Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study

被引:15
作者
Muscedere, John [1 ]
Maslove, David M. [1 ]
Boyd, J. Gordon [1 ]
O'Callaghan, Nicole [1 ]
Sibley, Stephanie [1 ]
Reynolds, Steven [2 ,3 ]
Albert, Martin [4 ,5 ]
Hall, Richard [6 ,7 ]
Jiang, Xuran [8 ]
Day, Andrew G. [8 ]
Jones, Gwyneth [9 ]
Lamontagne, Francois [10 ]
机构
[1] Queens Univ, Dept Crit Care Med, Kingston, ON, Canada
[2] Univ British Columbia, Dept Med, Vancouver, BC, Canada
[3] Simon Fraser Univ, Dept Biophysiol & Kinesiol, Burnaby, BC, Canada
[4] Univ Montreal, Crit Care Dept, Ctr Rech Hop Sacre Coeur Montreal, Montreal, PQ, Canada
[5] Univ Montreal, Dept Med, Ctr Rech Hop Sacre Coeur Montreal, Montreal, PQ, Canada
[6] Dalhousie Univ, Dept Crit Care Med, Halifax, NS, Canada
[7] Nova Scotia Hlth Author, Halifax, NS, Canada
[8] Kingston Gen Hosp, Kingston, ON, Canada
[9] Univ Ottawa, Dept Crit Care Med, Ottawa, ON, Canada
[10] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada
关键词
antibiotics; critically ill; lactoferrin; mechanical ventilation; nosocomial infections; VENTILATOR-ASSOCIATED PNEUMONIA; STAPHYLOCOCCUS-AUREUS; BIOFILM FORMATION; SEVERE SEPSIS; TALACTOFERRIN; TRIAL; SUPPLEMENTATION; IMMUNE; IRON; CARE;
D O I
10.1097/CCM.0000000000003294
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [sd], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial.
引用
收藏
页码:1450 / 1456
页数:7
相关论文
共 36 条
[1]  
Aguila A, 2001, FEMS IMMUNOL MED MIC, V31, P145, DOI 10.1111/j.1574-695X.2001.tb00511.x
[2]  
Brock JH, 2012, BIOCHEM CELL BIOL, V90, P245, DOI [10.1139/O2012-018, 10.1139/o2012-018]
[3]   Impact of nosocomial infections on clinical outcome and resource consumption in critically ill patients [J].
Burgmann, Heinz ;
Hiesmayr, J. Michael ;
Savey, Anne ;
Bauer, Peter ;
Metnitz, Barbara ;
Metnitz, Philipp G. H. .
INTENSIVE CARE MEDICINE, 2010, 36 (09) :1597-1601
[4]   EPIDEMIOLOGY OF NOSOCOMIAL PNEUMONIA - NEW PERSPECTIVES ON AN OLD DISEASE [J].
CRAVEN, DE ;
STEGER, KA .
CHEST, 1995, 108 (02) :S1-S16
[5]   Biofilms and device-associated infections [J].
Donlan, RM .
EMERGING INFECTIOUS DISEASES, 2001, 7 (02) :277-281
[6]   KILLING OF GRAM-NEGATIVE BACTERIA BY LACTOFERRIN AND LYSOZYME [J].
ELLISON, RT ;
GIEHL, TJ .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 88 (04) :1080-1091
[7]   Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia -: A randomized trial [J].
Fagon, JY ;
Chastre, J ;
Wolff, M ;
Gervais, C ;
Parer-Aubas, S ;
Stéphan, F ;
Similowski, T ;
Mercat, A ;
Diehl, JL ;
Sollet, JP ;
Tenaillon, A .
ANNALS OF INTERNAL MEDICINE, 2000, 132 (08) :621-+
[8]   Immunoparalysis and adverse outcomes from critical illness [J].
Frazier, W. Joshua ;
Hall, Mark W. .
PEDIATRIC CLINICS OF NORTH AMERICA, 2008, 55 (03) :647-+
[9]   A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Talactoferrin in Patients With Severe Sepsis [J].
Guntupalli, Kalpalatha ;
Dean, Nathan ;
Morris, Peter E. ;
Bandi, Venkata ;
Margolis, Benjamin ;
Rivers, Emanuel ;
Levy, Mitchell ;
Lodato, Robert F. ;
Ismail, Preeti M. ;
Reese, Amber ;
Schaumberg, John P. ;
Malik, Rajesh ;
Dellinger, R. Phillip .
CRITICAL CARE MEDICINE, 2013, 41 (03) :706-716
[10]   Comparison of Bioactivities of Talactoferrin and Lactoferrins From Human and Bovine Milk [J].
Jiang, Rulan ;
Du, Xiaogu ;
Loennerdal, Bo .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2014, 59 (05) :642-652