Prevention of Surgical Site Infection by Gentamicin-Impregnated Collagen Sponge (Collashield® Double Action) in Patients Who Underwent Abdominal Surgery CURRENT

Background: The aim of this study was to evaluate the efficacy of the gentamicin-impregnated collagen sponge (GCS) in preventing SSI after abdominal surgeries. Methods: We conducted a retrospective study to evaluate the effect of GCS in preventing postoperative surgical site infection (SSI) in patients who underwent abdominal surgeries. 194 patients (111 male and 83 female; mean age, 62 years; range, 20-96 years) who underwent abdominal surgery between January 2017 and December 2018 in Chuncheon Sacred Heart Hospital were included in this study. The primary endpoint was the development of any SSI within 1 month postoperatively. Results: Of 194 patients studied, 30(20.1%, control group) and 6(13.3%, sponge group) in each group developed a SSI. However, subgroup analysis in patients with contaminated and dirty wound showed that SSI was occurred more frequently in the control group (15 of 36 [41.7%]) than in the sponge group (3 of 22 [13.6%]) (P = 0.04). Our data suggest that postoperative SSI can be reduced by using GCS in in the group of patients with contaminated and dirty wound classes. Conclusions: The SSI rate after abdominal surgeries was reduced in the group of patients with contaminated and dirty wound classes, by using GCS. We should consider to use GCS in patients with these type of wounds.


Background
Surgical site infection (SSI) is a common complication after abdominal surgery. SSI rates have been reported up to 20% in several studies [1][2][3]. Prophylactic methods include systemic antibiotic use, control of the operating room environment, and improvements of surgical techniques [4][5][6].
Appropriate wound management is important in surgical patients because wound problems are associated with profound morbidity, impaired quality of life and significant economic costs. Also SSI is associated with length of hospital stay and increased hospital costs. As a result, the prevention of SSI is important to get a great benefit in terms of individual health and economic issues. Therefore, surgeon should actively involve in wound care to minimize the SSI. Systematic care, including correction of medical co-morbidities, improvement of nutritional status, or surgical debridement of infected wound should be performed in accordance with proper use of antimicrobial agents to facilitate optimal wound healing [7][8][9].
A gentamicin-impregnated collagen sponge (GCS) has been developed to prevent SSI. This reabsorbable material is designed to be implanted before closure of the wound in many types of surgeries including abdominal, dental, cardiac, breast or orthopedic surgeries [2,3,5,[10][11][12][13][14]. The GCS is composed of highly purified type I collagen obtained from bovine tendon, which acts as a vehicle for the antimicrobial gentamicin. So it maintains high local concentrations of gentamicin, so that minimize postoperative bacterial growth, preventing SSI.
Some studies have demonstrated the effectiveness of the GCS in abdominal surgery patients.
Rutten et al. [2] concluded that GCS was effective to reduce postoperative wound infection rates to levels lower than those currently achieved with systemic antibiotics alone. However, one metaanalysis by Nelson et al. [1] showed conflicting results probably due to varying methodologies, study populations, small sample size, and lack of randomized trial. Furthermore, most of studies were limited in colorectal surgery.
Therefore, the objective of this study was to determine whether GCS reduces SSI after abdominal surgeries including gastrointestinal, hepato-biliary, pancreatic and biliary surgeries. We compared postoperative SSI rates in 194 patients who underwent abdominal surgery with (Sponge group, n = 49) or without (Control group, n = 145) the GCS, retrospectively.

Methods Patients
Between January 2017 and December 2018, 194 patients who underwent abdominal surgery with (Sponge group, n = 49) or without (Control group, n = 145) the GCS, were selected respectively. All of the 194 patients enrolled in the present study received a complete evaluation included physical examination, blood tests, chest and electrocardiography prior to surgery. Patients with either elective or emergency operation were included. Patients who underwent laparoscopic surgeries or leaving the wound open during first few days after surgery (delayed wound closure), were excluded. Types of surgical wound were classified by the American College of Surgeons considering the following categories: (1) clean wounds; (2) contaminated clean wounds; (3) contaminated wounds; and 94) dirty wounds [15,16].
Approval for this study was obtained from our Institutional Review Broad.
Operative procedure During the study period, Collashield® Double Action (BNC KOREA, Taegu, Korea) was to be used randomly according to surgeon's preference. Each sponge (5 by 5 cm) contained 2.8 mg/cm 2 of bovine collagen and 2.0 mg/cm 2 of gentamicin sulfate. We inserted one sponge, which was cut into strips according to the length of wound, anteriorly to the fascia immediately before closure of the wound.

Diagnosis of SSI
Patients with SSI usually present the signs and symptoms such as wound pain, redness or swelling of the wound, or dehiscence with/without drainage of pus. If there were clear evidences of SSI, we performed wound exploration and swab culture for diagnosis. If the patients showed no specific signs or symptoms, we considered computed tomography (CT) for accurate diagnosis for deep or organ space SSI.

End points
The primary endpoint was SSI including abnormal fluid collection or abscess formation in subcutaneous space or deeper spaces within 1 month after surgery. We assessed the presence of SSI by reviewing electronic medical records of hospital data and outpatient department follow-up.

Statistical analysis
Continuous data were expressed as the mean ± standard deviation. Student's t test and Fisher's exact probability test were used for the analysis each of continuous and categorical data. Data analysis was performed using SPSS software (Version 12.0; SPSS, Chicago, Il1). P Values < 0.05 were considered statistically significant.

Results
Baseline characteristics and overall SSI rates were summarized in Table 1. There were no significant differences between two groups in terms of various factors except for type of wound. Sponge group was consisted relatively large proportion of contaminated and dirty wound rather than control group, representing surgeons intended to use the GCS more frequently in patients with contaminated and dirty wound. However, the overall SSI rates were not different significantly between two groups. Of 194 patients studied, 30(20.1%, control group) and 6(13.3%, sponge group) in each group developed SSIs. In univariate analysis using Fisher's exact probability test showed that only the type of wound was associated with SSI development significantly (P = 0.025). SSI was occurred more frequently in patients with co-morbidities (hypertension, DM, COPD, cardiac disease, renal disease or liver cirrhosis) but, the results were not reached to the statistical significance. Also the use of GCS was not associated with SSI development significantly (P = 0.384) (     Discussions SSI is associated with quality of life, increased lengths of hospital stay, so that significant benefits is expected from the prevention of SSI. The GCS was developed to reduce SSI by providing high local gentamicin concentrations but no the high systemic concentrations associated with nephrotoxicity [17]. The GCS was first approved in Germany in 1985 and is currently used in over 60 countries [14].
In view of these results, our department of surgery started to use GCS in early 2017.  [15].
The organisms most frequently found in SSI are the gram-negative anaerobes such as Escherichia coli, Klebsiella sp., Proteus mb and Pseudomonas aeruginosa, among others; therefore aminoglycosides should be included in the treatment regimens for the SSI [16,22]. For gentamicin, a positive influence on anastomotic healing and the quality of collagen formation could be shown [23], whereas Bang et al. [24] reported GCS hampering epithelialization and neovascularization in a mouse model. Vaneerdeweg et al. [24] set up a rat model in which nearly all rats in the collagen group developed anastomotic breakdowns. However, there were no cases of wound disruption or incisional hernia in both groups during the study periods.
In our results, the length of hospital stay was not different between two group (18.43 ± 20.89 versus 19.91 ± 14.47; P = 0.665). But Sponge group was consisted relatively large proportion of contaminated and dirty wound rather than control group that means sponge group is consisted with more severe patients compared to control group.
It has been well known that immediate closure of contaminated or dirty abdominal wounds at the time of surgery increases the risk of SSI. The most frequent method for preventing SSI consists in leaving the wound open and closing it within 3 to 5 days. However this make the patients feel severe pain during the wound dressing until wound is closed and it is associated with increased length of hospital stay. Therefore, the GCS is more comfortable and effective rather than delayed wound closure.
This study has several limits. First one is that this is retrospective study. Also the use of GCS was determined by surgeon's preferences. Finally, we used only 1 size of GCS in this study, however, previous study demonstrated that larger size of GCS is more effective related to the size of wound [21]. Randomized controlled trial using several sizes of GCS is needed in the future.

Conclusions
In conclusion, our results demonstrate that the SSI rate after abdominal surgeries was reduced in the group of patients with contaminated and dirty wound classes, by using GCS. We should consider to use GCS in patients with these type of wounds.