Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with e coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance
- Creators
- 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.
- McNamara J.
- Sieler R.
- Garlick J.
- Costa J.
- Roney J.
- Pratt N.
- Tabaja H.
- Kmeid J.
- Tayyar R.
- El Zein S.
- Jones S.
- Cowan R.
- Tai A.
- Lin B.
- Rad B.
- MacMorran E.
- Pollard J.
- Dinleyici R.
- Istanbullu A.
- Ceylan B.
- Mert A.
- Hashhoush M.
- Dalwi T.
- Korman T.
- Azzam R.
- Birrell M.
- Hughes C.
- Khan S.
- Lau J.
- Lee L.
- Lim K.
- Lin Y. D.
- Lister D.
- New D.
- Rafiei N.
- Stewart J.
- Tai A.
- Trad M. A.
- Aye Yeung V.
- McBride S.
- Holland D.
- Hopkins C.
- Luey C.
- Taylor S.
- Morpeth S.
- Finney M.
- Martin M.
- Holland U.
- Ali J.
- Jureen R.
- Underwood N.
- Henderson A.
- Runnegar N.
- Slavin M.
- Robinson O.
- Rishu A.
- Shawkat S.
- Fish J.
- Chin Liew K.
- Newton P.
- Merelli M.
- Carnelutti A.
- Ussai S.
- Pecori D.
- Izharuddin E.
- Young B.
- Ding Y.
- Ram R.
- Kelly J.
- Joshi N.
- Richards G.
- Smith O.
- Alli A.
- Vermeulen I.
- Wright B.
- Grey C.
- Stewart A.
- Reddy D.
- Wasserman S.
- Richi H.
- Sultana K.
- Alanazi N.
- Bin Awad E.
- Franzetti F.
- Stolz A.
- De Kock E.
- Magongoa T.
- Dutoit M.
- Russo A.
- Dentone C.
- Eisen D.
- Heyer L.
- Others:
- 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.
- Mcnamara, J.
- Sieler, R.
- Garlick, J.
- Costa, J.
- Roney, J.
- Pratt, N.
- Tabaja, H.
- Kmeid, J.
- Tayyar, R.
- El Zein, S.
- Jones, S.
- Cowan, R.
- Tai, A.
- Lin, B.
- Rad, B.
- Macmorran, E.
- Pollard, J.
- Dinleyici, R.
- Istanbullu, A.
- Ceylan, B.
- Mert, A.
- Hashhoush, M.
- Dalwi, T.
- Korman, T.
- Azzam, R.
- Birrell, M.
- Hughes, C.
- Khan, S.
- Lau, J.
- Lee, L.
- Lim, K.
- Lin, Y. D.
- Lister, D.
- New, D.
- Rafiei, N.
- Stewart, J.
- Tai, A.
- Trad, M. A.
- Aye Yeung, V.
- Mcbride, S.
- Holland, D.
- Hopkins, C.
- Luey, C.
- Taylor, S.
- Morpeth, S.
- Finney, M.
- Martin, M.
- Holland, U.
- Ali, J.
- Jureen, R.
- Underwood, N.
- Henderson, A.
- Runnegar, N.
- Slavin, M.
- Robinson, O.
- Rishu, A.
- Shawkat, S.
- Fish, J.
- Chin Liew, K.
- Newton, P.
- Merelli, M.
- Carnelutti, A.
- Ussai, S.
- Pecori, D.
- Izharuddin, E.
- Young, B.
- Ding, Y.
- Ram, R.
- Kelly, J.
- Joshi, N.
- Richards, G.
- Smith, O.
- Alli, A.
- Vermeulen, I.
- Wright, B.
- Grey, C.
- Stewart, A.
- Reddy, D.
- Wasserman, S.
- Richi, H.
- Sultana, K.
- Alanazi, N.
- Bin Awad, E.
- Franzetti, F.
- Stolz, A.
- De Kock, E.
- Magongoa, T.
- Dutoit, M.
- Russo, A.
- Dentone, C.
- Eisen, D.
- Heyer, L.
Description
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.
Additional details
- URL
- http://hdl.handle.net/11567/993120
- URN
- urn:oai:iris.unige.it:11567/993120
- Origin repository
- UNIGE