Supplementary Appendix

Transcription

1 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. Gentamicin collagen sponge for infection prophylaxis in colorectal surgery. N Engl J Med 2010;363: DOI: /NEJMoa

2 Online Supplement Table 1 - Microbial Pathogens Isolated from Surgical Site Infections in the Per Protocol Population Gentamicin- Collagen Sponge Arm Control Arm P-value Number of patients Anaerobes 1 (2.3%) 2 (7.1%) Citrobacter species 1 (2.3%) Coagulase-neg staphylococci 0 1 (3.6%) Enterobacter cloacae 0 3 (10.7%) Enterococci 3 (6.8%) 2 (7.1%) Enterococcus avium 1 (2.3%) Enterococcus faecalis 8 (18.2%) 2 (7.1%) Enterococcus faecium 3 (6.8%) 1 (3.6%) Escherichia coli 11 (25.0%) 5 (17.9%) Group B species streptococcus 0 1 (3.6%) Klebsiella oxytoca 1 (2.3%) 1 (3.6%) Klebsiella pneumoniae 2 (4.5%) 2 (7.1%) Klebsiella spp 1 (2.3%) Methicillin-resistant SA 4 (9.1%) 5 (17.9%) Methicillin-sensitive SA 9 (20.5%) 5 (17.9%) Morganella morganii 2 (4.5%) 1 (3.6%) Proteus mirabilis 5 (11.4%) 1 (3.6%) Pseudomonas aeruginosa 4 (9.1%) 3 (10.7%) Staphylococcus epidermidis 8 (18.2%) 4 (14.3%) Staphylococcus haemolyticus 0 1 (3.6%) Staphylococcus warneri 1 (2.3%) Streptococcus agalactiae 1 (2.3%) 1 (3.6%) SA = Staphylococcus aureus 1

3 Online Supplement Table 2 Sensitivity of Microbiological Isolates to Gentamicin Microbial Pathogens Number of isolates Gentamicin-Collagen Sponge Arm Sensitive Resistant to to Gentamicin Gentamicin Number of isolates Control Arm Sensitive Resistant to to Gentamicin Gentamicin 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

4 Online Supplement Table 3 - Adverse Events Gentamicin Collagen Sponge n=296 Control n=306 Number of all adverse events Number of non-serious adverse events Number of serious adverse events 199/2840 (7.0%) 157/2645 (5.9%) Number of patients with at least 1 serious adverse event 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%) 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). 3

5 Online Supplement Table 4 Structured Wound Healing Questionnaire Question Sponge Control 30 Day Questionnaire Bulging/swelling around incision concerning enough to call surgeon? 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) Bruising around incision? 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) Constant pain in abdominal/belly incision? 14 (4.9) 10 (3.5) 60 Day Questionnaire Bulging/swelling around incision concerning enough to call 3 (1.0) 2 (0.7) surgeon? 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) Constant pain in abdominal/belly incision? 6 (2.1) 3 (1.0) Number (percentage) are shown. 4

6 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 Gentamicin Concentration mcg/ml Base line Time Points 5

7 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. 6