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Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial
- 作者:Patrick NA Harris (1)
Anton Y Peleg (2) Jon Iredell (3) Paul R Ingram (4) (5) Spiros Miyakis (6) Andrew J Stewardson (7) Benjamin A Rogers (8) Emma S McBryde (9) Jason A Roberts (10) Jeff Lipman (10) Eugene Athan (11) Sanjoy K Paul (12) Peter Baker (13) Tiffany Harris-Brown (1) David L Paterson (1)
1. University of Queensland Centre for Clinical Research ; Building 71/918 Royal Brisbane & Women鈥檚 Hospital Campus ; Herston ; 4029 ; Brisbane ; QLD ; Australia 2. Department of Infectious Diseases ; The Alfred Hospital ; Melbourne ; VIC ; Australia 3. Westmead Millenium Institute for Medical Research ; Westmead Hospital ; Sydney ; NSW ; Australia 4. Department of Microbiology and Infectious Diseases ; Royal Perth Hospital ; Perth ; WA ; Australia 5. School of Pathology and Laboratory Medicine ; University of Western Australia ; Crawley ; WA ; Australia 6. Department of Infectious Diseases ; School of Medicine ; University of Wollongong and The Wollongong Hospital ; Wollongong ; NSW ; Australia 7. Department of Infectious Diseases ; Austin Health ; Melbourne ; VIC ; Australia 8. Monash Infectious Disease ; Monash Health ; Clayton ; VIC ; Australia 9. Victorian Infectious Diseases Unit ; Royal Melbourne Hospital ; Melbourne ; VIC ; Australia 10. Burns Trauma and Critical Care Research Centre ; The University of Queensland ; Brisbane ; QLD ; Australia 11. Department of Infectious Disease ; Barwon Health ; Deakin University ; Geelong ; VIC ; Australia 12. Clinical Trials & Biostatistics Unit ; QIMR Berghofer Medical Research Institute ; Brisbane ; QLD ; Australia 13. Queensland Clinical Trials and Biostatistics Centre ; University of Queensland ; Brisbane ; QLD ; Australia
- 关键词:Extended ; spectrum beta ; lactamase ; ESBL ; Plasmid ; AmpC ; Therapy ; Resistance ; Beta ; lactam/beta ; lactamase inhibitor ; Carbapenem ; Clinical trial
- 刊名:Trials
- 出版年:2015
- 出版时间:December 2015
- 年:2015
- 卷:16
- 期:1
- 全文大小:600 KB
- 参考文献:1. Cohen J, Cristofaro P, Carlet J, Opal S. New method of classifying infections in critically ill patients. Crit Care Med. 2004;32(7):1510鈥?6. CrossRef
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Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum beta-lactamases: a systematic review and meta-analysis. J Antimicrob Chemother. 2012;67(12):2793鈥?03. CrossRef 7. Rodriguez-Bano J, Navarro MD, Retamar P, Picon E, Pascual A. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012;54(2):167鈥?4. CrossRef 8. Peralta G, Lamelo M, Alvarez-Garcia P, Velasco M, Delgado A, Horcajada JP, et al. Impact of empirical treatment in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. bacteremia. A multicentric cohort study. BMC Infect Dis. 2012;12:245. CrossRef 9. McLaughlin M, Advincula MR, Malczynski M, Qi C, Bolon M, Scheetz MH. Correlations of antibiotic use and carbapenem resistance in Enterobacteriaceae. Antimicrob Agents Chemother. 2013;57(10):5131鈥?. CrossRef 10. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis. 2011;53(1):60鈥?. CrossRef 11. Boucher HW, Talbot GH, Benjamin Jr DK, Bradley J, Guidos RJ, Jones RN, et al. Infectious Diseases Society of A: 10鈥壝椻€夆€?0 progress-development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(12):1685鈥?4. CrossRef 12. Drawz SM, Papp-Wallace KM, Bonomo RA. New beta-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother. 2014;58(4):1835鈥?6. CrossRef 13. Tam VH, Ledesma KR, Chang KT, Wang TY, Quinn JP. Killing of Escherichia coli by beta-lactams at different inocula. Diagn Microbiol Infect Dis. 2009;64(2):166鈥?1. CrossRef 14. Rice LB, Carias LL, Hujer AM, Bonafede M, Hutton R, Hoyen C, et al. High-level expression of chromosomally encoded SHV-1 beta-lactamase and an outer membrane protein change confer resistance to ceftazidime and piperacillin-tazobactam in a clinical isolate of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2000;44(2):362鈥?. CrossRef 15. Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev. 2009;22(1):161鈥?2. CrossRef 16. Chen YH, Hsueh PR, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, et al. Antimicrobial susceptibility profiles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region according to currently established susceptibility interpretive criteria. J Infect. 2011;62(4):280鈥?1. CrossRef 17. Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev. 2012;25(4):682鈥?07. CrossRef 18. Rodriguez-Bano J, Navarro MD, Retamar P, Picon E, Pascual A. Extended-Spectrum Beta-Lactamases-Red Espanola de Investigacion en Patologia Infecciosa/Grupo de Estudio de Infeccion Hospitalaria G. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012;54(2):167鈥?4. CrossRef 19. Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG, Group C. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012;308(24):2594鈥?04. CrossRef 20. Breakpoint tables for interpretation of MICs and zone diameters version 4.0. Available from: http://www.eucast.org. Accessed 6th December 2014. 21. Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, et al. International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial Infections. Ann Intern Med. 2004;140(1):26鈥?2. CrossRef 22. Chow S-C, Hansheng W, Shao J. Sample size calculations in clinical research. 2nd ed. Boca Raton: Chapman Hall; 2007. 23. Harris PNA, Mo Y, Jureen R, Chew J, Ali J, Paterson DL, Tambyah PA. Meropenem and piperacillin-tazobactam have comparable outcomes in treatment of bloodstream infections caused by extended spectrum beta-lactamase producing E.coli and Klebsiellae. Abstract number 486, IDWeek. Philadelphia, PA: 8 to 12 October 2014. Available from: https://idsa.confex.com/idsa/2014/webprogram/Paper46679.html. Accessed 12th Jan 2015. 24. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance. Available from: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_v1.0_20131211.pdf. Accessed 26th Jan 2015. 25. Paterson DL. Determining research priorities for clinician-initiated trials in infectious diseases. Med J Aust. 2013;198(5):270鈥?. CrossRef 26. Spellberg B, Bartlett JG, Gilbert DN. The future of antibiotics and resistance. N Engl J Med. 2013;368(4):299鈥?02. CrossRef
- 刊物主题:Medicine/Public Health, general; Biomedicine general; Statistics for Life Sciences, Medicine, Health Sciences;
- 出版者:BioMed Central
- ISSN:1745-6215
文摘
Background Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections. Methods/Design The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection. Trial registration The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).
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