ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate β-lactamase inhibitor taniborbactam combined with cefepime.

التفاصيل البيبلوغرافية
العنوان:	ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate β-lactamase inhibitor taniborbactam combined with cefepime.
المؤلفون:	Jacobs MR; Case Western Reserve University, Cleveland, Ohio, USA.; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Abdelhamed AM; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Good CE; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Mack AR; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA., Bethel CR; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA., Marshall S; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA., Hujer AM; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Hujer KM; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Patel R; Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., van Duin D; Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA., Fowler VG; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA., Rhoads DD; Case Western Reserve University, Cleveland, Ohio, USA.; Department of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA., Six DA; Venatorx Pharmaceuticals Inc., Malvern, Pennsylvania, USA., Moeck G; Venatorx Pharmaceuticals Inc., Malvern, Pennsylvania, USA., Uehara T; Venatorx Pharmaceuticals Inc., Malvern, Pennsylvania, USA., Papp-Wallace KM; Case Western Reserve University, Cleveland, Ohio, USA.; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA., Bonomo RA; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Research Service, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Departments of Biochemistry, Pharmacology, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA.
المصدر:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Sep 04; Vol. 68 (9), pp. e0075124. Date of Electronic Publication: 2024 Aug 12.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, American Society for Microbiology
مواضيع طبية MeSH:	Cefepime/pharmacology , Pseudomonas aeruginosa/drug effects , Microbial Sensitivity Tests* , Klebsiella pneumoniae/drug effects , Anti-Bacterial Agents/pharmacology , beta-Lactamase Inhibitors/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects, Cephalosporins/pharmacology ; Humans ; beta-Lactamases/metabolism ; beta-Lactamases/genetics ; Boronic Acids/pharmacology ; Carbapenems/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Ceftazidime/pharmacology ; Borinic Acids/pharmacology ; Drug Combinations ; Azabicyclo Compounds/pharmacology ; Carboxylic Acids
مستخلص:	Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC 90 values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa , MIC 90 values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa . Competing Interests: Robert A. Bonomo reports grants from Venatorx, Entasis, Merck, Wockhardt, and Shionogi outside the submitted work. David A. Six, Greg Moeck, and Tsuyoshi Uehara are employees of Venatorx Pharmaceuticals, Inc.
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معلومات مُعتمدة:	R21 AI114508 United States AI NIAID NIH HHS; UM1 AI104681 United States AI NIAID NIH HHS; 1I01BX002872 U.S. Department of Veterans Affairs (VA); 1I01BX001974 U.S. Department of Veterans Affairs (VA); UM1AI104681 HHS \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); I01 BX002872 United States BX BLRD VA; I01 BX001974 United States BX BLRD VA; R21AI114508 HHS \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID)
فهرسة مساهمة:	Keywords: Klebsiella pneumoniae; Pseudomonas aeruginosa; beta-lactamase inhibitor; bicyclic boronate; cefepime taniborbactam; taniborbactam
المشرفين على المادة:	807PW4VQE3 (Cefepime) 0 (Anti-Bacterial Agents) 8IGQ156Z07 (taniborbactam) 0 (beta-Lactamase Inhibitors) 0 (Cephalosporins) EC 3.5.2.6 (beta-Lactamases) 0 (Boronic Acids) 0 (Carbapenems) 0 (Bacterial Proteins) 9M416Z9QNR (Ceftazidime) 0 (Borinic Acids) 0 (Drug Combinations) 0 (Azabicyclo Compounds) 0 (avibactam, ceftazidime drug combination) 0 (Carboxylic Acids)
تواريخ الأحداث:	Date Created: 20240812 Date Completed: 20240904 Latest Revision: 20240906
رمز التحديث:	20240906
مُعرف محوري في PubMed:	PMC11373228
DOI:	10.1128/aac.00751-24
PMID:	39133021
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1098-6596
DOI:	10.1128/aac.00751-24