Gentamicin sponge may not prevent SSIs during colorectal surgery

Bennett-Guerrero E. NEJM. 2010. doi:10.1056/NEJMoa1000837.

A gentamicin-collagen sponge may have resulted in an increased rate — not a decreased rate, as was expected — of surgical site infections following colorectal surgery, according to study findings.

The studied sponge is an implantable topical antibiotic agent that has been approved for use in 54 countries. It has been used to treat more than 1 million patients and using the sponge was intended to enhance routine antibiotic prophylaxis regimens. The sponge contains 280 mg of collagen and 130 mg of gentamicin.

The current phase 3 trial involved 602 patients who had received open or laparoscopically-assisted colorectal surgery at 39 sites in the United States. Patients were randomly assigned to undergo either the insertion of two gentamicin–collagen sponges above the fascia at the time of surgical closure, which the researchers called the sponge group, or no intervention, which was the control group.

Standard care, including prophylactic systemic antibiotics, was administered to all patients. A clinical events classification committee that was unaware of study group assignments assessed patients for surgical site infection within 60 days after surgery, which the researchers defined as the primary endpoint.

Regarding secondary endpoints, surgical site infection occurred in 30.0% of sponge group patients and 20.9% of control group patients (P=0.01), according to results. Findings also indicated that superficial surgical-site infection was observed in 20.3% of patients in the sponge group and 13.6% of patients in the control group (P =0.03). Deep surgical-site infections occurred in 8.3% of sponge group patients and 6.0% of controls (P =0.26).

Patients in the sponge group visited an emergency room or surgeon’s office due to a wound-related sign or symptom at a rate of 19.7%, compared with 11.0% of controls (P=0.004). Rehospitalization for surgical-site infection occurred in 7.0% of sponge patients and 4.3% of controls (P=0.15).

Adverse event profiles were similar in the two groups.

“Our large, multicenter trial shows that the gentamicin–collagen sponge is not effective at preventing surgical-site infection in patients who undergo colorectal surgery,” the researchers wrote. “Paradoxically, it appears to result in significantly more surgical-site infections.”

PERSPECTIVE

Post-operative infection rates following colorectal surgery are normally quite high - in the range of 10%-25% - and efforts to decrease these rates are certainly appropriate. The prophylactic use of gentamicin-impregnated collagen sponges following colorectal surgery is approved by regulatory authorities in Europe, and evidently widely practiced. Indeed, there are several published studies that support such use, and show decreases of 50% or more in post-operative infections using such sponges.

This study was extremely carefully planned and executed in order to obtain FDA approval in the United States. It is rare to find a negative study published in the NEJM, but this was more than just a negative study; the data indicate that the intervention - gentamicin-impregnated collagen sponges - was downright harmful. It will be interesting to observe what the European regulatory authorities will do with this study, and how practice might evolve in response.

One can only speculate at this point on the mechanism at work in producing this deleterious effect. One possibility is that the sponge, after sufficient gentamicin has eluted, may simply be acting as a foreign body; there may be others as well.

Thinking more broadly, one might wonder what such a carefully done study of gentamicin-impregnated beads used in orthopedic surgery might show. Such use is sometimes prophylactic, but probably more often therapeutic in nature. It will never happen; the numbers simply are not there - and that is good!

– Theodore C. Eickhoff, MD
Infectious Disease News Chief Medical Editor