{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:36:51Z","timestamp":1791387411947,"version":"4.3.3"},"reference-count":45,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001704","name":"European Society of Clinical Microbiology and Infectious Diseases","doi-asserted-by":"publisher","award":["Research Grant programme 2020"],"award-info":[{"award-number":["Research Grant programme 2020"]}],"id":[{"id":"10.13039\/501100001704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,11,19]]},"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The optimal treatment for extended-spectrum \u03b2-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections has yet to be defined. Retrospective studies have shown conflicting results, with most data suggesting the non-inferiority of beta-lactam\u2013beta-lactamase inhibitor combinations compared with carbapenems. However, the recently published MERINO trial failed to demonstrate the non-inferiority of piperacillin\u2013tazobactam to meropenem. The potential implications of the MERINO trial are profound, as widespread adoption of carbapenem treatment will have detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria. Therefore, we believe that it is justified to re-examine the comparison in a second randomised controlled trial prior to changing clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      PeterPen is a multicentre, investigator-initiated, open-label, randomised controlled non-inferiority trial, comparing piperacillin\u2013tazobactam with meropenem for third-generation cephalosporin-resistant\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      and\n                      <jats:italic>Klebsiella<\/jats:italic>\n                      bloodstream infections. The study is currently being conducted in six centres in Israel and one in Canada with other centres from Israel, Italy and Canada expected to join. The two primary outcomes are all-cause mortality at day 30 from enrolment and treatment failure at day seven (death, fever above 38\u00b0C in the last 48 hours, continuous symptoms, increasing Sequential Organ Failure Assessment Score or persistent blood cultures with the index pathogen). A sample size of 1084 patients was calculated for the mortality endpoint assuming a 12.5% mortality rate in the control group with a 5% non-inferiority margin and assuming 100% follow-up for this outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration numbers<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Registry (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03671967\">NCT03671967<\/jats:ext-link>\n                      ); Israeli Ministry of Health Trials Registry (MOH_2018-12-25_004857).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-040210","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T17:27:14Z","timestamp":1612805234000},"page":"e040210","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Piperacillin\u2013tazobactam versus meropenem for treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacteriaceae: a study protocol for a non-inferiority open-label randomised controlled trial (PeterPen)"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct03671967","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7495-3398","authenticated-orcid":false,"given":"Roni","family":"Bitterman","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel"},{"name":"Technion Israel Institute of Technology Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidi","family":"Koppel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Rambam Health Care Campus, Haifa, 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