Article Text
PDF
Abstract
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 guideline-based 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 m2. 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 high-exposure versus 3016/6949 (43.4%) in the ‘standard-exposure arm were spent with eGFR <60 ml/min/1.73 m2, 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 m2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m2/24 h (2.3 to 3.1 ml/min/1.73 m2 /24 h)). eGFR <60 ml/min/1.73 m2 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.
Trial registration ClinicalTrials.gov identifier: NCT00271752.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
Statistics from Altmetric.com
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Files in this Data Supplement:
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
- Data Supplement - Manuscript file of format pdf
Footnotes
↵* Participating investigators are listed in the appendix 1.
To cite: Jensen J-US, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open 2012;2:e000635. doi:10.1136/bmjopen-2011-000635
Contributors J-USJ designed the study, made the data collection tools, monitored data collection for the whole trial, wrote the statistical analysis plan and drafted the paper. He is guarantor. J-USJ, ZF and JK cleaned and analysed the data. JL, BL, LH, MHB, TM, MHA, KJT, JL, MS, HT, PS-J, AØL, DGS, NR, KT, PCF, KML, N-ED, MEJ, LRN, CØ, ZF, JK and JG made input study design, data collection tools and analysis plan on the manuscript. J-USJ implemented the trial at the centres. All members of the Procalcitonin And Survival Study Group assisted in designing the trial.
Funding This study was supported by grants from the Danish Research Council, The Lundbeck Foundation, Research Foundation for the Capitol Region of Denmark, The Toyota Foundation, Brahms Diagnostica (un-restricted grant), The Harboe Foundation, The A.P. Møller Foundation and the Idella Foundation. None of these had any influence on the design or conduct of the study; collection, management, analysis and interpretation of the data or the preparation or approval of the manuscript. All authors had full access to all the data in the study and conjointly take responsibility for the integrity of the data and the accuracy of the data analysis.
Competing interests All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that the trial was funded mainly by the Danish State (Danish Research Council), and all authors state that they have no relationships with companies that might have an interest in the submitted work in the previous 3 years; their spouses, partners or children have no financial relationships that may be relevant to the submitted work, and all authors have no non-financial interests that may be relevant to the submitted work.
Patient consent We received written consent from the patient or the next of kin for trial inclusion.
Ethics approval Ethical approval was provided by the ethics committee for Copenhagen and Frederiksberg Community (now Ethics Committee for the Capitol Region): H-KF-01-272-753.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data available.