Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver

Surgical-site infection (SSI) occurs in 300,000 to 500,000 patients who undergo surgery in the US each year. For surgical patients, SSI are the most common hospital-acquired infection. In clean-contaminated and contaminated surgery, such as elective major colorectal surgery, there has been wide discrepancy in the reported incidence of incisional SSI, ranging from 3% to 30% [1, 2], reflecting differences in diagnostic criteria and follow-up applied. SSI is associated with significant attributable morbidity and mortality, prolonged hospital length of stay, and a high cost to the patient and the institution. Several studies have suggested a doubling of the mortality rate, with an annual cost of $1.8 billion to the US health care system and £1 billion to the National Health Service in England [3, 4]. Because the patient’s skin is a major source of pathogens, it is conceivable that improving skin antisepsis would decrease SSIs; a large randomized trial has shown that preoperative cleansing of the patient’s skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery, including colorectal procedures [5].

Ionic silver (Ag+), which is the oxidized active state of silver, has received renewed interest and research for use as a prophylactic antimicrobial agent in wound dressings due to its broad spectrum antibacterial range, including aerobic, anaerobic, Gram-negative and Gram-positive bacteria, as well as yeast and fungi [6‐8]. Aquacel® Ag Hydrofiber dressing (ConvaTec, Princeton, NJ, USA) is a moisture retention dressing that consists of soft non-woven sodium carboxymethylcellulose fibers combined with 1.2% ionic silver, which is distributed throughout the dressing material. The concept of Aquacel® Ag Hydrofiber dressing is to retain the hydrofiber’s physical properties with the additional benefits of ionic silver, which is slowly released into the wound, creating a moist antimicrobial environment. Multiple clinical studies have been performed to assess its effectiveness for the treatment of a variety of wounds, managed in acute and chronic settings. Nevertheless, a recent Cochrane systematic review failed to find an advantage for silver-containing wound dressings after analyzing 26 randomized controlled trials that compared silver-containing wound dressings and topical agents with silver-containing and non-silver-containing comparators on uninfected wounds. The authors of the review concluded that there is insufficient evidence to establish whether silver-containing dressings or topical agents promote wound healing or prevent wound infection [9]. No published randomized studies have previously examined the effect of silver-containing wound dressing on the incidence of SSI. The average baseline rate of SSI after colorectal cancer elective surgery at the European Institute of Oncology was 23% with common postoperative dressing; a pilot prospective non-randomized study of 100 patients showed a reduction of this rate to 4% by substituting the Aquacel® Ag Hydrofiber dressing for the common dressing [10]. We decided to test this preliminary finding in a prospective, randomized, double-blind trial against a common dressing as control, having the main objective to compare the efficacy of Aquacel® Ag Hydrofiber dressing with that of a common postoperative one for preventing SSIs in colorectal cancer elective surgery.

Randomized studies have compared the efficacy of different types [11‐13] or doses [14, 15] of systemic antibiotics for preventing SSIs; influence of different preoperative skin antisepsis agents was also investigated [5]. To our knowledge, this is the first randomized controlled trial addressing the efficacy of an ionic-silver-delivering antimicrobial dressing in lowering the SSI rate of patients having colorectal cancer elective open surgery.

Animal models have been used to study the performance and cytotoxicity of Aquacel Ag Hydrofiber dressing in vivo. In a full-thickness infected mouse wound model, Yates and colleagues showed that Aquacel Ag Hydrofiber lowered wound bacteria loads, obtained superior wound tensile strength, and accelerated epithelialization compared with untreated infected wounds [16]. Multiple clinical studies have been performed to assess Aquacel Ag Hydrofiber effectiveness for the treatment of a variety of acute and chronic wounds. Caruso et al. carried out a stratified, randomized prospective, though un-blinded study, comparing Aquacel Ag Hydrofiber and silver sulfadiazine in the management of partial thickness burns [17, 18]. Aquacel Ag Hydrofiber was associated with significantly less pain and anxiety during dressing changes, significantly fewer procedural and opiate medications, significantly less burning and stinging during wear, and greater cost-effectiveness than silver sulfadiazine.

Other clinical studies on partial thickness burns treatment showed good wound healing, reduced pain, fewer dressing changes and better cost-effectiveness with Aquacel Ag Hydrofiber compared to standard treatment [19‐21]. In patients with acute split-thickness skin-graft donor sites and acute traumatic wounds [22, 23], Aquacel Ag Hydrofiber showed superior re-epithelialization rates and was associated with less pain on dressing removal in comparison with standard treatment. Jurczak and colleagues of the Aquacel Ag Surgical/Trauma Wound Study Group carried out a prospective, randomized clinical trial comparing pain, comfort, exudate management, wound healing and safety with Hydrofiber dressing with ionic silver (Aquacel Ag Hydrofiber dressing) and with povidone-iodine gauze for the treatment of open surgical and traumatic wounds [22]. At final evaluation, Aquacel Ag Hydrofiber dressing was significantly better than povidone-iodine gauze for overall ability to manage pain, overall comfort, wound trauma on dressing removal, exudate handling and ease of use. Rates of complete healing at study completion were 23% for Aquacel Ag Hydrofiber dressing and 9% for povidone-iodine gauze (P-value was non-significant).

There are several limitations of our study that deserve some mentions. First, results of this randomized trial are conflicting with those initially reported by our group in a Congress abstract [10], summarizing the data of a pilot study carried out in 100 patients consecutively receiving Aquacel Ag Hydrofiber dressing after elective colorectal cancer surgery. In that report, we observed an overall SSI rate of 4%, which is much less than the 15.5% we detected in this randomized trial. However, limitations of observational non-randomized studies are well known and emphasized, especially uncertainty about whether all confounders had been controlled for. Double-blinding was accurately provided in this randomized trial, and we can reasonably argue that initial results should be interpreted cautiously, particularly given the absence of blinding in that initial experience. Moreover, the usage of the secondary dressing to blind the study might have affected the overall performance of the antimicrobial dressing.

Second, the overall rates of SSI of 17.9% in this study are higher than those reported in some previous studies [24, 25]; nevertheless, they are similar to the pre-study rates at the participating hospitals and those reported in other studies [26] and are lower than the rates reported in trials that used the CDC definition of infection and had adequate follow-up [2, 12, 13], as we did in this trial. In this study we universally enforced standard of care preventive measures (for example, administering systemic prophylactic antibiotics within the 30 minutes before the first incision was made and, if needed, clipping hair immediately before surgery) [27, 28]. However, we did not use chlorhexidine-alcohol as the skin preparation agent; although the povidone-iodine we used possesses broad spectrum antimicrobial activity [27], a recent randomized controlled trial demonstrated that preoperative cleansing of the patient’s skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing SSI after clean-contaminated surgery [5]. This is probably related to its more rapid action, persistent activity despite exposure to bodily fluids, and residual effect [29].

Finally, the sample size of this trial could appear smaller than required, and the study globally underpowered to detect a significant difference in infections rates, even though the sample size was accurately determined on the basis of a pilot non-randomized prospective study. We were not able to enroll more patients in the timeframe we assigned to the study, as minimally invasive surgery (a factor excluding eligibility in this trial) has come to be more and more applied to surgical treatment of colorectal cancer. Superficial SSIs have been significantly reduced by the application of minimally invasive techniques [30]. Precise robotic movements and fine manipulation of tissues in a close and fixed operating field make especially rectal cancer surgery an important application of minimally invasive robotic surgery, and in fact robot-assisted low-anterior resection was reported by ours and other groups as a technically feasible and oncologically safe procedure for treatment of rectal cancer [31, 32].

In conclusion, Aquacel Ag Hydrofiber dressing showed a reduction in the overall SSI rate compared with a common postoperative dressing in elective colorectal open major procedures, although the registered infections rates were not statistically significant. Moreover, there were no significant differences between the two study groups in the incidence of superficial and deep infections of surgical wounds and, as expected, there was no difference in organ-space infection rate either. The finding that rectal cancer surgery is more prone to SSI compared with colon surgery confirms previous reports in the literature. No adverse events related to the study were detected. More trials are needed to definitely address this topic, testing new products developed specifically for surgical incisions, such as Aquacel Ag Surgical cover dressing (Hydrofiber Technology combined with skin-friendly hydrocolloid substrate), which provides a waterproof and viral and bacterial barrier that allows for flexibility and extensibility during body movement.