Supplemental Material
Table 1:
Data Completeness Process of Care Variables
Table 2:
Infection rate (patient month) by procedure type
Table 3:
Minor Infections
Table 4:
Multivariable Model – Mortality
Figure 1:
Consort Diagram
APPENDIX I
DEFINITIONS OF MAJOR INFECTIONS
APPENDIX II
CTSN Members
1
Table 1: Data Completeness Process of Care Variables
Variable
Nasal Decontamination
Hair Removal (Males only)
Scrubbing Surgical Site
Central Lines
Femoral
Appropriate Timing of
Preoperative Antibiotics
Intraoperative Antibiotic ReDosed after 6 hrs
Type of Perioperative Antibiotics
Postoperative Antibiotic
Duration
Packed Red Blood Cells
Venue of Urinary Catheter
Insertion
Nasogastric Tube Used
Glucose Management
Mechanical Ventilation
Elevation of Head of Bed
Routine Aspiration of Secretions
2
Available
Data
5153
3450
5081
5158
5158
5121
%
99.90
100.0
98.51
100.0
100.0
99.28
5157
99.98
5158
5158
100.0
100.0
5158
5140
100.0
99.65
5157
5151
5154
5157
5156
99.98
99.86
99.92
99.98
99.96
Table 2: Infection rate (patient month) by procedure type
Infection Rate
(Per Patient Month)
0.017
0.022
0.034
0.171
0.037
0.033
Procedure
Isolated CABG
Isolated valve
CABG + valve
LVAD/Tx
Thoracic aorta surgery
Othera
Abbreviations: CABG, coronary artery bypass graft surgery; LVAD/Tx, left ventricular assist device or
transplant surgery.
a
Other: ventricular septal defect repairs, atrial septal defect repairs, aneurysmectomies, PFO closures,
ablations, septal myectomies, excision of cardiac tumors, pericardiectomies, and limited other procedures
3
Table 3: Minor Infections
# of
# of
% of Patients
Type of Infection
Events
Patients
(N=5158)
Symptomatic UTI
181
174
3.37
Superficial Incision SSI (chest)a
140
137
2.93
a
Superficial Incision SSI (groin)
73
73
1.56
Asymptomatic Bacteriuria
68
66
1.28
Otherb
4
4
0.08
a
Denominator for patients with a deep SSI is patients having a sternotomy (N=4669)
b
Other: cellulitis and three cases of tracheobronchitis
4
Days from surgery to first infection
Median
Min
Max
11
0
63
23
2
61
16.5
5
65
11.5
0
60
28.5
6
60
Table 4: Multivariable Model – Mortality
Variable
HR (95% CI)
Infection
10.02 (6.12, 16.39)
Age
1.04 (1.02, 1.06)
Male
0.49 (0.33, 0.72)
Diabetes
1.65 (1.08, 2.51)
Heart Failure
2.01 (1.34, 3.00)
Creatinine
1.17 (1.06, 1.29)
Abbreviations: HR, hazard ratio; CI, confidence interval
5
P Value
<.001
<.001
<.001
0.02
<.001
0.001
Figure 1: Consort Diagram
6
APPENDIX I DEFINITIONS OF MAJOR INFECTIONSa
Primary Endpoint
The primary endpoint is major infection following cardiac surgery. Major infection type and its
definitions are outlined below:
Bloodstream infection
A BSI must meet at least 1 of the following criteria:
1. Patient has a recognized pathogen cultured from 1 or more blood cultures and organism
cultured from blood is not related to an infection at another site
2. Patient has at least 1 of the following signs or symptoms: fever (>38°C), chills, or
hypotension and signs and symptoms and positive laboratory results are not related to an
infection at another site and common skin contaminant (ie, diphtheroids, Bacillus spp,
Propionibacterium spp, coagulase-negative staphylococci, viridians group streptococci,
Aerococcus spp, Micrococcus spp) is cultured from 2 or more blood cultures drawn on
separate occasions
Cardiac device infection
A cardiac device infection must meet at least 1 of the following criteria:
1. A positive culture from the skin and/or tissue surrounding a percutaneous cable, coupled
with the need to treat with antimicrobial therapy, when there is clinical evidence of
infection, such as pain, fever, drainage, or leukocytosis (percutaneous)
__________________________
a
Most infection definitions have been adapted from the CDC/NHSN surveillance definition of health care-
associated infection (www.cdc.gov/ncidod/ dhqp/nhsn.html).
7
2. A positive culture from the tissue surrounding the generator pocket, electrode leads, or
external housing of a device implanted within the body, coupled with the need to treat
with antimicrobial therapy, when there is clinical evidence of infection, such as pain,
fever, drainage, or leukocytosis (pocket)
3. Infection of blood-contacting surfaces of an LVAD documented by positive site culture
(pump component)
Clostridium difficile colitis
The presence of moderate to severe diarrhea or ileus, and either:
1.
A stool test positive for C. difficile toxins or toxigenic C. difficile
2.
Endoscopic or histologic findings of pseudomembranous colitis
Deep incisional surgical site infection, primary
A SSI that is identified in the primary chest incision and meets all of the following criteria:
1. Infection occurs within 60 days after the operative intervention
2. Infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision
3. Patient has at least 1 of the following:
a. Purulent discharge from the deep incision but not from the organ/space
component of the surgical site
b. A deep incision spontaneously dehisces or is deliberately opened by a surgeon
and is culture positive or not culturedb when the patient has at least 1 of the
following signs or symptoms: fever (>38°C), localized pain or tenderness
__________________________
b
A culture-negative finding does not meet this criterion.
8
c. An abscess or other evidence of infection involving the deep incision is found on
direct examination, during reoperation, or by histopathologic or radiologic
examination
d. Diagnosis of deep incisional SSI by the surgeon or attending physician
Deep incisional surgical site infection, secondary
A SSI that is identified in the secondary incision (e.g., donor site [leg] incision for CABG) in a
patient who has had an operation with 1 or more incisions and meets all of the following criteria:
1. Infection occurs within 60 days after the operative intervention
2. Infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision
3. Patient has at least 1 of the following:
a. Purulent discharge from the deep incision but not from the organ/space
component of the surgical site
b. A deep incision spontaneously dehisces or is deliberately opened by a surgeon
and is culture positive or not culturedb when the patient has at least 1 of the
following signs of symptoms: fever (>38°C), or localized pain or tenderness
c. An abscess or other evidence of infection involving the deep incision is found on
direct examination, during reoperation, or by histopathologic or radiologic
examination
d. Diagnosis of deep incisional SSI by the surgeon of attending physician
__________________________
b
A culture-negative finding does not meet this criterion.
9
Empyema
Pyothorax (empyema thoracis) is the accumulation of pus within the pleural cavity. Empyema
can occur in the setting of thoracic surgery, instrumentation of the pleural space (thoracentesis,
chest tube placement, etc), and suppurative lung disease (ie, pneumonia, lung abscess, or
bronchiectasis), among others. Empyema is characterized by bacterial organisms seen on gram
stain or the aspiration of pus on thoracentesis. A positive culture is not required for diagnosis,
since there are several reasons why bacteria may not be cultured from an empyema: anaerobic
organisms are difficult to culture, sampling is often performed after a patient has received
antibiotics, and sterile inflammatory fluid can be aspirated adjacent to an infected loculus of
infection.
Endocarditis
Endocarditis of a natural or prosthetic heart valve must meet at least 1 of the following criteria:
1. Direct evidence of endocarditis based upon histological findings
2. Positive Gram stain results or cultures of specimens obtained from surgery or autopsy
3. Two major clinical criteria
4. One major and any three minor clinical criteria
5. Five minor clinical criteria
Major Clinical Criteria:
1. Positive blood cultures
a. Typical microorganism for infective endocarditis from two separate blood
cultures
b. Persistently positive blood culture, defined as recovery of a microorganism
consistent with infective endocarditis from blood cultures drawn more than 12
10
hours apart or all of three or a majority of four or more separate blood cultures,
with first and last drawn at least one hour apart
c. Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody
titer > 1:800
2. Evidence of endocardial involvement
a. Positive echocardiogram for infective endocarditis
b. New valvular regurgitation
Minor Clinical Criteria:
1. Predisposition
a. Predisposing heart condition
b. Intravenous drug use
2. Fever – 38°C
3. Vascular phenomena
a. Major arterial emboli
b. Septic pulmonary infarcts
c. Mycotic aneurysm
d. Intracranial hemorrhage
e. Conjunctival hemorrhages
f.
Janeway lesions
4. Immunologic phenomena
a. Glomerulonephritis
b. Osler’s nodes
c. Roth spots
d. Rheumatoid factor
5. Microbiologic evidence
11
a. Positive blood culture but not meeting major criterion as noted previously
b. Serologic evidence of active infection with organism consistent with infective
endocarditis
6. Echocardiographic minor criteria eliminated
Infectious myocarditis or pericarditis
Infectious myocarditis or pericarditis must meet at least 1 of the following criteria:
1. Patient has organisms cultured from pericardial tissue or fluid obtained by needle
aspiration or during a surgical operation
2. Patient has at least 2 of the following signs or symptoms with no other recognized cause:
fever (>38°C), chest pain, paradoxical pulse, or increased heart size and at least 1 of the
following:
a. Abnormal EKG consistent with myocarditis or pericarditis
b. Positive antigen test on blood (e.g., H. influenzae, S. pneumoniae)
c. Evidence of myocarditis or pericarditis on histologic examination of heart tissue
d. 4-fold rise in type-specific antibody with or without isolation of virus from
pharynx or feces
e. Pericardial effusion identified by echocardiogram, CT scan, MRI, or angiography
Mediastinitis
Mediastinitis must meet at least 1 of the following criteria:
1. Patient has organisms cultured from mediastinal tissue or fluid obtained during a surgical
operation or needle aspiration
2. Patient has evidence of mediastinitis seen during a surgical operation or histopathologic
examination
12
3. Patient has at least 1 of the following signs or symptoms with no other recognized cause:
fever (>38°C), chest pain, or sterna instability and at least 1 of the following:
a. Purulent discharge from mediastinal area
b. Organisms cultured from blood or discharge from mediastinal area
Pneumonia
Clinically defined pneumonia must meet all of the following criteria:
1. At least one or more chest radiographs no earlier than two days post-surgery with at least
1 of the following:
a. New or progressive and persistent infiltrate
b. Consolidation
c. Cavitation
2. Patient has at least 1 of the following signs or symptoms: fever (>38°C) with no other
recognized cause, leukopenia (<4,000 WBC/mm3) or leukocytosis (≥12,000 WBC/mm3),
or altered mental status with no other recognized cause (for patients ≥ 70 years old) and
at least 2 of the following:
a. New onset of purulent sputum or change in character or sputum or increased
respiratory secretions or increased suctioning requirements
b. New onset or worsening cough, or dyspnea, or tachypnea
c. Rales or bronchial breath sounds
d. Worsening gas exchange (e.g. O2 desaturations, increased oxygen requirements,
or increased ventilator demand)
13
APPENDIX II
The members of the Cardiothoracic Surgical Trials Network (CTSN) involved in this study were as
follows:
National Heart, Lung and Blood Institute: Marissa A. Miller, Wendy C. Taddei-Peters, Dennis Buxton,
Ron Caulder, Nancy L. Geller, David Gordon, Neal O. Jeffries, Albert Lee;
National Institute of Neurological Disorders and Stroke: Claudia S. Moy;
Canadian Institutes of Health Research: Ilana Kogan Gombos, Jennifer Ralph;
Network Chairs: Christiana Care Health System, Timothy J. Gardner, (Chair); Brigham and Women’s
Hospital, Patrick T. O’Gara, (Co-Chair);
Data Coordinating Center: International Center for Health Outcomes and Innovation Research at
Icahn School of Medicine at Mount Sinai, Annetine C. Gelijns, Michael K. Parides, Deborah D. Ascheim,
Alan J. Moskowitz, Ellen Moquete, Eric A. Rose, Melissa Chase, Yingchun Chen, Rosemarie Gagliardi,
Lopa Gupta, Edlira Kumbarce, Ron Levitan, Karen O’Sullivan, Milerva Santos, Alan Weinberg, Paula
Williams, Carrie Wood, Xia Ye;
Core Clinical Site Investigators: Cleveland Clinic Foundation, Eugene H. Blackstone (PI), A. Marc
Gillinov, Pamela Lackner, Leoma Berroteran, Diana Dolney, Suzanne Fleming, Roberta Palumbo,
Christine Whitman, Kathy Sankovic, Denise Kosty Sweeney; NHLBI Clinical Research Scholars:
Gregory Pattakos, Pamela A. Clarke; Columbia University, Michael Argenziano (PI), Mathew Williams,
Lyn Goldsmith, Craig R. Smith, Yoshifumi Naka, Allan Stewart, Allan Schwartz; Daniel Bell, Danielle
Van Patten; Duke University, Peter K. Smith (PI), Stacey Welsh, John H. Alexander, Carmelo A. Milano,
Donald D. Glower, Joseph P. Mathew, J. Kevin Harrison; NHLBI Clinical Research Scholars: Mark F.
Berry, Cyrus J. Parsa, Betty C. Tong, Judson B. Williams; East Carolina Heart Institute, T. Bruce
Ferguson (PI), Alan P. Kypson, Evelio Rodriguez, Malissa Harris, Brenda Akers, Allison O'Neal; Emory
University, John D. Puskas (PI), Vinod H. Thourani, Robert Guyton, Jefferson Baer, Kim Baio, Alexis A.
Neill; Montefiore-Einstein Heart Center, New York, NY, Robert E. Michler (PI), David A. D'Alessandro,
Joseph J. DeRose, Jr., Daniel J. Goldstein, Ricardo Bello, William Jakobleff, Mario Garcia, Cynthia
14
Taub, Daniel Spevak, Roger Swayze; Montreal Heart Institute, Louis P. Perrault (PI), Arsène-Joseph
Basmadjian, Denis Bouchard, Michel Carrier, Raymond Cartier, Michel Pellerin, Jean François Tanguay,
Ismael El-Hamamsy, André Denault, Jonathan Lacharité, Sophie Robichaud; NIH Heart Center at
Suburban Hospital, Keith A. Horvath (PI), Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy,
Margaret Iraola, Ann Greenberg; University of Pennsylvania, Michael A. Acker (PI), Y. Joseph Woo,
Mary Lou Mayer; University of Virginia, Irving L. Kron (PI), Gorav Ailawadi, Karen Johnston, John M.
Dent, John Kern, Jessica Keim Sandra Burks, Kim Gahring;
Protocol Review Committee: David A. Bull (Chair); Patrice Desvigne-Nickens, Executive Secretary;
Dennis O. Dixon, Mark Haigney, Richard Holubkov, Alice Jacobs, Frank Miller, John M. Murkin, John
Spertus, Andrew S. Wechsler;
Data and Safety Monitoring Board: Frank Selke (Chair); Cheryl L. McDonald, Executive Secretary;
Robert Byington, Neal Dickert, Dennis O. Dixon, John S. Ikonomidis, David O. Williams, Clyde W.
Yancy;
Medical Monitors: James C. Fang, Wayne Richenbacher;
Overall Event Adjudication Committee: Vivek Rao (Chair); Karen L. Furie, Rachel Miller, Sean
Pinney, William C. Roberts;
Infection Event Adjudication Committee: Rachel Miller (Chair); Shirish Huprikar, Marilyn Levi.
15