Supplementary Appendix

This appendix has been provided by the authors to give readers additional information about their work.
Supplement to: Bennett-Guerrero E, Pappas TN, Koltun WA, et al. Gentamicincollagen sponge for infection
prophylaxis in colorectal surgery. N Engl J Med 2010;363:1038-49. DOI: 10.1056/NEJMoa1000837.

Online Supplement Table 1 Microbial Pathogens Isolated from Surgical Site

Infections in the Per Protocol Population
GentamicinCollagen
Sponge Arm

Control Arm

44

28

Anaerobes

1 (2.3%)

2 (7.1%)

0.556

Citrobacter species

1 (2.3%)

1.000

Coagulase-neg staphylococci

1 (3.6%)

0.389

Enterobacter cloacae

3 (10.7%)

0.055

Enterococci

3 (6.8%)

2 (7.1%)

1.000

Enterococcus avium

1 (2.3%)

1.000

Enterococcus faecalis

8 (18.2%)

2 (7.1%)

0.297

Enterococcus faecium

3 (6.8%)

1 (3.6%)

1.000

11 (25.0%)

5 (17.9%)

0.477

1 (3.6%)

0.389

Klebsiella oxytoca

1 (2.3%)

1 (3.6%)

1.000

Klebsiella pneumoniae

2 (4.5%)

2 (7.1%)

0.640

Klebsiella spp

1 (2.3%)

1.000

Methicillin-resistant SA

4 (9.1%)

5 (17.9%)

0.297

Methicillin-sensitive SA

9 (20.5%)

5 (17.9%)

0.786

Morganella morganii

2 (4.5%)

1 (3.6%)

1.000

Proteus mirabilis

5 (11.4%)

1 (3.6%)

0.394

Pseudomonas aeruginosa

4 (9.1%)

3 (10.7%)

1.000

Staphylococcus epidermidis

8 (18.2%)

4 (14.3%)

0.755

1 (3.6%)

0.389

Staphylococcus warneri

1 (2.3%)

1.000

Streptococcus agalactiae

1 (2.3%)

1 (3.6%)

1.000

Number of patients

Escherichia coli
Group B species streptococcus

Staphylococcus haemolyticus

P-value

SA = Staphylococcus aureus

Online Supplement Table 2 Sensitivity of Microbiological Isolates to Gentamicin

Gentamicin-Collagen
Sponge Arm
Sensitive Resistant
Number of

to

to

Control Arm
Sensitive Resistant
Number of

to

to

Microbial Pathogens

isolates

Citrobacter species

Enterobacter cloacae

Enterococcus avium

Enterococcus faecalis

Enterococcus faecium

Escherichia coli

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii

Proteus mirabilis

Pseudomonas aeruginosa

Staphylococcus aureus

Staphylococcus epidermidis

Staphylococcus haemolyticus

Staphylococcus warneri

Streptococcus agalactiae

Gentamicin Gentamicin

isolates

Gentamicin Gentamicin

Online Supplement Table 3 - Adverse Events

Gentamicin

Control

Collagen Sponge
n=296

n=306

Number of all adverse events

2840

2645

Number of non-serious adverse events

2641

2488

199/2840 (7.0%)

157/2645 (5.9%)

114 (38.5%)

101 (33.0%)

Small intestinal obstruction

8 (2.7%)

10 (3.3%)

Abdominal wound dehiscence

7 (2.4%)

3 (1.0%)

Anastomotic leak

8 (2.7%)

4 (1.3%)

Postoperative ileus

30 (10.1%)

19 (6.2%)

Dehydration

14 (4.7%)

9 (2.9%)

Acute renal failure

3 (1.0%)

3 (1.0%)

Number of serious adverse events

Number of patients with at least 1 serious adverse event

Safety population (n=602) includes as treated so 4 subjects randomized to Sponge but not receiving
any sponges are part of control group for safety analyses.
Serious adverse events occurring in at least 1% of subjects are shown.
Data shown as number (percentage).

Online Supplement Table 4 Structured Wound Healing Questionnaire

Question

Sponge

Control

14 (4.9)

10(3.5)

Afraid to make movement for fear of disrupting incision?

29 (10.1)

36 (12.5)

Current limitation to body movement related to incision?

50 (17.4)

57 (19.8)

More than 1 inch of redness around incision?

30 (10.5)

23 (8.0)

7 (2.4)

7 (2.4)

Drainage from incision?

116 (40.3)

83 (28.7)

Abdominal/belly incision area still tender to touch?

102 (35.4)

95 (33.0)

14 (4.9)

10 (3.5)

3 (1.0)

2 (0.7)

Afraid to make movement for fear of disrupting incision?

9 (3.1)

9 (3.1)

Current limitation to body movement related to incision?

19 (6.6)

17 (5.9)

More than 1 inch of redness around incision?

9 (3.1)

10 (3.4)

Bruising around incision?

1 (0.3)

1 (0.3)

Drainage from incision?

48 (16.6)

34 (11.8)

Abdominal/belly incision area still tender to touch?

51 (17.6)

45 (15.5)

6 (2.1)

3 (1.0)

30 Day Questionnaire
Bulging/swelling around incision concerning enough to call
surgeon?

Bruising around incision?

Constant pain in abdominal/belly incision?

60 Day Questionnaire
Bulging/swelling around incision concerning enough to call
surgeon?

Constant pain in abdominal/belly incision?

Number (percentage) are shown.

Online Supplement Figure 1

Serum Gentamicin Levels

Shows serum gentamicin levels (mcg/ml) prior to and 2, 6, 12, 24, and 48 hours after insertion
of 2 Gentamicin-Collagen Sponges in 48 subjects
5.0

4.5

4.0

Gentamicin Concentration mcg/mL

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0
Base
line

2
Hrs

6
Hrs

12
Hrs

24
Hrs

48
Hrs

Time Points

Online Supplement Appendix 1

Detailed Inclusion Criteria: 1) Male or female patients 18 years old, 2) Scheduled to undergo one of
the following 13 colorectal surgeries:

left hemicolectomy, transverse colectomy, segmental/sleeve left

colon resection, total abdominal colectomy with ileorectal anastomosis, total abdominal colectomy with
ileostomy, total abdominal proctocolectomy (portion of specimen to be extracted via laparotomy), low
anterior resection, sigmoid resection, non-emergent hartmann's procedure, colotomy with polypectomy
distal to hepatic flexure, colostomy takedown through laparotomy (not peristomal) incision, ileo-pouch
anal anastomosis, abdominal perineal resection of the rectum. Laparascopic assisted procedures were
allowed as long as they involved use of a laparotomy incision of 7 cm in length, e.g. hand assisted
procedure or extraction of the specimen. Right hemicolectomy was not allowed.
Detailed Exclusion Criteria: 1) known history of hypersensitivity to gentamicin or bovine collagen, 2)
emergency surgery, 3) Significant concomitant surgical procedure. The following concomitant
procedures were allowed: appendectomy, cholecystectomy, oophorectomy, liver biopsy/wedge resection,
4) Laparoscopic, laparoscopic-assisted, or other minimally invasive surgical approach involving a
laparotomy incision less than 7 cm, 5) Prior laparotomy within the last 60 days, 6) Planned second
laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 60 days of
this planned first procedure, 7) Preoperative sepsis, severe sepsis, or septic shock, 8) Abdominal wall
infection/surgical site infection from previous laparotomy/laparoscopy or for any reason, 9) Antibiotic
therapy within the 1 week prior to the date of surgery, 10) Preoperative evaluation suggests intraabdominal process that might preclude full closure of the skin, 11) Ongoing treatment (e.g.
chemotherapy, radiation) for non-colorectal cancer, 12) Recent history of significant drug or alcohol
abuse, 13) Prothrombin time (PT) > 1.5 times upper limit of normal, 14) Pregnant or lactating, 15)
Postsurgical life expectancy 60 days; 16) Refusal to accept medically indicated blood products, 17)
Previous participation in this or any other active Innocoll Gentamicin-Collagen Sponge study, 18)
Participation within 30 days before the start of this study in any experimental drug or device study, or
currently participating in a study in which the administration of investigational drug or device within 60
days is anticipated, 19) Not technically possible to insert 2 sponges above the fascia in the patient (e.g.
very thin patient with small incision), 20) Patients with anterior abdominal wall mesh that is not planned
to be completely removed during the planned procedure, 21) Presence of prosthetic cardiac valve that
might require prophylactic antibiotics other than those called for by the protocol.