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Tytuł:
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Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial.
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Autorzy:
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Harris PNA; University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.; Department of Microbiology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.; Infection Management Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Tambyah PA; Department of Infectious Diseases, National University Hospital, Singapore.
Lye DC; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Mo Y; Department of Infectious Diseases, National University Hospital, Singapore.
Lee TH; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Yilmaz M; Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey.
Alenazi TH; King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Arabi Y; King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Falcone M; Department of Public Health and Infectious Diseases, 'Sapienza' University of Rome, Italy.
Bassetti M; Infectious Diseases Clinic, Department of Medicine University of Udine and Santa Maria Misericordia Hospital, Udine, Italy.
Righi E; Infectious Diseases Clinic, Department of Medicine University of Udine and Santa Maria Misericordia Hospital, Udine, Italy.
Rogers BA; Monash University, Centre for Inflammatory Diseases, Melbourne, Victoria, Australia.; Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia.
Kanj S; Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Bhally H; Department of Medicine and Infectious Diseases, North Shore Hospital, Auckland, New Zealand.
Iredell J; Marie Bashir Institute for Infectious Disease and Biosecurity, University of Sydney, Sydney, New South Wales, Australia.; Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia.
Mendelson M; Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
Boyles TH; Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
Looke D; Infection Management Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.; University of Queensland, Brisbane, Queensland, Australia.
Miyakis S; School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.; Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.; Department of Infectious Diseases, Wollongong Hospital, Wollongong, New South Wales, Australia.
Walls G; Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand.
Al Khamis M; King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Zikri A; King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Crowe A; Department of Infectious Diseases, St Vincent's Hospital, Melbourne, Victoria, Australia.; Department of Microbiology, St Vincent's Hospital, Melbourne, Victoria, Australia.
Ingram P; School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia.; Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Australia.; Department of Microbiology, PathWest Laboratory Medicine, Perth, Western Australia.
Daneman N; Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Griffin P; University of Queensland, Brisbane, Queensland, Australia.; Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Queensland, Australia.; QIMR Berghofer, Brisbane, Queensland, Australia.
Athan E; Department of Infectious Diseases, Barwon Health and Deakin University, Geelong, Victoria, Australia.
Lorenc P; University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
Baker P; School of Public Health, University of Queensland, Brisbane, Queensland, Australia.
Roberts L; Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, Australia.
Beatson SA; Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, Australia.
Peleg AY; Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.; Department of Microbiology, Monash University, Clayton, Australia.; Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Harris-Brown T; University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.
Paterson DL; University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.; Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
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Corporate Authors:
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MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)
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Źródło:
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JAMA [JAMA] 2018 Sep 11; Vol. 320 (10), pp. 984-994.
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Typ publikacji:
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Comparative Study; Equivalence Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Chicago : American Medical Association, 1960-
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MeSH Terms:
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Klebsiella pneumoniae*/drug effects
Anti-Bacterial Agents/*therapeutic use
Bacteremia/*mortality
Escherichia coli Infections/*drug therapy
Klebsiella Infections/*drug therapy
Penicillanic Acid/*analogs & derivatives
Thienamycins/*therapeutic use
Adult ; Aged ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/pharmacology ; Bacteremia/drug therapy ; Cause of Death ; Ceftriaxone/pharmacology ; Drug Resistance, Bacterial ; Escherichia coli/drug effects ; Escherichia coli Infections/mortality ; Female ; Humans ; Klebsiella Infections/mortality ; Male ; Meropenem ; Middle Aged ; Penicillanic Acid/adverse effects ; Penicillanic Acid/therapeutic use ; Piperacillin/adverse effects ; Piperacillin/therapeutic use ; Piperacillin, Tazobactam Drug Combination ; Thienamycins/adverse effects
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References:
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Contributed Indexing:
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Investigator: J McNamara; R Sieler; J Garlick; J Costa; J Roney; N Pratt; H Tabaja; J Kmeid; R Tayyar; S El Zein; S Jones; R Cowan; A Tai; B Lin; B Rad; E MacMorran; J Pollard; R Dinleyici; A Istanbullu; B Ceylan; A Mert; M Hashhoush; T Dalwi; T Korman; R Azzam; M Birrell; C Hughes; S Khan; J Lau; L Lee; K Lim; YD Lin; D Lister; D New; N Rafiei; J Stewart; A Tai; MA Trad; V Aye Yeung; S McBride; D Holland; C Hopkins; C Luey; S Taylor; S Morpeth; M Finney; M Martin; U Holland; J Ali; R Jureen; N Underwood; A Henderson; N Runnegar; M Slavin; O Robinson; A Rishu; S Shawkat; J Fish; K Chin Liew; P Newton; M Merelli; A Carnelutti; S Ussai; D Pecori; E Izharuddin; B Young; Y Ding; R Ram; J Kelly; N Joshi; G Richards; O Smith; A Alli; I Vermeulen; B Wright; C Grey; A Stewart; D Reddy; S Wasserman; H Richi; K Sultana; N Alanazi; E Bin Awad; F Franzetti; A Stolz; E De Kock; T Magongoa; M Dutoit; A Russo; C Dentone; D Eisen; L Heyer
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Molecular Sequence:
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ANZCTR ACTRN12613000532707; ACTRN12615000403538
ClinicalTrials.gov NCT02176122
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Substance Nomenclature:
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0 (Anti-Bacterial Agents)
0 (Thienamycins)
157044-21-8 (Piperacillin, Tazobactam Drug Combination)
75J73V1629 (Ceftriaxone)
87-53-6 (Penicillanic Acid)
FV9J3JU8B1 (Meropenem)
X00B0D5O0E (Piperacillin)
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Entry Date(s):
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Date Created: 20180913 Date Completed: 20180926 Latest Revision: 20220408
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Update Code:
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20240104
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PubMed Central ID:
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PMC6143100
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DOI:
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10.1001/jama.2018.12163
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PMID:
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30208454
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Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.
Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.
Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.
Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.
Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.
Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.
Conclusions and Relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.
Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.
Comment in: JAMA. 2018 Sep 11;320(10):979-981. (PMID: 30208439)
Comment in: JAMA. 2019 Feb 12;321(6):612-613. (PMID: 30747960)
Comment in: JAMA. 2019 Feb 12;321(6):613. (PMID: 30747961)
Erratum in: JAMA. 2019 Jun 18;321(23):2370. (PMID: 31211326)
