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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

Authors :
Harris, P.N.A.
Tambyah, P.A.
Lye, D.C.
Mo, Y.
Lee, T.H.
Yilmaz, M.
Alenazi, T.H.
Arabi, Y.
Falcone, M.
Bassetti, M.
Righi, E.
Rogers, B.A.
Kanj, S.
Bhally, H.
Iredell, J.
Mendelson, M.
Boyles, T.H.
Looke, D.
Miyakis, S.
Walls, G.
Al Khamis, M.
Zikri, A.
Crowe, A.
Ingram, P.
Daneman, N.
Griffin, P.
Athan, E.
Lorenc, P.
Baker, P.
Roberts, L.
Beatson, S.A.
Peleg, A.Y.
Harris-Brown, T.
Paterson, D.L.
Robinson, J.O.
Harris, P.N.A.
Tambyah, P.A.
Lye, D.C.
Mo, Y.
Lee, T.H.
Yilmaz, M.
Alenazi, T.H.
Arabi, Y.
Falcone, M.
Bassetti, M.
Righi, E.
Rogers, B.A.
Kanj, S.
Bhally, H.
Iredell, J.
Mendelson, M.
Boyles, T.H.
Looke, D.
Miyakis, S.
Walls, G.
Al Khamis, M.
Zikri, A.
Crowe, A.
Ingram, P.
Daneman, N.
Griffin, P.
Athan, E.
Lorenc, P.
Baker, P.
Roberts, L.
Beatson, S.A.
Peleg, A.Y.
Harris-Brown, T.
Paterson, D.L.
Robinson, J.O.
Source :
Harris, P.N.A., Tambyah, P.A., Lye, D.C., Mo, Y., Lee, T.H., Yilmaz, M., Alenazi, T.H., Arabi, Y., Falcone, M., Bassetti, M., Righi, E., Rogers, B.A., Kanj, S., Bhally, H., Iredell, J., Mendelson, M., Boyles, T.H., Looke, D., Miyakis, S., Walls, G., Al Khamis, M., Zikri, A., Crowe, A., Ingram, P., Daneman, N., Griffin, P., Athan, E., Lorenc, P., Baker, P., Roberts, L., Beatson, S.A., Peleg, A.Y., Harris-Brown, T., Paterson, D.L. and Robinson, J.O. <
Publication Year :
2018

Abstract

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

Details

Database :
OAIster
Journal :
Harris, P.N.A., Tambyah, P.A., Lye, D.C., Mo, Y., Lee, T.H., Yilmaz, M., Alenazi, T.H., Arabi, Y., Falcone, M., Bassetti, M., Righi, E., Rogers, B.A., Kanj, S., Bhally, H., Iredell, J., Mendelson, M., Boyles, T.H., Looke, D., Miyakis, S., Walls, G., Al Khamis, M., Zikri, A., Crowe, A., Ingram, P., Daneman, N., Griffin, P., Athan, E., Lorenc, P., Baker, P., Roberts, L., Beatson, S.A., Peleg, A.Y., Harris-Brown, T., Paterson, D.L. and Robinson, J.O. <
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1276818766
Document Type :
Electronic Resource