{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:24:30Z","timestamp":1773019470391,"version":"3.50.1"},"reference-count":23,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2012,2,10]]},"published-print":{"date-parts":[[2012]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Secondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Nine mixed surgical\/medical intensive care units across Denmark.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>1200 adult intensive care patients, 18+\u2005years, expected to stay +24\u2005h. Exclusion criteria: bilirubin &gt;40\u2005mg\/dl, triglycerides &gt;1000\u2005mg\/dl, increased risk from blood sampling, pregnant\/breast feeding and psychiatric patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Patients were randomised to guideline-based therapy (\u2018standard-exposure\u2019 arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements (\u2018high-exposure\u2019 arm).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>\n                      Primary end point: estimated glomerular filtration rate (eGFR) &lt;60\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      . Secondary end points: (1) delta eGFR after starting\/stopping a drug and (2) RIFLE criterion\n                      <jats:italic>Risk<\/jats:italic>\n                      \u2018R\u2019,\n                      <jats:italic>Injury<\/jats:italic>\n                      \u2018I\u2019 and\n                      <jats:italic>Failure<\/jats:italic>\n                      \u2018F\u2019. Analysis was by intention to treat.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      28-day mortality was 31.8% and comparable (Jensen\n                      <jats:italic>et al<\/jats:italic>\n                      , Crit Care Med 2011). A total of 3672\/7634 (48.1%) study days during follow-up in the high-exposure versus 3016\/6949 (43.4%) in the \u2018standard-exposure arm were spent with eGFR &lt;60\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      , p&lt;0.001. In a multiple effects model, 3 piperacillin\/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h while exposed to this drug (95% CI 0.7 to 1.3\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h) vs meropenem: 2.9\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h (2.5 to 3.3\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h)); after discontinuing piperacillin\/tazobactam, the renal recovery rate increased: 2.7\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h (2.3 to 3.1\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      \/24\u2005h)). eGFR &lt;60\u2005ml\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Piperacillin\/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00271752\">NCT00271752<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2011-000635","type":"journal-article","created":{"date-parts":[[2012,3,12]],"date-time":"2012-03-12T20:30:34Z","timestamp":1331584234000},"page":"e000635","source":"Crossref","is-referenced-by-count":75,"title":["Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised 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