7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial

被引：32

作者：

Daneman, Nick ^{[1
,2
]}

Rishu, Asgar H. ^{[3
]}

Pinto, Ruxandra ^{[3
]}

Aslanian, Pierre ^{[4
,5
]}

Bagshaw, Sean M. ^{[6
]}

Carignan, Alex ^{[7
]}

Charbonney, Emmanuel ^{[8
,9
]}

Coburn, Bryan ^{[10
]}

Cook, Deborah J. ^{[11
]}

Detsky, Michael E. ^{[12
]}

Dodek, Peter ^{[13
,14
,15
]}

Hall, Richard ^{[16
,17
]}

Kumar, Anand ^{[18
]}

Lamontagne, Francois ^{[19
,20
]}

Lauzier, Francois ^{[21
]}

Marshall, John C. ^{[22
,23
]}

Martin, Claudio M. ^{[24
]}

McIntyre, Lauralyn ^{[25
]}

Muscedere, John ^{[26
]}

Reynolds, Steven ^{[27
]}

Sligl, Wendy ^{[6
]}

Stelfox, Henry T. ^{[28
]}

Wilcox, M. Elizabeth ^{[29
]}

Fowler, Robert A. ^{[30
,31
]}

机构：

[1] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Infect Dis & Clin Epidemiol, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada

[2] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada

[3] Sunnybrook Hlth Sci Ctr, Dept Crit Care Med, Toronto, ON, Canada

[4] Ctr Hosp Univ Montreal, Serv Soins Intensifs, Montreal, PQ, Canada

[5] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada

[6] Univ Alberta, Fac Med & Dent, Dept Crit Care Med, Edmonton, AB, Canada

[7] Univ Sherbrooke, Dept Microbiol & Infect Dis, Sherbrooke, PQ, Canada

[8] Univ Montreal, Hop Sacre Coeur Montreal, Dept Crit Care Med, Montreal, PQ, Canada

[9] Univ Montreal, Hop Trois Rivieres, Montreal, PQ, Canada

[10] Univ Toronto, Div Infect Dis, Toronto, ON, Canada

[11] McMaster Univ, Dept Med, Div Crit Care Med, Hamilton, ON, Canada

[12] Sinai Hlth Syst, Dept Med, Div Crit Care, Toronto, ON, Canada

[13] St Pauls Hosp, Div Crit Care Med, Vancouver, BC, Canada

[14] St Pauls Hosp, Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC, Canada

[15] Univ British Columbia, Vancouver, BC, Canada

[16] Univ Manitoba, Dept Crit Care Med, Pain Management & Perioperat Med, Halifax, NS, Canada

[17] Univ Manitoba, Dept Anesthesiol, Pain Management & Perioperat Med, Halifax, NS, Canada

[18] Univ Manitoba, Sect Crit Care Med, Winnipeg, MB, Canada

[19] Univ Sherbrooke, CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ, Canada

[20] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada

[21] Univ Laval, CHU Quebec, Ctr Rech, Div Soins Intensifs,Axe Sante Populat & Prat Opti, Quebec City, PQ, Canada

[22] Univ Toronto, St Michaels Hosp, Dept Surg, Toronto, ON, Canada

[23] Univ Toronto, St Michaels Hosp, Dept Crit Care Med, Toronto, ON, Canada

[24] Univ Western Ontario, Dept Med, London, ON, Canada

[25] Ottawa Hosp, Dept Med, Div Crit Care, Ottawa, ON, Canada

[26] Queens Univ, Dept Crit Care Med, Kingston, ON, Canada

[27] Simon Fraser Univ, Dept Biophysiol & Kinesiol, Burnaby, BC, Canada

[28] Univ Calgary, Inst Publ Hlth, Dept Crit Care Med, Calgary, AB, Canada

[29] Toronto Western Hosp, Dept Med, Div Crit Care, Toronto, ON, Canada

[30] Univ Toronto, Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Inst Hlth Policy Management & Evaluat,Dept Med, Toronto, ON, Canada

[31] Univ Toronto, Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Inst Hlth Policy Management & Evaluat,Dept Critic, Toronto, ON, Canada

来源：

TRIALS | 2018年 / 19卷

关键词：

Bacteremia; Bloodstream infection; Critical care; Intensive care; Duration of treatment; INTENSIVE-CARE UNITS; ACUTE PYELONEPHRITIS; DOUBLE-BLIND; ANTIMICROBIAL TREATMENT; OPEN-LABEL; DURATION; MULTICENTER; PNEUMONIA; THERAPY; PROCALCITONIN;

D O I：

10.1186/s13063-018-2474-1

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. Methods: We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1: 1 to intervention arms consisting of two fixed durations of treatment -7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms. Results: We successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3-1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascularcatheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8-17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days. Conclusion: It is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival.

引用

页数：9

共 27 条

[1] The design and interpretation of pilot trials in clinical research in critical care [J].

Arnold, Donald M. ;

Burns, Karen E. A. ;

Adhikari, Neill K. J. ;

Kho, Michelle E. ;

Meade, Maureen O. ;

Cook, Deborah J. .

CRITICAL CARE MEDICINE, 2009, 37 (01) :S69-S74

[2]

Awasthi S, 2004, BMJ-BRIT MED J, V328, P791

[3] Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial [J].

Bouadma, Lila ;

Luyt, Charles-Edouard ;

Tubach, Florence ;

Cracco, Christophe ;

Alvarez, Antonio ;

Schwebel, Carole ;

Schortgen, Frederique ;

Lasocki, Sigismond ;

Veber, Benoit ;

Dehoux, Monique ;

Bernard, Maguy ;

Pasquet, Blandine ;

Regnier, Bernard ;

Brun-Buisson, Christian ;

Chastre, Jean ;

Wolff, Michel .

LANCET, 2010, 375 (9713) :463-474

[4] Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults - A randomized trial [J].

Chastre, J ;

Wolff, M ;

Fagon, JY ;

Chevret, S ;

Thomas, F ;

Wermert, D ;

Clementi, E ;

Gonzalez, J ;

Jusserand, D ;

Asfar, P ;

Perrin, D ;

Fieux, F ;

Aubas, S .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (19) :2588-2598

[5]

Daneman N, 2016, JAMMI, V1, P33

[6] Duration of Antimicrobial Treatment for Bacteremia in Canadian Critically Ill Patients [J].

Daneman, Nick ;

Rishu, Asgar H. ;

Xiong, Wei ;

Bagshaw, Sean M. ;

Dodek, Peter ;

Hall, Richard ;

Kumar, Anand ;

Lamontagne, Francois ;

Lauzier, Francois ;

Marshall, John ;

Martin, Claudio M. ;

McIntyre, Lauralyn ;

Muscedere, John ;

Reynolds, Steve ;

Stelfox, Henry T. ;

Cook, Deborah J. ;

Fowler, Robert A. .

CRITICAL CARE MEDICINE, 2016, 44 (02) :256-264

[7] Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE): study protocol for a pilot randomized controlled trial [J].

Daneman, Nick ;

Rishu, Asgar H. ;

Xiong, Wei ;

Bagshaw, Sean M. ;

Cook, Deborah J. ;

Dodek, Peter ;

Hall, Richard ;

Kumar, Anand ;

Lamontagne, Francois ;

Lauzier, Francois ;

Marshall, John C. ;

Martin, Claudio M. ;

McIntyre, Lauralyn ;

Muscedere, John ;

Reynolds, Steven ;

Stelfox, Henry T. ;

Fowler, Robert A. .

TRIALS, 2015, 16

[8] Antibiotic treatment duration for bloodstream infections in critically ill patients: a national survey of Canadian infectious diseases and critical care specialists [J].

Daneman, Nick ;

Shore, Kevin ;

Pinto, Ruxandra ;

Fowler, Rob .

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2011, 38 (06) :480-485

[9] Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study [J].

de Smet, Anne Marie G. A. ;

Kluytmans, Jan A. J. W. ;

Blok, Hetty E. M. ;

Mascini, Ellen M. ;

Benus, Robin F. J. ;

Bernards, Alexandra T. ;

Kuijper, Ed J. ;

Leverstein-van Hall, Maurine A. ;

Jansz, Arjan R. ;

de Jongh, Bartelt M. ;

van Asselt, Gerard J. ;

Frenay, Ine H. M. E. ;

Thijsen, Steven F. T. ;

Conijn, Simon N. M. ;

Kaan, Jan A. ;

Arends, Jan P. ;

Sturm, Patrick D. J. ;

Bootsma, Martin C. J. ;

Bonten, Marc J. M. .

LANCET INFECTIOUS DISEASES, 2011, 11 (05) :372-380

[10] Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation [J].

Dethlefsen, Les ;

Relman, David A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 :4554-4561

← 1 2 3 →