Antoni Torres;南山 钟;Jan Pachl;Jean François Timsit;Marin Kollef;Zhangjing Chen;Jie Song;Dianna Taylor;Peter J. Laud;Gregory G. Stone;Joseph W. Chow
University of Barcelona;Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS);Centro de Investigación Biomédica en Red de Enfermedades Respiratorias;China Association for Science and Technology;Charles University;Centre National de Référence du Paludisme;Washington University School of Medicine in St. Louis;AstraZeneca;Taylormade Health;University of Sheffield;Pfizer Inc.
发表时间:2018-3
期 刊:The Lancet Infectious Diseases
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=85039424423&partnerID=8YFLogxK
Background: Nosocomial pneumonia is commonly associated with antimicrobial-resistant Gram-negative pathogens. We aimed to assess the efficacy and safety of ceftazidime-avibactam in patients with nosocomial pneumonia, including ventilator-associated pneumonia, compared with meropenem in a multinational, phase 3, double-blind, non-inferiority trial (REPROVE). Methods: Adults with nosocomial pneumonia (including ventilator-associated pneumonia), enrolled at 136 centres in 23 countries, were randomly assigned (1:1) to 2000 mg ceftazidime and 500 mg avibactam (by 2 h intravenous infusion every 8 h) or 1000 mg meropenem (by 30-min intravenous infusion every 8 h) for 7–14 days; regimens were adjusted for renal function. Computer-generated randomisation codes were stratified by infection type and geographical region with a block size of four. Participants and investigators were masked to treatment assignment. The primary endpoint was clinical cure at the test-of-cure visit (21–25 days after randomisation). Non-inferiority was concluded if the lower limit of the two-sided 95% CI for the treatment difference was greater than −12·5% in the coprimary clinically modified intention-to-treat and clinically evaluable populations. This trial is registered with ClinicalTrials.gov (NCT01808092) and EudraCT (2012-004006-96). Findings: Between April 13, 2013, and Dec 11, 2015, 879 patients were randomly assigned. 808 patients were included in the safety population, 726 were included in the clinically modified intention-to-treat population, and 527 were included in the clinically evaluable population. Predominant Gram-negative baseline pathogens in the microbiologically modified intention-to-treat population (n=355) were Klebsiella pneumoniae (37%) and Pseudomonas aeruginosa (30%); 28% were ceftazidime-non-susceptible. In the clinically modified intention-to-treat population, 245 (68·8%) of 356 patients in the ceftazidime-avibactam group were clinically cured, compared with 270 (73·0%) of 370 patients in the meropenem group (difference −4·2% [95% CI −10·8 to 2·5]). In the clinically evaluable population, 199 (77·4%) of 257 participants were clinically cured in the ceftazidime-avibactam group, compared with 211 (78·1%) of 270 in the meropenem group (difference −0·7% [95% CI −7·9 to 6·4]). Adverse events occurred in 302 (75%) of 405 patients in the ceftazidime-avibactam group versus 299 (74%) of 403 in the meropenem group (safety population), and were mostly mild or moderate in intensity and unrelated to study treatment. Serious adverse events occurred in 75 (19%) patients in the ceftazidime-avibactam group and 54 (13%) patients in the meropenem group. Four serious adverse events (all in the ceftazidime-avibactam group) were judged to be treatment related. Interpretation: Ceftazidime-avibactam was non-inferior to meropenem in the treatment of nosocomial pneumonia. These results support a role for ceftazidime-avibactam as a potential alternative to carbapenems in patients with nosocomial pneumonia (including ventilator-associated pneumonia) caused by Gram-negative pathogens. Funding: AstraZeneca.
医学与生命科学
Scopus度量
年份 | CiteScore | SJR | SNIP |
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1996 | |||
1997 | |||
1998 | |||
1999 | |||
2000 | |||
2001 | |||
2002 | 0.513 | 1.417 | |
2003 | 1.037 | 4.146 | |
2004 | 1.469 | 4.308 | |
2005 | 1.655 | 4.639 | |
2006 | 1.694 | 4.919 | |
2007 | 2.038 | 5.18 | |
2008 | 3.066 | 5.009 | |
2009 | 4.396 | 6.102 | |
2010 | 6.377 | 6.039 | |
2011 | 25 | 7.465 | 6.41 |
2012 | 29.7 | 9.044 | 6.584 |
2013 | 33.8 | 9.868 | 6.852 |
2014 | 33.7 | 12.609 | 7.669 |
2015 | 32.8 | 11.595 | 7.076 |
2016 | 32.9 | 11.218 | 6.688 |
2017 | 31.6 | 9.963 | 6.348 |
2018 | 31.9 | 9.462 | 6.29 |
2019 | 32.4 | 9.04 | 7.234 |
2020 | 30.1 |
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