Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial

TY - JOUR

T1 - Kidney failure related to broad-spectrum antibiotics in critically ill patients

T2 - secondary end point results from a 1200 patient randomised trial

AU - Jensen, Jens-Ulrik Stæhr

AU - Hein, Lars

AU - Lundgren, Bettina

AU - Bestle, Morten Heiberg

AU - Mohr, Thomas

AU - Andersen, Mads Holmen

AU - Thornberg, Klaus Julius

AU - Løken, Jesper

AU - Steensen, Morten

AU - Fox, Zoë

AU - Tousi, Hamid

AU - Søe-Jensen, Peter

AU - Lauritsen, Anne Øberg

AU - Strange, Ditte Gry

AU - Reiter, Nanna

AU - Thormar, Katrin

AU - Fjeldborg, Paul Christian

AU - Larsen, Kim Michael

AU - Drenck, Niels-Erik

AU - Johansen, Maria Egede

AU - Nielsen, Lene Ryom

AU - Ostergaard, Christian

AU - Kjær, Jesper

AU - Grarup, Jesper

AU - Lundgren, Jens D

AU - Procalcitonin And Survival Study (PASS) Group

PY - 2012

Y1 - 2012

N2 - Objectives: To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients. Design: 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. Setting: Nine mixed surgical/medical intensive care units across Denmark. Participants: 1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients. Interventions: Patients were randomised to guidelinebased therapy ('standard-exposure' arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements ('high-exposure' arm). Main outcome measures: Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk 'R', Injury 'I' and Failure 'F'. Analysis was by intention to treat. Results: 28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the highexposure versus 3016/6949 (43.4%) in the 'standardexposure arm were spent with eGFR <60 ml/min/1.73 m 2, p<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 ml/min/1.73 m 2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m 2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m 2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m 2/24 h (2.3 to 3.1 ml/min/1.73 m 2/24 h)). eGFR <60 ml/min/1.73 m 2 in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively. Conclusions: 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.

AB - Objectives: To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients. Design: 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. Setting: Nine mixed surgical/medical intensive care units across Denmark. Participants: 1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients. Interventions: Patients were randomised to guidelinebased therapy ('standard-exposure' arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements ('high-exposure' arm). Main outcome measures: Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk 'R', Injury 'I' and Failure 'F'. Analysis was by intention to treat. Results: 28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the highexposure versus 3016/6949 (43.4%) in the 'standardexposure arm were spent with eGFR <60 ml/min/1.73 m 2, p<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 ml/min/1.73 m 2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m 2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m 2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m 2/24 h (2.3 to 3.1 ml/min/1.73 m 2/24 h)). eGFR <60 ml/min/1.73 m 2 in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively. Conclusions: 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.

U2 - 10.1136/bmjopen-2011-000635

DO - 10.1136/bmjopen-2011-000635

M3 - Journal article

C2 - 22411933

SN - 2044-6055

VL - 2

SP - e000635

JO - BMJ Open

JF - BMJ Open

IS - 2

ER -