Introduction
Philip S. Barie, M.D.: How will the practicing general surgeon be convinced that a particular enhancement to the suture material is going to provide protection against post-operative wound complications?
Henri R. Ford, M.D.: As I sit here thinking about the value of suture material, one potential issue is how long the suture material persists in the incision and whether that is altered by the presence of infection. Would triclosan on suture material persist in the incision for a prolonged period? Let's think about that. Vicryl* persists for 6-8 weeks, during which time bacterial colonization of suture material becomes progressively much less of an issue. If a late wound complication were to occur, such as a suture sinus, there's either no need to go after it surgically, or one can just do some local wound intervention and take care of it. After having adhered to all the proper prophylactic measures, if new suture material would now allow me to close primarily all grossly contaminated wounds that heretofore would have had to be left open, then there would be a huge potential use for such a product.
Ansgar O. Aasen, M.D.: Both the diameter of the suture and the length of the incision impact on how much suture material is implanted. Most suture material is not implanted in the subcutaneous tissue. Usually, one does not suture skin with a braided absorbable suture either, except for some subcuticular sutures. Most implanted suture is placed at the level of the fascial closure.
Donald E. Fry, M.D.: That is also the dependent part of the abdominal wall closure, the area where the blood and the serum tend to settle. It is probably the environment immediately above the fascia where conditions are optimal for bacterial growth and that fosters the infection. Moreover, the knot is the area where bacteria are likely to sequester and from where most infections arise, because of the interface between bacterial inoculum and ischemic tissue. To me, it makes good sense that the fascial suture is probably what we need to have impregnated. Showing zones of inhibition and a reduction of viable inoculum in knots themselves, in my view, would be compelling information.
Eugen Faist, M.D.: Many surgeons prefer monofilament absorbable suture for fascial closure. Prolene® is inert but permanent. Many surgeons no longer prefer it for fascial closure because the big knot results in a palpable mass in thinner patients, a source of concern to both patient and surgeon. An absorbable suture such as PDS-II®, particularly if placed with a continuous technique, makes for fewer knots in the wound and I think therefore makes for fewer infections in the surgical site. Perhaps that would translate into a lower rate of infection, but I believe it would be beneficial to coat or incorporate triclosan into non-absorbable sutures as well.
Doctor Barie: Let's talk about some of the complexities of surgical site infection (SSI) clinical trials. There are problems of definition. There are problems with long-term observation. There are problems of follow-up and, especially for clean surgical procedures, a low baseline incidence of infection to begin with, meaning that sample sizes need to be huge.
Doctor Fry: There is also technical variability to consider, as well as the need to characterize and stratify patients by risk. For example, the evidence is becoming clear that patients with hypoxic lung disease have higher SSI rates, in which case the same operation in Albuquerque, New Mexico probably carries a different rate of SSI than it does in San Diego just by virtue of differences in humidity and altitude. There are relatively few clinical situations where the infection rate is high enough that you could anticipate being able to show a clinical difference in SSI in a reasonably sized study of 400-500 patients. One scenario that might be appropriate would be cesarean section, as the procedure carries a reasonably high infection rate, and Vicryl* is used commonly for the fascial closure. Perforated appendicitis would be another area to study, but again, there is a wide variety in the degree of contamination.
Toni Hau, M.D.: Using suture material to deliver an antimicrobial agent into the wound is definitely interesting. Another aspect to consider would be that a large concentration of a substance could be delivered into a wound if coated material were woven into mesh.
Doctor Ford: One of the things we have started to do in our hospital and throughout the entire university system is to look at how much it costs different surgeons to do the same procedure. You know where we're going to go with that. If it costs the hospital $500 for one surgeon to repair a hernia whereas it costs someone else $1,000 to do the same operation, there is a problem for both the institution and the more expensive practitioner. That surgeon will be targeted to achieve cost reduction. If unmodified suture costs the institution $1 and the coated suture costs more, we have to be able to justify that increased expense by demonstrating a reduction of infection rate, hospital stay, or some other tangible improved outcome and cost savings. Perhaps the ability to close a high-risk incision that would previously have been left open might be a demonstrable benefit in terms of a shorter hospitalization, or none at all, or decreased expense for home care supplies and nursing visits. If SSIs could be reduced in incidence, that would translate into at least 2 days' shorter hospitalization and real savings of thousands of dollars per case.
Doctor Barie: There are no data to support the nearly universal practice of antibiotic prophylaxis of groin hernioplasty with mesh. Could a placebo-controlled trial of implanted triclosanimpregnated Prolene® mesh, were it to be developed, be justified ethically for inguinal hernia repair?
Doctor Fry: Medico-legal issues in the United States might make it difficult to deliberately not use peri-operative antibiotic prophylaxis when you know you are going to put mesh in, so the trial would have to use the same mesh, treated versus untreated, along with antibiotic prophylaxis, in my opinion. Another study might be interesting to do with trauma patients. Trauma patients have a high probability of reoperation. If coated PDS-II® becomes available, one could do some quantitative cultures of the coated versus the uncoated suture on the reoperative patients. Human data that support your basic contention that there are few microorganisms in the knot would be valuable.
Doctor Barie: As experts in surgical infection, what do you believe will convince the general surgeon in practice, who has to deal with SSIs but who does not have your specific interests and expertise in infection, to use a product such as this?
Doctor Fry: Innovation is part of responsible market leadership. Innovation advances technology and improves care, but also maintains market leadership. I believe that coating suture material with triclosan is a real innovation. The practicing general surgeon should rely on evidence of safety, biocompatibility, similar handling characteristics, wound healing, and microbiology. There is no practical short-term prospect for a suture material coated with an antiseptic to demonstrate better SSI rates, because a study with sufficient power to prove that hypothesis will take a long time to complete.
Doctor Barie: There have been many experiments done through the years of the admixture of antibiotics with vascular prostheses -- an obvious hypothesis, never proved.
Doctor Fry: Correct. Never proved. I would emphasize that we are hamstrung by sample sizes and our statistical methods, and the reality that there are no two treatments that are, in fact, identical. If we were able to do a study of 100,000 subjects in a controlled clinical trial, it is likely that statistically significant differences could be demonstrated for any number of different treatments, but what difference would it make for the individual patient? All of the trials of antibiotic treatment of bacterial peritonitis have concluded that monotherapy is similar to combination drug therapy, and that no regimen is superior.[1,2] Only after 25 years, dozens of trials, and thousands of enrolled patients is there a statistical suggestion that aminoglycoside-containing regimens may be inferior.[3] In a prospective study of 100,000 inguinal hernias, done with similar techniques by a capable group of people and randomized so that 50,000 patients receive triclosan-coated suture and 50,000 receive conventional suture, a 0.5% difference in SSI rate would be detectable. In clinical terms, the result is probably irrelevant, because, in practice, individual variations in technique and patient variables would still obscure any perceptible difference.
Doctor Ford: We all look for the best out-come for our patients. This is really what we want to see. Given that you can make the argument that the knot is the repository for the bacteria in the surgical site and the location where wound complications are likely to begin, it makes sense that the practicing surgeon would want to give each patient the best chance for minimizing or avoiding wound complications, especially of a contaminated incision.
Doctor Fry: An antibacterial substance needs to be in a wound for only a brief period of time to be effective, perhaps as little as the first 24 h following wound closure. Persistent antibacterial action until an absorbable suture degrades is not going to be necessary. Incorporation of a drug into suture material so that controlled release occurs, rather than coating the suture, might allow the development of a new drug delivery system. I have in my mind's eye making PDS beads that have drugs incorporated into the matrix and being able to give a 30-day dose of a drug with a single intramuscular injection, and have sustained release as the pellets degraded.
Doctor Barie: I see two issues here. On the one hand, there is the use of the material in a different formulation to deliver a drug. The second issue is to use the suture as a drug delivery system; for example, to deliver a local anesthetic to the wound.
Doctor Fry: That's another terrific idea. With the COX-2 inhibitors, for example, administering a type 2 cyclooxygenase inhibitor locally in the wound by this kind of a delivery system is a tremendous idea. But again, beyond the 5-10-day lifespan of the inflammatory process, I don't see any advantage to having sustained release medication delivered to an incision.
Doctor Hau: Are we certain that triclosan does not impair wound healing?
Doctor Barie: I would incubate triclosan with fibroblasts in culture.
Doctor Fry: I would agree. Such studies are important to see whether triclosan has adverse effects on basic wound healing, and on neutrophil and monocyte activity with respect to wound healing in particular, because chlorinated or iodinated products interfere with certain phagocytic and lysosomal functions of the white cell.
Doctor Barie: When you first heard of triclosan, what was your reaction? My first reaction was that I knew that it was an antiseptic, but I had no idea of its pervasiveness in our current society.
Doctor Fry: That was my initial reaction as well. What about the potential problem of the development of resistance when an antiseptic is used as an antibiotic? When antibiotics are given, inevitably resistance will begin to develop. However, that has not been the general result when chemical antiseptics have been used. They have stood the test of time and maintained their activity. Infectious disease consultants invariably worry whenever something is used that does not kill all bacteria absolutely. I would argue that an absolute bactericidal effect is totally unnecessary here. The spectrum of activity of triclosan is perfectly appropriate for its purpose in this situation.
Doctor Barie: One must remember that, in most cases, suture materials are implanted in clean or clean-contaminated incisions, not contaminated or dirty incisions. Gentle handling of the tissues, meticulous technique, and the other factors discussed are of paramount importance, so as to cause minimal perturbation of the wound until local host defenses recover. How quickly do local wound host defenses re-cover? The answer is they recover faster if you beat up the incision less.
Doctor Fry: Host defenses also recover faster if there are fewer potential replicating microbes that have a head start on the process, which is at the heart of the rationale of coating sutures with an antiseptic.
Doctor Barie: Doctor Ford, what do you believe? Among all of the salient factors related to the biology of the healing wound, what are the most important aspects of host defense to preserve, so as to promote optimum wound healing?
Doctor Ford: You cannot afford to impair monocyte/macrophage function and certainly not neutrophil function.
Doctor Barie: So you would recommend that it is very important to test triclosan in vitro against a standard battery of neutrophil and mononuclear cell functionalities?
Doctor Ford: Yes, absolutely.
Doctor Barie: What are some of the other critical features of wound host defense? What about wound protein synthesis? Fibroblasts can grow or not, but they also have to function.
Doctor Ford: We must be certain that there are no negative impacts on the beneficial effects of inflammation that contribute to normal wound healing. Neutrophils and monocytes/macrophages only function in the wound after they have been recruited by the chemoattractants that are generated as part of the initiating events of inflammation. I would want to be certain that there are no fibrinolytic or anticoagulant effects, no effects upon platelet aggregation, and no effects on complement activation. Another important question is, what do we know about allergic reactions to triclosan?
Doctor Barie: Triclosan is incorporated into at least one popular brand of toothpaste. Dermal challenge studies of volunteers dosed at 20 times the dose that would be delivered by swallowing the toothpaste resulted in no allergic reactions. Moreover, blood testing of the volunteers before they were challenged with the triclosan revealed that every one of them had a detectable concentration of triclosan in their blood. It is ubiquitous. Safety in children has been confirmed also.
Symposium and Panel Discussion held at the Combined Annual Meetings of the Surgical Infection Society and the Surgical Infection Society-Europe, Madrid, Spain, May 4, 2002.
Address reprint requests to: Philip S. Barie, M.D. Department of Surgery, Payson 713A, New York-Presbyterian Hospital, 525 East 68 Street New York, NY 10021. E-mail: pbarie@med.cornell.edu
© 2002 Mary Ann Liebert, Inc.
Cite this: Current Issues in the Prevention and Management of Surgical Site Infection - Part 2 - Medscape - Dec 01, 2002.
