The reason medicine is so passive when the surgical site infection progresses to full wound ... ment (especially a host environment) is the biofilm phenotype.
Surgical Site Infection Millions of times each year, surgeons and the patients they treat are confronted with a surgical site infection resulting from a procedure intended to make the patient better. In fact, 8.5% (2-14%) of all surgeries are complicated by wound infections. Yet it would be impossible to overstate the despair and frustration that wells up in each individual surgeon while they impotently watch the wound dehisce. What they meant for good is now insidiously and relentlessly causing harm to the patients they care for. The reason medicine is so passive when the surgical site infection progresses to full wound dehiscence may be that we simply do not understand the process at the molecular level. Much of this confusion may directly relate to a lack of understanding of bacterial biofilm and the role of this radically different type of bacteria in surgical site infections. This lack of understanding has led to much difficulty in our diagnosis, terminology, and treatment of surgical site infections. Although bacterial biofilm is not well understood or even accepted in medicine, biofilm is well known in the literature concerning industry, food processing, manufacturing, and especially dentistry. The preferred state for bacteria to exist in any environment (especially a host environment) is the biofilm phenotype. Biofilm phenotype bacteria are just one phase in the life cycle of a bacterium. The reproductive phase of bacteria is mostly comprised of single cell bacterium (planktonic) that are free floating or sometimes motile that seek out different environments for which the bacterium can succeed and perpetuate itself. Ninety-nine percent (99%) of bacteria identified in the environment are organized in biofilm communities. These communities are quite different than the single cell bacterium we have learned in our microbiology studies. Once a single cell bacterium attaches to a surface it rapidly changes the proteins it expresses becoming phenotypically much different than its free floating state. As the bacterium divides in its attached area, it self-secretes a matrix material composed of polymeric sugars, proteins, and/or DNA. This matrix material protects the early microcolony from environmental and host stresses. As the microcolony continues to divide, it reaches a quorum—that is, a critical density—of bacteria that allows the microcolony to mature into a biofilm. The hallmark of mature biofilm is that it develops 3-dimensional structures, such as growing up off the surface, organizing around capillaries down into the host, developing mushroom-like towers to interface with the environment, and several other morphologic features. In the host, biofilm is able to highjack host components such as fibrinogen, neutrophil DNA, and collagen to incorporate into its protective matrix, making it impervious to host attacks. Biofilms are totally unperturbed by activated macrophages, neutrophils, antibodies, compliment, or other host defenses. Biofilms are also resistant to biocides, drying, overhydration, or other environmental stresses. It is easy to understand how biofilm phenotype bacteria are so very different than the individual bacteria that are grown up on agar culture plates. The differences between planktonic and biofilm phenotype bacteria become very important when we view their interaction with the host. Planktonic bacteria are competitive. When two planktonic bacteria are placed on an agar plate with the appropriate nutrients (the agar maintains the planktonic phenotype) the two planktonic bacteria will compete. The dominant species will claim the entire plate. This is similar to what is observed in planktonic infections in humans. Infections that are predominantly caused by bacteria in planktonic phenotype are characteristically described as acute infections. These infections tend to be progressive with a significant host response described by the classic signs of celsus, including erythema, pain, swelling, and heat. The hallmark of acute infections is they are susceptible to antibiotics and quickly resolve in a 10-14 day course of treatment. The natural history of acute infections is they arise quickly, progress causing tissue destruction and then totally resolve. Planktonic phenotype bacteria explain much of this behavior. Planktonic bacteria upregulate virulence factors, proteases, and other secreted agents to lyse tissues on which it feeds itself. The perceived pattern of acute planktonic infection is one of predation: if the host does not adequately respond or if there is not an outside intervention, then the host dies. The infection caused by biofilm phenotype bacteria is in stark contrast. Once biofilm is established on the surface of the host, regardless of the environment (sinus, gut, and skin), it exhibits a significantly different strategy for the community’s survival. Biofilm produces a hyperinflammatory milieu. This inflammatory state produces exudate from surrounding capillaries that percolates through the biofilm, and nutrients can be extracted. This allows the biofilm to maintain the security of its surface attachment and still feed indefinitely. This pattern of infection is much more consistent with a parasite than a predator. The natural history of chronic infections is quite different from those of acute infections. This difference is best explained by biofilm. Chronic infections follow a persistent undulating course with frequent exacerbations. Chronic infections respond incompletely to antibiotics and reemerge once the antibiotics are withdrawn. A hallmark of many, if not most, chronic infections is
that they will respond marginally to antibiotics as well as immunosuppressants like steroids. The response of chronic infections to steroids is indirect evidence that the inflammation producing plasma exudate in the area of the infection is necessary for the success of the biofilm. Biofilm explains many of the wound behaviors seen in surgical site infections. Many surgical site infections occur after discharge and show a slow undulating course much different than an acute infection. Often the entire incision will dehisce but there is no degradation of tissue surrounding the wound. The damage appears to be confined to the surface of the surgical incision. Biofilms are more successful on surfaces and especially surfaces that contact one another. Also, even though adequate clinical cultures are obtained that demonstrate at least some of the bacterial species contained in the surface associated bacteria of the wound, antibiotics are unsuccessful in clearing most of these infections. Biofilm phenotype bacteria on the surface of the surgical wound explain why we stand by helplessly while our planktonic tools and strategies fail to prevent the wound from dehiscing. Biofilm management of surgical site infections is based on multiple concurrent strategies specifically targeting biofilm behavior. This includes opening the wound of any tunneling and undermining by removing sutures or opening skin to expose the surface associated bacteria. This robs biofilm of a second surface to organize around, and it also allows access for other strategies. The biofilm can be robbed of its nutritional source by immunosuppressants, but this also blocks host healing responses and should be considered a last resort in surgical site infections. However, negative pressure wound therapies can accelerate the transit of exudate through the biofilm, thus preventing full extraction of nutrients. Frequent debridement of the surface of the wound forces the biofilm to constantly reconstitute itself and makes it more susceptible to antibiotics and selective biocides. By using antibiotics at biofilm doses (think endocarditis, osteomyelitis) for long periods of time improves suppression of the biofilm. Antibiotic alone can and will never be successful against biofilm phenotype bacteria and should only be used in conjunction with other strategies. Selective biocides such as silver, cadexomer iodine, etc. will suppress biofilm phenotype bacteria up to one half log but does not harm host healing responses. The use of multiple concurrent strategies specifically targeting biofilm phenotype bacteria has been successful in healing surgical site infections. The four case histories included illustrate important clinical points in managing surgical site infections. The first case, seen in Figure 1, illustrates a counterintuitive point that the more aggressively the wound is opened the quicker it heals. Figure 1.a shows the wound one week after sutures have been removed and the surface of the surgical wound aggressively debrided and all undermining opened at the distal end. In just a little over two weeks the entire plantar portion of the wound is healed (Figure 1.b). This study demonstrates that when biofilm is adequately suppressed, the wounds heal at about the same rate as an acute wound (a wound without biofilm). This is true even in a patient with diabetes. The second case is also a plantar wound in a diabetic patient (Figure 2). This case illustrates that trying to keep the wound artificially “pulled together” by leaving some of the sutures is unnecessary. By opening the wound and removing surfaces that touch produces two beneficial effects. First, biofilm is more easily suppressed and second the wound can contract at very high rates. The third case illustrates the dangers of trying to hold the wound together when biofilm has obviously taken over. The patient presented with a painful stump draining at many areas with very poor color and necrosis along the wound margin. By leaving the staples in, the time to complete healing was markedly delayed. It should be noted that the patient had exposed bone in the base of the wound with the distal end being very soft, consistent with osteomyelitis. The patient was able to heal over his exposed, infected bone to become a functional prosthetic wearer. Aggressive, early removal of sutures/staples, opening, undermining, and removing devitalized tissue markedly improves the time to healing. Case four demonstrates the ability to heal over infected implanted medical devices (Figure 4). The number of implanted medical devices rises each year and so do the number of postoperative infections. Current treatment for infections of implanted medical device is removal. With biofilm based strategies many of these infected devices can be left in place and the wound can be healed.
Conclusion Bacteria living in a surface-associated colony have been recognized for decades and are now a well-established medical fact. Biofilm’s role in chronic infections is just now being appreciated and widely becoming accepted. Surgical site infections have many of the characteristics of chronic wounds specifically and chronic infections in general. Therefore, an understanding of biofilm phenotype bacteria may be important in the management of surgical site infections. Communication molecules within the community regulate the protein expression of an individual bacterium within the biofilm. These communication molecules are termed quorum-sensing molecules, and they regulate a number of pathways within the bacterium, causing up to 800 new proteins to be expressed. Change in biofilm from the freefloating state to a member of the community is just as radical as the metamorphosis of a caterpillar into a butterfly. Even after such a radical transformation, both are genetically identical yet phenotypically quite different. This change into the biofilm state along with the protective matrix that attaches the community to the host provides incredible protection. The host proteases, white blood cells, antibodies, and other host defenses are only minimally effective against the biofilm. Therefore, any efforts to “improve the host,” such as improving blood sugar, correcting anemia, or managing other systemic diseases, only makes small incremental improvements in wound healing. These host issues must be addressed, yet the major barrier to surgical site infection healing is the infection itself— the biofilm. Biofilm is best managed through physical disruption. This principle has been proven in our tubs, toilets, and on our teeth. It has also been demonstrated in packaging, processing and pool maintenance. By frequently disrupting the biofilm with brushes, or by other physical, means the colony is disrupted. Then, as the colony tries to reconstitute itself, treating agents such as biocides, antibiotics, and even quorum-sensing inhibitors become much more effective. This principle of physical removal of biofilm with a transient increased vulnerability can be exploited in surgical site infections in several ways. Consider a quick opening of the involved area of the wound, removing any dead and devitalized tissue frequently, and then managing the surface of the wound to suppress the reaccumulation of biofilm at weekly intervals. As efficacious as physical disruption of biofilm is, it is rarely sufficient. By adding other simultaneous strategies such as selective biocides, anti biofilm agents, and antibiotics, it is often possible to suppress the reaccumulation of wound biofilm. By suppressing biofilm, host healing processes like angiogenesis, extracellular matrix formation, and wound contraction becomes much more effective. It has been demonstrated that by targeting biofilm, a higher percentage of chronic wounds heal demonstrating that biofilm is an important barrier to wound healing. This information suggests that early intervention with aggressive, multiple concurrent strategies targeting the surfaceassociated bacteria on the surgical site infection will result in improved outcomes for these wounds.
Case 1
Figure 1.a
Figure 1.b
This 53-year-old white male with over 30 years of insulin dependent diabetes mellitus was suffering from peripheral neuropathy. The patient stepped on a nail while mowing his lawn. This resulted in osteomyelitis of the second ray with purulence throughout the forefoot. The patient demonstrated marginal TCpO2 of the foot of 24, a hemoglobin A1C of 9.3 and a prealbumin of 10. The patient underwent an extensive surgical debridement on 7/10/05. There was a repeat surgery on 7/14/05 at which time the plantar surface was closed and surgical drains were placed in the dorsum of the foot. On 8/03/05 the plantar wound was bulging at the areas of drainage between the sutures and showed necrosis of the skin margins. The sutures were removed. Undermining at the distal end of the wound was opened and the surface of the wound was managed using curette and ultrasonic debrider. By 8/25/05, the patient’s wound was starting to granulate and showed wound contraction. Over the next 18 days the patient completely closed the plantar wound despite high blood sugars, poor nutrition and continued ambulation in a walking boot. This demonstrates that by targeting biofilm, even in the presence of unmanaged host factors, wound healing can be quite dramatic.
Case 2
Figure 2
This patient is an insulin dependent diabetic from childhood. He is a 54-year-old white farmer, who developed a wound on his plantar surface, which eroded through the forefoot and back to the heel. He underwent extensive surgical debridement with primary closure on 7/05/05. In the hospital the wound began to show color changes, necrosis at the margin along with swelling of the plantar surface of the foot. Several sutures were removed from the wound to allow drainage and some of the necrotic material to be removed. However sutures were left in the midportion of the wound in an effort to “hold together” the wound. We were asked not to remove the sutures. Biofilm has a significant advantage when host surfaces covered with biofilm touch one another. Once the sutures were removed on 7/14/05 the wound rapidly contracted, displayed new granulation tissue and reepithelialized. Although sutures can make the external manifestation of the wound look smaller and therefore “better”, sutures are counterproductive. After identifying a wound that has chronic infection (biofilm) as evidenced by periwound color changes, edema, drainage, softness of underlying tissue, hiding this nidus of infection is detrimental. Aggressively opening the area and pursuing concurrent strategies to suppress biofilm can salvage much of the rest of the normally healing wound.
Case 3:
Figure 3
This is a 39-year-old Hispanic male with juvenile onset diabetes mellitus. His blood sugars were poorly controlled. The patient has severe peripheral neuropathy and developed osteomyelitis of his foot. This required a below knee amputation on Christmas day, 2001. On January 2nd, the patient was discharged with a swollen, tender stump with necrotic borders and drainage from several areas of the wound. The patient was referred for hyperbaric oxygen, which he could not pursue because he lived over 300 miles from the unit. The patient returned on 1/22/02 with staples still in place, necrotic tissue and exposed bone. The end of the bone was soft, consistent with osteomyelitis. By pursuing aggressive opening of the wound, frequent debridement of the surface of the wound and multiple strategies to suppress reaccumulation of biofilm the patient showed rapid closure with a closed, well-shaped stump by July of that year. Even if deep structures are involved in a surgical site infection and especially if there is local osteomyelitis, aggressive management of biofilm can accomplish complete wound healing without further surgery.
Case 4
Figure 4
This 64-year-old German female was approximately 2 weeks out from instrumentation of her spine when she presented with a nonhealing surgical wound on 8/25/03. The patient had been placed on antibiotics since the time of her surgery yet the wound had only worsened. On 8/25/03 the undermining between the two wounds was opened up and the undermining around the edge of the wound was addressed. The soft area over the infected hardware was removed exposing one screw head and metal in two other areas of the wound. One month later the erythema had resolved, drainage was under control and important to the patient the pain had pretty much abated. Although the wound bed was not granular there was evidence of wound contraction. Over the next 5 months the wound moved to complete healing. By February of 2004 the patient’s wound was completely healed and there has been no recurrence. This case demonstrates that by frequent disruption of biofilm with multiple agents to prevent its reaccumulation that even metal that clearly is associated with biofilm that complete coverage of the implanted medical device and wound closure can be accomplished.
