Day, Sasithon Pukrittayakamee, Walter R J Taylor, Nicholas J White, Julie A Simpson","doi":"10.1128/aac.01549-24","DOIUrl":"10.1128/aac.01549-24","url":null,"abstract":"<p><p>Primaquine is the only widely available drug to prevent relapses of <i>Plasmodium vivax</i> malaria. Primaquine is underused because of concerns over oxidant hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency. A pharmacometric trial showed that ascending-dose radical cure primaquine regimens causing 'slow burn' hemolysis were safe in G6PD-deficient Thai and Burmese male volunteers. We developed and calibrated a within-host model of primaquine hemolysis in G6PD deficiency, using detailed serial hemoglobin and reticulocyte count data from 23 hemizygote deficient volunteers given ascending-dose primaquine (1,523 individual measurements over 656 unique time points). We estimate that primaquine doses of ~0.75 mg base/kg reduce the circulating lifespan of deficient erythrocytes by ~30 days in individuals with common Southeast Asian <i>G6PD</i> variants. We predict that 5 mg/kg primaquine total dose can be administered safely to G6PD-deficient individuals over 14 days with expected hemoglobin drops of 18 to 43% (2.7 to 6.5 g/dL drop from a baseline of 15 g/dL).CLINICAL TRIALSThis study is registered with the Thai Clinical Trials Registry (TCTR) as TCTR20170830002 and TCTR20220317004.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0154924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482139","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":"Antimicrobial susceptibility of <i>Stenotrophomonas maltophilia</i> from United States medical centers (2019-2023).","authors":"Helio S Sader, Mariana Castanheira, S J Ryan Arends, Timothy B Doyle","doi":"10.1128/aac.00124-25","DOIUrl":"10.1128/aac.00124-25","url":null,"abstract":"<p><p>We evaluated the antimicrobial susceptibility of 1,400 clinical isolates of <i>Stenotrophomonas maltophilia</i> consecutively collected from United States medical centers in 2019-2023. Aztreonam-avibactam (MIC_50/90, 2/4 µg/mL; 99.6% inhibited at ≤8 µg/mL) was the most active compound, followed by trimethoprim-sulfamethoxazole (MIC_50/90, ≤0.12/0.5 µg/mL; 96.9% susceptible), minocycline (MIC_50/90, 0.5/2 µg/mL; 89.2% susceptible), and levofloxacin (MIC_50/90, 1/8 µg/mL; 78.9% susceptible). Aztreonam-avibactam retained potent activity against isolates not susceptible to trimethoprim-sulfamethoxazole, minocycline, and/or levofloxacin (99.3%-100.0% inhibited at ≤8 µg/mL).</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0012425"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565862","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":"Deciphering meropenem persistence in <i>Acinetobacter baumannii</i> facilitates discovery of anti-persister activity of thymol.","authors":"Arsalan Hussain, Timsy Bhando, Ananth Casius, Rinki Gupta, Ranjana Pathania","doi":"10.1128/aac.01381-24","DOIUrl":"10.1128/aac.01381-24","url":null,"abstract":"<p><p>Decades of antibiotic misuse have accelerated the emergence of multi- and extensively drug-resistant bacteria. Bacterial pathogens employ several strategies such as antibiotic resistance, tolerance, and biofilm formation in response to extreme environments and antibiotic stress. Another crucial survival mechanism involves the stochastic generation of bacterial subpopulations known as persisters, which can endure high concentrations of antibiotics. Upon removal of antibiotic stress, these subpopulations revert back to their original phenotype which links them to the relapse and recalcitrance of chronic infections, a significant problem in clinical settings. Persistent infections are particularly notable in <i>Acinetobacter baumannii</i>, a top-priority ESKAPE pathogen, where carbapenems serve as last-resort antibiotics. Several reports indicate the rising therapeutic failure of carbapenems due to persistence, underscoring the importance of developing anti-persister therapeutics. In this study, we explored the mechanisms of transient persister formation in <i>A. baumannii</i> against meropenem. Our investigation revealed significant changes in membrane properties and energetics in meropenem persisters of <i>A. baumannii</i>, including a noteworthy increase in tolerance to other antibiotics. This understanding guided the evaluation of an in-house collection of GRAS status compounds for their potential anti-persister activity. The compound thymol demonstrated remarkable inhibitory activity against meropenem persisters of <i>A. baumannii</i> and other ESKAPE pathogens. Further investigation revealed its impact on persister cell physiology, including efflux pump inhibition and disruption of cellular respiration. Given our results, we propose a compelling strategy where thymol could be employed either as a monotherapy or in combination with meropenem in anti-persister therapeutics.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0138124"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456844","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":"The microbiome-restorative potential of ibezapolstat for the treatment of <i>Clostridioides difficile</i> infection is predicted through variant PolC-type DNA polymerase III in Lachnospiraceae and Oscillospiraceae.","authors":"Jacob K McPherson, Julian G Hurdle, Matthew L Baker, Tahir Hussain, Ashok Kumar, Kevin W Garey","doi":"10.1128/aac.01679-24","DOIUrl":"10.1128/aac.01679-24","url":null,"abstract":"<p><p>Ibezapolstat (IBZ), a first-in-class antibiotic targeting the PolC-type DNA polymerase III alpha-subunit (PolC) in low G + C bacteria, is in clinical development for the treatment of <i>Clostridioides difficile</i> infection (CDI). In the phase 2 trials, IBZ had potent activity against <i>C. difficile</i> while sparing or causing regrowth of Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales, common commensal low G + C bacteria. The purpose of this study was to utilize <i>in silico</i> approaches to better interpret the narrower than expected IBZ spectrum of activity. IBZ susceptibility to human commensal microbiota was predicted using genomic analysis and PolC phylogenetic tree construction in relation to <i>C. difficile</i> and commensal low G + C bacteria. Protein structure prediction was performed using AlphaFold2 and binding pocket homology modeling was performed using Schrodinger Maestro and UCSF ChimeraX. An amino acid phylogenetic tree identified certain residues that were phylogenetically variant in Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales and conserved in <i>C. difficile</i>. Chemical modeling showed that these residues ablated key PolC•IBZ predicted interactions including two lysine \"<i>gates</i>\" (_CdiPolCLys1148 and _CdiPolCLys1327) that \"<i>latch</i>\" onto the compound; an \"<i>anchoring</i>\" interaction (_CdiPolCThr1331) to the central moiety; and a stabilized set of <i>C. difficile</i> sensitizer residues (_CdiPolCThr1291 and _CdiPolCLys1292) that resulted in the prolonged inhibition of a catalytic residue (_CdiPolCAsp1090). The observed IBZ sparing of Lachnospiraceae, Oscillospiraceae, and Erysipelotrichaceae/Coprobacillaceae was predicted using <i>in silico</i> techniques. Further studies that confirm a PolC structural basis for the IBZ narrower than expected activity are needed to confirm these <i>in silico</i> phylogenetic and chemical modeling data.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0167924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466718","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":"Population pharmacokinetics and clinical assessment of linezolid in pediatric bacterial infections.","authors":"Xue Tian, Tingting Jiang, Lei Dong, Xinfang Zhang, Weiwei Jiao, Gang Liu, Qinjing Li, Jing Bi, Dianping You, Ling Cao, Wenhui Guo, Zhipeng Jin, Qunqun Zhang, Yongsheng Xu, Wei Zhao, Hui Qi, Yi Zheng, Adong Shen","doi":"10.1128/aac.01299-24","DOIUrl":"https://doi.org/10.1128/aac.01299-24","url":null,"abstract":"<p><p>The pharmacokinetic profile of linezolid still needs further definition, and insufficient or excessive exposure may lead to treatment failure or development of adverse events. Our study aimed to establish a population pharmacokinetic (PPK) model for linezolid in children with bacterial infections, develop an optimal dosage, and evaluate its efficacy and safety. A total of 157 plasma samples from 80 patients were utilized in PPK modeling. A one-compartment model with first-order elimination was most suitable for describing the PK characteristics of linezolid. Weight and creatinine clearance were the significant covariates for clearance. The outcomes of Monte Carlo revealed that in children under 12 years, the probability of target attainment (PTA) for standard dosage (10 mg/kg q8h) was over 90.0% when minimum inhibitory concentration (MIC) ≤2 µg/mL, with a mere 1.4% probability of surpassing the safety threshold. Meanwhile, in children aged 12 years and above, the PTA for standard dosage (600 mg q12h) was over 83.0%, and the probability of surpassing the safety threshold was 0.0%. To take the results one step further, a total of 67 patients (using standard dosage) were enrolled in the efficacy and safety analysis. Of the patients, 95.5% were cured or improved clinical treatment outcomes, and 22.4% of the patients developed possible adverse events (AEs), and no patient experienced early discontinuation of linezolid due to AEs. The standard dosage of linezolid is effective and safe in children with bacterial infections (MIC ≤2 µg/mL). For pathogens with MIC >2 µg/mL, it is advisable to switch antibiotics or increase dosage.CLINICAL TRIALSThis study is registered with Chinese Clinical Trial Registry as ChiCTR 2200061207<b>.</b></p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0129924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750844","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 effect of pregnancy on the population pharmacokinetics of levofloxacin in South Africans with rifampicin-resistant tuberculosis.","authors":"Sharon Sawe, Lufina Tsirizani, Richard Court, Kamunkhwala Gausi, Asanda Poswa, Tasnim Badat, Lubbe Wiesner, Marian Loveday, Gary Maartens, Francesca Conradie, Paolo Denti","doi":"10.1128/aac.01626-24","DOIUrl":"10.1128/aac.01626-24","url":null,"abstract":"<p><p>Levofloxacin is a key drug in the prevention and treatment of rifampicin-resistant tuberculosis (RR-TB). There are limited data describing the effect of pregnancy on the pharmacokinetics of levofloxacin. We aimed to characterize the pharmacokinetics of levofloxacin in adults with RR-TB, including the effect of pregnancy. We pooled data from two studies conducted in adult participants treated for RR-TB in South Africa. Treatment regimens in both studies included levofloxacin dosed at 750/1000 mg daily, depending on body weight. We analyzed data from 47 participants, 31 (66%) living with HIV, using nonlinear mixed-effects modeling in NONMEM v7.5.1. Out of 33 female participants, 21 were pregnant, of whom 12 contributed matched antepartum and postpartum pharmacokinetic profiles. Levofloxacin followed one-compartment pharmacokinetics with first-order elimination and absorption with transit absorption compartments. The clearance and volume of distribution for a typical non-pregnant participant (weight: 58 kg; age: 32 years; serum creatinine: 56.2 µmol/L) were 6.06 (95% confidence interval [CI], 5.47 to 6.53) L/h and 85.9 (95% CI, 80.6 to 91.7) L, respectively. Higher serum creatinine levels were associated with lower levofloxacin clearance using a power function with an exponent of -0.367 (95% CI, -0.493 to -0.104). Pregnancy increased levofloxacin clearance by 38.1% (95% CI, 23.4% to 57.1%), with substantially lower exposures in pregnant compared with non-pregnant participants receiving equivalent weight-based doses. To achieve non-pregnant equivalent exposures of levofloxacin, an additional 250 mg tablet may be required, although further study is needed to assess the safety implications of a higher recommended dose in pregnant women.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0162624"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750848","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":"Spectrum of cefepime-taniborbactam coverage against 190 β-lactamases defined in engineered isogenic <i>Escherichia coli</i> strains.","authors":"Tsuyoshi Uehara, Cassandra L Chatwin, Brittany Miller, Mitchell Edwards, Annie Stevenson, Jenna Colombo, David A Six, Denis M Daigle, Greg Moeck, Steven A Boyd, Daniel C Pevear","doi":"10.1128/aac.01699-24","DOIUrl":"https://doi.org/10.1128/aac.01699-24","url":null,"abstract":"<p><p>Cefepime-taniborbactam is a β-lactam/β-lactamase inhibitor combination in clinical development for the treatment of Enterobacterales and <i>Pseudomonas</i> infections, including carbapenem-resistant Enterobacterales and multidrug-resistant <i>Pseudomonas aeruginosa</i>. Taniborbactam is a novel cyclic boronate with direct inhibitory activity against clinically relevant Ambler class A, B, C, and D β-lactamases. To further characterize the spectrum of β-lactamase coverage by cefepime-taniborbactam, we constructed 190 isogenic strains of <i>Escherichia coli</i> that constitutively expressed a different β-lactamase. Synthetic codon-optimized genes encoding the mature periplasmic protein linked to the TEM-1 signal sequence were used for optimized expression and periplasmic localization of the β-lactamase. The repertoire of β-lactamases consisted of 50 Ambler class A, 34 class B (metallo), 48 class C, and 58 class D enzymes known to mediate β-lactam resistance in the clinical isolates of Enterobacterales and <i>P. aeruginosa</i>. Overall, in the 190 isogenic strains, the MIC₅₀/MIC₉₀ values were 8/128 µg/mL for cefepime and >128/>128 µg/mL for ceftazidime. Cefepime-taniborbactam (MIC₅₀/MIC₉₀ of 0.25/8 µg/mL) showed greater activity than ceftazidime-avibactam (MIC₅₀/MIC₉₀ of 4/>128 µg/mL) and similar activity to aztreonam-avibactam (MIC₅₀/MIC₉₀ of 0.5/4 µg/mL). Cefepime-taniborbactam inhibited strains overproducing metallo-β-lactamases, including clinically important NDM and VIM enzymes, whereas ceftazidime-avibactam showed no coverage. Among the 129 β-lactamase-overproducing strains with increased cefepime MIC ≥16-fold relative to the control strain, taniborbactam potentiated cefepime MIC by ≥8-fold for 113 strains overexpressing β-lactamases (42 Ambler class A, 24 B, 23 C, and 24 D). Cefepime-taniborbactam demonstrated broader activity relative to ceftazidime-avibactam and comparable activity with aztreonam-avibactam in the overall coverage of both serine- and metallo-β-lactamases from all four Ambler classes.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0169924"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750846","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}