SUPPLEMENTARY TABLES
Supplementary Table 1. Definitions of device-related infection in the included studies.
Study ID
Definition
Muers 1981
Oral temperature of 37.5°C on ≥2 occasions on or after the 3 rd postoperative day with evidence of acute
inflammation and of pus or bacteria in the generator pouch; or frank pus in the generator pocket. Erosion with
secondary infection was excluded.
Ramsdale 1984
Pocket infection: oral temperature of ≥37.5°C on ≥2 occasions on or after the 3rd postoperative day associated
with acute inflammation around the generator and/or pus in the generator pocket. Superficial wound infection:
indurated discharging and nondischarging wound edges without evidence of pocket infection, requiring
antibiotic treatment but not generator replacement.
Bluhm 1984
Presence of purulent substance and/or increased local temperature, redness, pain and swelling.
2728272828
Bluhm 1986
Purulent secretion; or ≥2 inflammatory signs of local temperature rise, redness, pain and swelling together with
a positive culture; or all 4 inflammatory signs without positive culture. Erosion of generator/lead was excluded.
Glieca 1987
Fever (>37.5°C) with local signs of inflammation or purulent secretion at the pocket site. Positive cultures were
found in all cases.
Mueller 1990
Criteria proposed by Choo et el.: 1) Inflammation and abscess formation at the implant site. 2) Erosion of the
pacing system with secondary infection. 3) Fever and positive blood cultures without any other source of
infection. Positive cultures from the infected site essential for the diagnosis of infection.
Bru 1991
Local signs of inflammation at the pocket associated with ≥1of the following: positive cultures, purulent
secretion or general signs of infection.
Lüninghake 1993
Microbiologically proven infection and local aseptic inflammation.
Mounsey 1994
Septicaemia, pocket abscess, or erosion of the pulse generator or electrode through the skin; all requiring a
repeat operation.
Chauhan 1994
Criteria proposed by Choo et al.
Aggarwal 1995
Pocket infection requiring generator/lead removal. Superficial infection requiring only antibiotics was
excluded.
Kron 2003
Device infections requiring hospitalization or prolongation of hospitalization with or without explantation and
administration of intravenous antibiotics.
Bertaglia 2006
Major infective complications: septicemia, endocarditis, pocket abscess, or pocket erosion.
Klug 2007
1) Fistula, abscess, or purulent collection at the site of the implanted material; 2) impending/frank erosion
associated with fever or with a major Duke criterion; 3) systemic infection related to CIED: Duke criteria.
Oliveira 2009
Superficial infection: local inflammation and pus in the surgical incision without evidence of pocket extension
or systemic manifestation. Pocket infection without systemic manifestation: purulent discharge with
microorganisms demonstrated by culture from the surgical wound or pocket with ≥2 of the following: pain,
warmth, erythema, or local fluctuance. Systemic infection: pocket infection with ≥2of the following: fever,
hypothermia, tachycardia, tachypnea, leukocytosis, leukopenia.
Romeyer-Bouchard
Definition of Mayo Cardiovascular Infections Study Group.
2010
Krahn 2011
Major pocket infections usually requiring intervention; minor incisional infections.
Metais 2011
Surgical site infection: pus discharge from the wound within 1 year after implantation, irrespective of
microorganism identification or deep infection of the surgical site. CIED-endocarditis or infection of the leads
was confirmed by transesophageal echocardiography in case of any suspicious biological or clinical symptoms.
Landolina 2011
NR
MacFadden 2012
Major pocket infections usually requiring intervention; minor incisional infections.
Uslan 2012
CDC definition for surgical site infections including deep and superficial surgical site infections exclusive of
stitch abscesses.
Bloom 2006
Infection requiring device explantation.
Sohail 2007
Definition of Mayo Cardiovascular Infections Study Group: pocket infection: local signs of inflammation
(erythema, warmth, fluctuance, wound dehiscence, tenderness, purulent drainage, or erosion of generator or
lead through skin) and positive cultures; or positive blood cultures without any other source of bacteremia and
resolution of bacteremia after device extraction. Endocarditis: valvular or lead vegetations in echocardiography
or Duke criteria for infective endocarditis.
Marschall 2007
CDC definition for surgical site infections (superficial incisional, deep incisional, or organ space infections).
Lekkerkerker 2008
Definition of Mayo Cardiovascular Infections Study Group.
Gould 2008
Pocket infections requiring lead extraction and incisional infections treated medically.
Nery 2010
Modified Mayo Clinic group definition including superficial wound infections.
Sohail 2011
Definition of Mayo Cardiovascular Infections Study Group.
Raad 2012
Pocket infection: local warmth, erythema, swelling, edema, pain, or discharge from the device pocket.
Unexplained bloodstream infection or sepsis in a patient with CIED. Lead-related endocarditis: vegetations in
transesophageal echocardiography or positive Duke criteria.
Hercé 2013
≥1 of the following criteria requiring explantation of the device: positive culture from the explanted material;
local signs of inflammation (abscess, fistula, discharge), with or without general signs of infection (fever,
elevated CRP, leukocytosis) or positive blood culture; presence of lead or valvular vegetations in
echocardiography; repeated septic pulmonary embolism, suggestive of device-related infection.
Rao 1974
NR
Mugica 1977
Abscess formation.
Hartstein 1978
Purulent secretion at the generator site with positive cultures.
Wunderly 1990
Local erythema, tenderness or swelling at the generator site and positive wound cultures or purulent drainage
with a positive wound gram stain.
Trappe 1995
Local signs of inflammation (warmth, erythema, purulent drainage), general signs of inflammation (fever
[>37.5°C], leukocytosis, a shift of the differential blood count to the left, elevated serum CRP) and positive
blood cultures.
Spinler 1998
Presence of fever (>100.4 F), leukocytosis (WBC>104/mm3) and other signs and symptoms dependent on the
site of infection, with or without positive aspirate or blood cultures.
Smith 1998
NR
Harcombe 1998
Late (>6 weeks after implantation) infective complications according to Choo et al.
Kiviniemi 1999
Criteria proposed by Choo et al.
Higgins 2000
NR
Mela 2001
NR
Wiegand 2004
NR
Al-Khatib 2005
NR
Gil 2006
Fever (> 37.8°C) or any sign of infection (warmth, erythema, tenderness, purulent drainage) around the pocket
or surgical wound.
Catanchin 2007
1) Pocket infection: clinical signs with or without positive cultures, abscess formation and wound breakdown.
2) Lead infection: clinical features with or without positive blood cultures or vegetations in echocardiography.
Dasgupta 2007
Pocket infection requiring device extraction.
Ito 2009
Infective endocarditis (definition not reported).
Pakarinen 2010
1) Device system infection (pocket infection or fever associated with positive blood cultures without an
infectious focus elsewhere). 2) Superficial wound infection.
Cengiz 2010
1) Pocket infection. 2) Systemic infection (valvular or lead vegetations in echocardiography or modified Duke
criteria for endocarditis).
Borleffs 2010
Infectious pocket-related causes of surgical reintervention: 1) pocket infection (confirmed invasion of
pathogenic microorganisms within the ICD pocket); 2) decubic ulcer (impending or frank erosions without
apparent infectious manifestations).
Margey 2010
Definition of Mayo Cardiovascular Infections Study Group.
Bloom 2011
1) Superficial incisional surgical site infection according to CDC. 2) Deep incisional or organ/space (generator
pocket) surgical site infection. 3) Endocarditis: modified Duke criteria.
Johansen 2011
A record of ‘infection’, ‘mechanical protrusion’, ‘erosion’, or ‘wound pain’ treated with device removal.
Charytan 2011
ICD-9 diagnosis 996.61. Device infections were further validated by evidence of intravenous antibiotic use,
hospitalization, device or lead removal within 30 days, or subsequent death.
Tompkins 2011
Definite infection of the pocket or lead (positive cultures) or development of bacteremia/ sepsis within 60 days
of implantation.
Lyman 2011
NR
Armaganijan 2012
NR
Schuchert 2013
NR
Peterson 2013
NR
Palmisano 2013
1) Systemic infection: valvular or lead vegetations in echocardiography or modified Duke criteria for infective
endocarditis. 2) Pocket infection: swelling, redness, and discharge in the pocket and bacterial growth in wound
cultures without evidence of systemic infection.
CIED cardiac implantable electronic device, NR not reported, CDC centers for disease control and prevention, CRP C-reactive
protein, WBC white blood cells, ICD implantable cardioverter-defibrillator, ICD-9 international classification of diseases (ninth
revision)
Supplementary Table 2. Microbiology of device-related infections.
Study ID
Na
Microorganism b
Muers 1981 33
9
Staphylococcus aureus (S. aureus): 44%; Staphylococcus epidermidis (S. epidermidis): 11%; negative:
44%
Ramsdale 1984 34
21
S. aureus: 19%; Clostridium welchii: 5%; polymicrobial: 5%; negative: 24%; no specimen: 48%
Bluhm 1984 27
8
S. aureus: 25%; S. epidermidis: 38%; unknown: 38%
Glieca 1987 30
12
S. aureus: 25%; S. epidermidis: 67%; Escherichia coli (E. coli): 8%
Mueller 1990 45
3
S. epidermidis: 100%
Lüninghake 1993 31
15
S. aureus: 7%; negative: 93%
Mounsey 1994 32
13
S. aureus: 31%; S. epidermidis: 8%; Enterococcus faecalis: 8%; skin flora: 31%; E. coli: 8%; negative:
15%
Bertaglia 2006 36
15
S. aureus: 7%; negative: 33%; unknown: 60%
Klug 2007 39
42
S. aureus: 14%; S. epidermidis: 29%; CoNS: 21%; Corynebacterium: 2%; Morganella morganii: 2%;
Staphylococcus schleiferi: 2%; E. coli: 2%; polymicrobial: 7%; negative/unknown: 19%
Oliveira 2009 29
13
S. aureus: 62% (MRSA: 12.5%; MSSA: 87.5%); S. epidermidis: 23%; Staphylococcus simulans: 8%;
CoNS: 8%
Romeyer-Bouchard
13
S. aureus: 54% (MSSA 100%); CoNS: 15%; Gram-negative: 8%; negative: 23%
Metais 2011 44
7
S. aureus: 29% (MRSA: 50%; MSSA: 50%); S. epidermidis: 29%; CoNS: 29%; unknown: 14%
Uslan 2012 47
14
S. aureus: 14%; CoNS: 14%; negative: 36%; Serratia marcescens: 7%; E. coli: 7%; Acinetobacter
2010
46
baumannii: 7%; Citrobacter koseri: 7%; Propionibacterium acnes: 7%
Sohail 2007 15
29
S. aureus: 38% (MRSA: 18%; MSSA: 82%); CoNS: 31%; Gram-negative: 3%; Candida albicans: 3%;
Aspergillus fumigates: 3%; Peptostreptococcus magnus: 3%; polymicrobial: 7%; negative: 10%
Marschall 2007 51
19
S. aureus: 11%; CoNS: 11%; Serratia marcescens: 5%; negative: 11%; no specimen: 63%
Lekkerkerker 2008
75
S. aureus: 25%; CoNS: 29%; other bacteria: 11%; polymicrobial: 13%; negative: 15%; no specimen: 6%
24
S. aureus: 21%; CoNS: 13%; Viridans group streptococci: 4%; Serratia marcescens: 4%; Pseudomonas
50
Nery 2010 52
species: 4%; negative: 54%
Sohail 2011 14
68
S. aureus: 47% (MRSA: 28%; MSSA: 72%); CoNS: 25%; polymicrobial: 7%; Serratia marcescens: 6%;
Propionibacterium species: 4%; Enterococcus species: 1%; Pseudomonas aeruginosa: 1%; negative: 7%
Raad 2012 53
18
S. aureus: 11%; S. epidermidis: 28%; CoNS: 6%; Morganella morganii: 6%; Proteus mirabilis: 6%;
negative: 28%; unknown: 17%
Hercé 2013 49
35
S. aureus: 34%; other: 29%; negative: 37%
Rao 1974 71
3
S. aureus: 33%; E. coli: 33%; polymicrobial: 33%
Mugica 1977
40
S. aureus: 61.5%; S. epidermidis: 33.5%; negative: 5.5%
Hartstein 1978 64
9
S. aureus: 33%; S. epidermidis: 44%; Micrococcus: 11%; polymicrobial: 11%
Wunderly 1990 76
8
S. aureus: 38%; S. epidermidis: 25%; Corynebacterium species: 25%; negative: 13%
Trappe 1995 75
13
S. aureus: 46%; CoNS: 31%; Pseudomonas species: 15%; Streptococcus pyogenes: 8%
Spinler 1998 11
9
S. aureus: 44% (MSSA: 100%); CoNS: 33%; Pseudomonas aeruginosa: 11%; negative: 11%
Smith 1998 73
19
S. aureus: 26%; CoNS: 26%; Staphylococcus (not otherwise specified): 5%; fungi: 11%; corynebacteria:
69
5%; Bacillus fragilis: 5%; negative: 21%
Harcombe 1998 63
18
S. aureus: 11%; S. epidermidis: 44%; Staphylococcus xylous: 5%; Enterobacter: 5%; Clostridium fallox:
5%; Pseudomonas aeruginosa: 5%; polymicrobial: 28%
Mela 2001 68
21
S. aureus: 38%; CoNS: 19%; Propionibacterium: 5%; polymicrobial: 29%; negative: 10%
Gil 2006 62
10
S. aureus: 10%; CoNS: 30%; Streptococcus agalactiae: 10%; polymicrobial: 40%; negative: 10%
Catanchin 2007 58
39
S. aureus: 38% (MRSA: 13%; MSSA: 87%); CoNS: 21% (methicillin-resistant: 13%); Gram-negative
bacillus: 3%; Gram-positive coccus: 3%; negative: 36%
Cengiz 2010 59
57
S. aureus: 12% (MRSA: 29%; MSSA: 71%); S. epidermidis: 11% (methicillin-resistant: 33%);
Staphylococcus hominis: 4%; Bacillus subspecies: 2%; Enterobacter cloacae: 4%; Acinetobacter
haemolyticus: 2%; Pseudomonas aeruginosa: 2%; negative/ unknown: 65%
Margey 2010 e 57
39
S. aureus: 36% (MRSA: 14%; MSSA: 86%); CoNS: 21%; Streptococcus species: 8%; Gram-negative:
5%; negative: 38%
Bloom 2011 84
3
CoNS: 33%; negative: 67%
Tompkins 2011 74
7
S. aureus: 57% (MRSA: 75%; MSSA: 25%); Enterococcus: 29%; polymicrobial: 14%
CoNS coagulase-negative Staphylococcus, MRSA methicillin-resistant Staphylococcus aureus, MSSA methicillin-susceptible
Staphylococcus aureus
a
b
Number of infections with available microbiological data.
Identified from pocket, lead or blood cultures.
Supplementary Table 3. Pooled effect estimates for potential risk factors predisposing to
CIED infection.
Factor
Studies Totals Statistical Pooled estimate
(N)
(N)
Method
Age
11
6295
WMD
-1.27 [-3.08, 0.55]
Male gender
16
18770
OR
BMI ≥ 25
3
367
Body weight
2
ASA ≥ 3
P value
Heterogeneity
P
I2
0.17
0.67
0
1.12 [0.89, 1.41]
0.35
0.50
0
OR
1.04 [0.63, 1.72]
0.87
0.36
2.01
453
WMD
-2.69 [-6.69, 1.31]
0.19
0.77
0
2
380
OR
0.93 [0.24, 3.58]
0.91
0.94
0
Smoking
2
1820
OR
0.48 [0.11, 2.08]
0.32
0.82
0
Diabetes mellitus
18
11839
OR
2.08 [1.62, 2.67]
<0.000001 0.37
6.83
Renal insufficiency a
5
2033
OR
3.02 [1.38, 6.64]
0.006
70.50
Host-related factors
0.01
ESRD b
8
3045
OR
8.73 [3.42, 22.31]
Serum Creatinine
4
612
WMD
Cirrhosis
2
291
Atrial fibrillation
6
CAD
0.00001
0.11
41
12.78 [-9.78, 35.33] 0.27
0.02
68.33
OR
1.94 [0.28, 13.53]
0.51
0.38
0
872
OR
1.12 [0.63, 1.98]
0.69
0.10
45.77
6
968
OR
1.26 [0.92, 1.73]
0.15
0.73
0
Previous MI
2
1948
OR
1.08 [0.41, 2.89]
0.87
0.06
72.19
CABG
3
363
OR
0.87 [0.54, 1.40]
0.56
0.74
0
CHF
6
1277
OR
1.65 [1.14, 2.39]
0.008
0.73
0
NYHA class ≥ 2
3
2447
OR
2.47 [1.24, 4.91]
0.01
0.61
0
Ejection fraction
4
2837
WMD
-0.78 [-3.32, 1.76]
0.55
0.74
0
Prosthetic valve
4
649
OR
1.42 [0.72, 2.81]
0.31
0.53
0
PAD
2
1948
OR
0.88 [0.31, 2.50]
0.81
0.28
16.06
Cerebrovascular disease
2
1948
OR
1.07 [0.30, 3.79]
0.91
0.06
71.36
COPD
6
2810
OR
2.95 [1.78, 4.90]
0.00003
0.91
0
Malignancy
6
1555
OR
2.23 [1.26, 3.95]
0.006
0.48
0
Autoimmune disease
2
291
OR
1.44 [0.42, 4.90]
0.56
0.32
0
Skin disorders
4
6810
OR
2.46 [1.04, 5.80]
0.04
0.34
9.73
Fever prior to implantation
3
6652
OR
4.27 [1.13, 16.12]
0.03
0.23
33.01
Oral anticoagulants
9
8527
OR
1.59 [1.01, 2.48]
0.04
0.06
45.89
Antiplatelet therapy
4
6748
OR
1.37 [0.83, 2.28]
0.22
0.54
0
Heparin bridging
2
6373
OR
1.87 [1.03, 3.41]
0.04
0.71
0
Corticosteroid use
10
3432
OR
3.44 [1.62, 7.32]
0.001
0.36
9.46
Immunosuppressive drug use c 2
291
OR
1.85 [0.63, 5.46]
0.27
0.49
0
Permanent CVC
3
1181
OR
5.74 [0.94, 34.93]
0.06
0.15
47.18
History of device infection
4
463
OR
7.84 [1.94, 31.60]
0.004
0.17
40.10
Antibiotic prophylaxis
16
14166
OR
0.32 [0.18, 0.55] d
0.00005
<0.001 62.61
Device replacement/
26
21214
OR
1.98 [1.46, 2.70]
0.00001
0.006
45.88
Generator change
20
12134
OR
1.74 [1.22, 2.49]
0.002
0.02
43.64
Lead dislodgement/
5
1755
OR
6.37 [2.93, 13.82]
0.000003
0.30
17.63
Hematoma
12
14228
OR
8.46 [4.01, 17.86]
<0.000001 0.001
63.66
Temporary pacing
10
10683
OR
2.31 [1.36, 3.92]
0.002
34.75
Procedure-related factors
revision/upgrade
repositioning
0.13
Procedure duration
9
4850
WMD
9.89 [0.52, 19.25]
0.04
0.008
61.59
Inexperienced operator e
2
1715
OR
2.85 [1.23, 6.58]
0.01
0.47
0
ICD device
14
16594
OR
1.19 [0.84, 1.68]
0.32
0.27
16.53
CRT device
9
13308
OR
1.92 [0.90, 4.10]
0.09
0.09
42.29
Dual-chamber device
14
45224
OR
1.45 [1.02, 2.05]
0.04
0.04
44.3
≥2 leads
6
1146
OR
2.02 [1.11, 3.69]
0.02
0.17
35.61
Abdominal generator pocket
7
4017
OR
4.01 [2.48, 6.49]
<0.000001 0.67
0
Presence of epicardial leads
3
623
OR
8.09 [3.46, 18.92]
0.000001
0.98
0
Presence of abandoned leads
2
291
OR
1.82 [0.86, 3.83]
0.12
0.51
0
Device-related factors
WMD weighted mean difference, OR odds ratio, BMI body mass index, ASA American Society of
Anesthesiologists, ESRD end-stage renal disease, CAD coronary artery disease, MI myocardial infarction, CABG
coronary artery bypass grafting, CHF congestive heart failure, NYHA New York Heart Association, PAD
peripheral artery disease, COPD chronic obstructive pulmonary disease, CVC central venous catheter, ICD
implantable cardioverter defibrillator, CRT cardiac resynchronization therapy.
a
Glomerular filtration rate (GFR) <60 ml/min or creatinine clearance (CrCL) <60 ml/min
GFR≤ 15 ml/min or hemodialysis or peritoneal dialysis
c
Immunosuppressive drugs other than corticosteroids
d
The pooled effect estimate from randomized studies was 0.26 [0.13, 0.52]
e
<100 previous procedures
b
Supplementary Table 4. Sensitivity analysis excluding studies that included superficial
wound infections and studies with inadequate definition of CIED infection.
Factor
Studies Totals Statistical Pooled estimate
(N)
(N)
Method
Age
4
1457
WMD
-0.07 [-2.82, 2.68]
Male gender
10
14444
OR
BMI ≥ 25
2
291
Body weight
2
Diabetes mellitus
P value
Heterogeneity
P
I2
0.96
0.32
14.34
1.26 [0.95, 1.66]
0.10
0.91
0
OR
0.94 [0.44, 2.01]
0.87
0.17
45.78
453
WMD
-2.69 [-6.69, 1.31]
0.19
0.77
0
12
9082
OR
2.00 [1.52, 2.64]
0.0000009 0.45
0
Renal insufficiency a
4
593
OR
2.64 [1.17, 5.97]
0.02
0.01
74.26
ESRD b
6
981
OR
6.27 [2.86, 13.75]
0.000005
0.66
0
Serum Creatinine
3
558
WMD
20.70 [-7.55, 48.94] 0.15
0.05
67.13
Cirrhosis
2
291
OR
1.94 [0.28, 13.53]
0.51
0.38
0
Atrial fibrillation
5
818
OR
1.33 [0.79, 2.25]
0.28
0.21
32.52
Host-related factors
CAD
6
968
OR
1.26 [0.92, 1.73]
0.15
0.73
0
CABG
3
363
OR
0.87 [0.54, 1.40]
0.56
0.74
0
CHF
4
515
OR
1.60 [1.08, 2.36]
0.02
0.52
0
Prosthetic valve
2
291
OR
1.14 [0.45, 2.92]
0.78
0.26
20
COPD
3
363
OR
3.35 [1.73, 6.50]
0.0004
0.92
0
Malignancy
6
1555
OR
2.23 [1.26, 3.95]
0.006
0.48
0
Autoimmune disease
2
291
OR
1.44 [0.42, 4.90]
0.56
0.32
0
Skin disorders
4
6810
OR
2.46 [1.04, 5.80]
0.04
0.34
9.73
Fever prior to implantation
2
6391
OR
5.39 [1.18, 24.61]
0.03
0.2
40.47
Oral anticoagulants
6
7200
OR
1.64 [0.99, 2.71]
0.05
0.06
52.85
Antiplatelet therapy
3
6694
OR
1.44 [0.82, 2.54]
0.21
0.36
1.87
Corticosteroid use
7
2105
OR
5.28 [2.29, 12.18]
0.0001
0.38
6.65
Immunosuppressive drug usec 2
291
OR
1.85 [0.63, 5.46]
0.27
0.49
0
Permanent CVC
3
1181
OR
5.74 [0.94, 34.93]
0.06
0.15
47.18
History of device infection
4
463
OR
7.84 [1.94, 31.60]
0.004
0.17
40.10
Antibiotic prophylaxis
15
13727
OR
0.37 [0.21, 0.64]
0.0004
0.01
51.02
Device replacement/
17
17539
OR
2.00 [1.39, 2.89]
0.0002
0.01
50.02
Generator change
16
11063
OR
1.74 [1.15, 2.63]
0.009
0.02
46.83
Lead dislodgement/
4
1659
OR
8.71 [3.86, 19.64]
0.0000002 0.60
Hematoma
8
8575
OR
9.78 [3.70, 25.84]
0.000004
0.003 68.12
Temporary pacing
7
8843
OR
2.05 [1.02, 4.12]
0.04
0.05
Procedure duration
4
1961
WMD
9.92 [-8.94, 28.78]
0.30
0.001 81.58
Inexperienced operator d
2
1715
OR
2.85 [1.23, 6.58]
0.01
0.47
0
ICD device
7
9469
OR
0.93 [0.65, 1.33]
0.69
0.70
0
CRT device
4
8629
OR
3.79 [0.71, 20.30] 0.12
0.007 75.19
Dual-chamber device
10
11300
OR
1.70 [1.11, 2.59]
0.01
0.1
39.39
≥2 leads
4
468
OR
2.03 [0.94, 4.37]
0.07
0.06
60.56
Abdominal generator pocket
2
291
OR
2.18 [0.93, 5.10]
0.07
0.96
0
Presence of epicardial leads
3
623
OR
8.09 [3.46, 18.92] 0.000001
0.98
0
Presence of abandoned leads
2
291
OR
1.82 [0.86, 3.83]
0.51
0
Procedure-related factors
revision/upgrade
0
repositioning
52.28
Device-related factors
0.12
WMD weighted mean difference, OR odds ratio, BMI body mass index, ESRD end-stage renal disease, CAD
coronary artery disease, CABG coronary artery bypass grafting, CHF congestive heart failure, COPD chronic
obstructive pulmonary disease, CVC central venous catheter, ICD implantable cardioverter defibrillator, CRT
cardiac resynchronization therapy.
a
Glomerular filtration rate (GFR) <60 ml/min or creatinine clearance (CrCL) <60 ml/min
GFR≤ 15 ml/min or hemodialysis or peritoneal dialysis
c
Immunosuppressive drugs other than corticosteroids
d
<100 previous procedures
b
Supplementary Table 5. Sensitivity analysis including only prospective studies.
Factor
Studies Totals Statistical Pooled estimate
P value Heterogeneity
Method
P
I2
Host-related factors
Age
5
3852
WMD
-2.04 [-5.19, 1.10]
0.20
0.70
0
Male gender
8
14965
OR
1 [0.70, 1.42]
0.98
0.36
8.87
Diabetes mellitus
7
9815
OR
1.88 [1.19, 2.98]
0.007
0.74
0
NYHA class ≥ 2
2
2393
OR
2.77 [1.26, 6.05]
0.01
0.43
0
Ejection fraction
2
952
WMD
-0.83 [-4.06, 2.40]
0.62
0.38
0
COPD
2
2393
OR
2.30 [0.97, 5.48]
0.06
0.36
0
Skin disorders
2
6519
OR
2.60 [0.88, 7.70]
0.08
0.63
0
Fever prior to implantation
2
6580
OR
5.34 [1.002, 28.43] 0.05
0.20
38.05
Oral anticoagulants
3
7271
OR
1.18 [0.44, 3.11]
0.75
0.12
53.50
Antiplatelet therapy
2
6622
OR
1.19 [0.62, 2.28]
0.61
0.38
0
Corticosteroid use
3
1349
OR
2.10 [0.47, 9.32]
0.33
0.91
0
Antibiotic prophylaxis
11
10864
OR
0.29 [0.13, 0.63]
0.002
0.001
66.35
Device replacement/
8
8793
OR
0.95 [0.49, 1.87]
0.89
0.07
47.13
Procedure-related factors
revision/upgrade
Generator change
6
2139
OR
0.91 [0.37, 2.22]
0.83
0.06
52.26
Lead dislodgement/
4
1659
OR
7.03 [2.49, 19.85]
0.0002
0.22
32.17
Hematoma
6
9715
OR
9.33 [2.84, 30.69]
0.0002
<0.001 78.12
Temporary pacing
4
8683
OR
3.29 [1.87, 5.80]
0.00004 0.43
Procedure duration
6
4508
WMD
13.04 [-0.64, 26.73] 0.06
0.02
63.41
Inexperienced operator a
2
1715
OR
2.85 [1.23, 6.58]
0.01
0.47
0
ICD device
4
8676
OR
1.01 [0.5, 2.03]
0.98
0.68
0
CRT device
4
9016
OR
1.82 [0.86, 3.86]
0.12
0.56
0
Dual-chamber device
7
12102
OR
1.28 [0.73, 2.25]
0.38
0.15
37.19
Abdominal generator pocket
2
2268
OR
5.03 [1.96, 12.91]
0.0008
0.31
3.75
repositioning
0
Device-related factors
WMD weighted mean difference, OR odds ratio, NYHA New York Heart Association, COPD chronic obstructive pulmonary
disease, ICD implantable cardioverter defibrillator, CRT cardiac resynchronization therapy.
a
<100 previous procedures
Supplementary Table 6. Assessment of publication bias for factors examined by at least 5
studies.
Funnel plot
Egger’s test
Bias?
P value
Age
No
Male gender
Risk factor
Trim and Fill method
Studies
OR [95% CI],
trimmed (N)
before/after trim and fill
0.19
0
NA
Yes
0.12
4
1.12 [0.89, 1.41] / 1.07 [0.86, 1.35]
Diabetes
No
0.5
0
NA
Renal insufficiency
Yes
0.27
1
3.02 [1.38, 6.64] / 2.64 [1.25, 5.60]
ESRD
No
0.63
0
NA
Atrial fibrillation
No
0.51
0
NA
CAD
No
0.10
0
NA
CHF
No
0.94
0
NA
COPD
Yes
0.45
3
2.95 [1.78, 4.90] / 2.38 [1.56, 3.63]
Malignancy
Yes
0.85
1
2.23 [1.26, 3.95] / 2.05 [1.18, 3.57]
Oral anticoagulants
No
0.14
0
NA
Corticosteroid use
No
0.54
0
NA
Antibiotic
Yes
0.004
5
0.32 [0.18, 0.55] / 0.52 [0.28, 0.96]
No
0.28
0
NA
No
0.26
0
NA
prophylaxis
Device replacement/
revision/upgrade
Generator change
Lead dislodgement/
No
0.54
0
NA
Hematoma
No
0.64
0
NA
Temporary pacing
No
0.59
0
NA
Procedure duration
No
0.90
0
NA
ICD device
No
0.65
0
NA
CRT
No
0.34
0
NA
Dual-chamber device
Yes
0.19
5
1.45 [1.02, 2.05] / 1.07 [0.74, 1.56]
≥2 leads
Yes
0.42
3
2.02 [1.1, 3.69] / 1.17 [0.58, 2.37]
Abdominal generator
Yes
0.41
1
4.01 [2.48, 6.49] / 3.65 [2.31, 5.77]
repositioning
pocket
OR odds ratio, 95% CI 95% confidence interval, NA not applicable, ESRD end-stage renal disease, CAD
coronary artery disease, CHF congestive heart failure, COPD congestive obstructive pulmonary disease, ICD
implantable cardioverter-defibrillator, CRT cardiac resynchronization therapy.
Supplementary Table 7. Assessment of the methodological quality of randomized studies
that examined the effectiveness of antibiotic prophylaxis.
Study ID
Random sequence
Allocation
Blinding
Incomplete outcome
generation
concealment
Muers 1981
High risk
High risk
No
Low risk
Ramsdale 1984
Low risk
Unclear
No
Unclear
Bluhm 1984
Unclear
Unclear
No
Low risk
Bluhm 1986
Unclear
Unclear
Double-blind
Low risk
Glieca 1987
Unclear
Unclear
No
Unclear
Lüninghake 1993
Unclear
Unclear
No
Unclear
Mounsey 1994
Unclear
Unclear
No
Low risk
Oliveira 2009
Unclear
Unclear
Double-blind
Low risk
data
SUPPLEMENTARY FIGURE LEGENDS
Supplementary Figure 1. Microbiology of CIED infection.