Infection Control Today - 11/2003: Surgical Prophylaxis

Surgical Prophylaxis: Perioperative Antibiotics Are No Longer Voodoo Science

By Kathy Dix

It is no secret that surgical site infections are one of the most prevalent problems in hospitals. And since the widespread use of penicillin in WWII, it has been no secret that antibiotics work against them. But some physicians have been loath to utilize the shorter regimens of perioperative antibiotics recommended in recent literature.

No one questions the ability of antibiotics to prevent surgical wound infections; this has been well-understood since the 1960s, explains Joseph S. Solomkin, MD, professor of surgery and director of research in the Trauma and Critical Care division of the University of Cincinnati College of Medicine. Most procedures require antibiotics administered once in the immediate preoperative period, he notes. Depending on the length of the procedure and the half-life of the drug given, an intra-operative dose may be needed. Twenty-four hours total is acceptable, but again, most data indicate only the preoperative dose is needed.

Ideally, the best time to initiate preoperative or perioperative antibiotics is several days or even the day before, depending on the antibiotic chosen, says Fred Pescatore, MD, a physician in private practice in New York City and the author of several texts on allergies, asthma and proper nutrition.

Shorter Regimens; Same Results

William Carroll, MD, a head and neck surgeon at the University of Alabama at Birmingham (UAB), covered the topic of surgical prophylaxis in a recent scientific paper. According to the results of his recent study, it is safe to use fewer antibiotics during free-flap reconstruction. Five to seven days of antibiotics were once thought necessary to prevent infection after cancer surgery, he recounts. Thats been shortened today to only 24 hours without significant increase in infections.

That is a recommendation that some physicians dont trust, however. Many surgeons of head-and-neck cancer, however, still hold to the old standard when reconstructive surgery requires covering the lost tissue with tissue from another part of the body. Loss of a free-flap to infection in this highly contaminated area is so devastating that many are hesitant to adopt short-course preventive antibiotics, says Carroll. He headed a prospective, randomized comparison of both regimens, reported in the July 2003 Archives of Otolaryngology Head & Neck Surgery. The study showed that infection rates were very similar between the two, justifying prophylactic use of the antibiotic for 24 hours from the time of surgery, Carroll continues.

In this paper, we were trying to show that a short course is effective for a very specific sub-group of head-and-neck cancer patients. Peri-operative antibiotics have been shown for many years to be effective in preventing infection in many surgical sites. Most head and neck cancer wounds are clean-contaminated and infection rates as high as 70 percent are seen with no antibiotics. In the head and neck, the antibiotics can be systemic (IV) or topical irrigations of the wound with comparable results, he adds.

As with any antibiotic regimen, there is a time frame in which the administration of the drug works most effectively. It is helpful to give the antibiotics an hour or more pre-op so that there is good tissue penetration at the time of skin incision, Carroll recommends. Because such administration is prophylactic rather than reactive, the less antibiotic exposure, the better. Antimicrobial resistance is more a concern if there is already a problem; if you cut short a course of antibiotics that are being used to treat an existing infection, there is a risk of selecting out more resistant bugs, he says.

Probiotics

Probiotics are a sometimes-controversial possibility for improving the bodys immune response. Some physicians view them with a certain degree of suspicion, perhaps because their use is not regulated by any government body. Probiotics are gaining mainstream acceptance slowly but surely, says Pescatore, who uses probiotics in his daily practice. There is a lot of scientific data to confirm using them in the treatment of diarrhea and Crohns disease, as well as in surgical use when the patient is pre-medicated with antibiotics, as they will replenish the intestine with the natural bacteria found in our bowel tract, he says.

Pescatore has been utilizing probiotics for some time, and, he says, I have been convinced of their efficacy for the past 10 years. They markedly decrease vaginal yeast infections in women and by extension would markedly decrease intestinal overgrowth of yeast, which could lead to chronic fatigue, gastrointestinal upset and other decreased immune function.

Probiotics can effectively maintain the proper balance of good bacteria in the bowel tract, he notes, adding, The immune system is focused in the GI system (70 percent) and if that balance is out of whack, then there can be many problems associated with an imbalanced immune system susceptibility to colds, and the ones I mentioned above. Probiotics are used almost routinely in Europe to guard off yeast infections, as both good and bad bacteria are killed when antibiotics are given; this leads to less loss of work and other infections caused by a suppressed immune system.

The issue is really that theres no harm to (probiotics), so a lot of people say, Sure, go ahead and try it, see if it helps, but dont study it or you never really know if it works or not, says Jeffry A. Katz, MD, associate professor of medicine at Case Western Reserve University School of Medicine in Cleveland. Katz, a gastroenterologist whose focus is inflammatory bowel disease (IBD), notes the benefits of probiotics in treating pouchitis, a complication of pouch surgery for ulcerative colitis.

Katz, who frequently sees patients with Crohns disease and ulcerative colitis (UC), primarily uses probiotics in therapy of mild ulcerative colitis or mild Crohns disease. Most of the benefits that Ive seen are in people with mild UC, he says. The evidence for their greatest efficacy probably comes from pouchitis, [which] occurs after patients with UC have had major surgery and have had their colons removed. The surgeons construct a pouch out of small intestine and sew that to the anus and those pouches sometimes become inflamed. In that situation, probiotics, particularly a probiotic called VSL#3, have shown significant efficacy both in preventing recurrence of pouchitis, in prophylaxing against the development of pouchitis, and also some preliminary data suggesting benefit in the treatment of active pouchitis.

Pouchitis, Katz notes, shows evidence of being related to a disorder of microbial ecology in the surgically constructed pouch; probiotics are thought to change that microecology. Its not exactly clear how probiotics work, but there are a number of possibilities, he says. One: they might antagonize unwanted or deleterious or pathogenic bacteria. Two: they may stimulate the colonic or small intestinal epithelium to produce substances that are protective or beneficial. Three: possibly they alter the immune response in the gut, and that might affect some of the symptoms that our patients with IBD have. They may also have benefits just by changing the fecal pH and that might affect other bacteria or the mucus or the colonic epithelium. However, he cautions, these are hypothesized actions. But its been shown pretty clearly that probiotics seem to stimulate anti-inflammatory cytokines or regulatory cytokines and that in turn has a suppression on proinflammatory cytokines. Probiotics are being used to treat other disorders besides IBD, Katz continues. They have been acknowledged since the research of Mechnikov, who won a Nobel prize for his work in 1908. Europeans have embraced them, and alternative/complementary medicine has been utilizing them for some time. There is a lot of literature on probiotic effects in diarrheal diseases in children, where probiotic therapies have been shown in diarrheal diseases in children to be effective at in a variety of situations in prophylaxis, in third-world countries, in shortening duration of diarrhea, in hospitalized patients, in shortening duration of diarrhea in outpatients with acute diarrhea, and in the treatment of antibiotic-associated diarrhea, Katz notes.

In addition, theres some evidence that probiotics can be useful to prevent recurrence of c. difficile diarrhea. The treatment of c. diff is with antibiotics, but after those antibiotics are stopped, it can often recur, up to a dozen times. If probiotics are given to treat c. diff, theyre typically given for a month to three months. With probiotics, it seems that the body is able to get the normal ecology reestablished and prevent the recurrence of this particular kind of infection, he points out.

Surgical infections are an entirely different category, however. Could you prevent postoperative infections or decrease postoperative infections by establishing a more friendly intestinal environment? Theres some logic to that. Is there proof of that? Not that Im aware of, Katz says.

At least in animal models, probiotics have been shown to increase the barrier function of the intestine, so it improves intestinal permeability, meaning that it strengthens the intestinal barrier so things cant get through, he adds. Animals treated with probiotics are less susceptible to invasion by a variety of organisms in the laboratory salmonella organisms, for example.

Gastroenterologists are also investigating the possibility that VSL#3 can decrease postoperative recurrence of Crohns disease. However, a great deal of study is still necessary, Katz says. Its not clear, for example, if all probiotics are the same presumably not its kind of a poorly regulated, governmentally regulated industry. We did a study where we just looked at 17 or 18 probiotics that we bought in a health food store and we found that the strength, or what you can grow out of each capsule, packet or powder, is in about 50 percent at least a log order of difference in strength. Theyll say 10 billion and youll be able to get 1 billion, or theyll say 1 billion and youll be able to get five hundred million or a hundred million, so its not clear how much youre getting when you buy a lot of [probiotics] that are available over the counter.

Furthermore, we dont know whether one probiotic, say, lactobacillus gg, is better than a mixture of probiotics. VSL#3 is actually eight different species mixed together at a very high concentration. VSL#3 is what Im familiar with, but theres some information available on lactobacillus gg in diarrheal diseases, for example. Is one better than eight probiotics or six or four, or is the same probiotic good in all diseases, or is one better for IBD and one better for postoperative prophylaxis? We really dont have any of this information.

Regardless of which probiotics are most effective, Katz affirms that they are still firmly identified with the realm of alternative or complementary therapies. Proof of benefits (from probiotics), except for a few very specific instances, remains to be shown. But the potential benefits are profound. Since the bacteria in the body are involved in metabolism of nutrients, theyre being looked at for the control of cholesterol; theyre being looked at in the management of kidney stones because there are certain bacteria that can help metabolize nutrients to decrease the chance of getting kidney stones; theyre being looked at in colon cancer and colon polyp prevention. These are all areas of investigation, but theyre all very early.

When asked about the potential adverse events associated with probiotics, Katz draws on experience from his own practice. Usually there are no side effects; the common side effects, if any and again, most people tolerate these without problems are a little bloating, or some change in bowel habits either the stool becomes firmer or the stool becomes a little looser but I would say that 80 percent have absolutely no side effects. Theyre very safe ...these are not pathogenic organisms, so theyre very unlikely to cause harm or illness. There have been occasional reports of bacteremia with lactobacillus gg, but that lactobacillus is known to be able to cause bacteremia. Its very rare.

Although the dosage seems high, it does not even approach the level of existing colonic flora. In your intestine, in your colon, theres about 10 to the 13th bacteria, and the most that anyone ever takes ... would be 10 to the 11th or so, so youre way below the levels of bugs already in the colon, observes Katz.

Its still worth keeping an open mind about their potential benefits, and I think whats needed is careful scientific study with careful analysis of the results, he says.

Probiotics have a limited but useful role in certain settings, Solomkin remarks. They are not embraced widely. The data that they are effective is not there. It is largely theoretical and anecdotal. The problem is that it is very difficult, if not impossible, to get a probiotic to persist in the gastrointestinal tract.

Staying Power

Bear in mind, probiotics are supplements and not considered drugs, so certain claims need to be proven, says Mark A. Brudnak, PhD, ND and senior executive vice president of MAK Wood, Inc. What we have found is that even if we feed dead probiotics, in the billions, to people, they will have increased levels of certain immune parameters that tell us the probiotics are priming or bringing the body to the first level (of immune cascade). Typically, for an immune cascade, there are two levels required to be reached, he says.

Think of it as a curve that goes up, levels off and then goes higher again, and levels off. The X axis is time, the Y axis is immune cells number (or whatever immune parameter is measured, such as cytokine levels). The first level is the potentiation level where the immune system first recognizes a foreign object (antigen) and then tells all the other immune cells (on a needto- know basis) what it saw. If the antigen is present at high enough levels, a full-blown immune cascade will ensue, involving many immune cells. This can take up to one to two weeks for the first level, then another week or so to get to the highest part of the second level.

That is when the immune cascade is in full swing and ripping into the foreign cells. If the immune system clears the antigens, then it remains at that level, but doesnt go back below it. Eventually, the body will go below it, though, explains Brudnak.

As an adjuvant, probiotics can help with things such as vaccines, because they can assist with increasing the immune sensitivity, he adds. They are only antibiotic in the sense that they can and do produce certain antibiotic substances, such as acidophilin, from L. acidophilus, collectively called bacteriocins However, in comparison to modern antibiotics, these are a little on the weak side.

Dosage of probiotics is in the billions, says Brudnak. Large companies such as that behind LGG sell these in the 20-40 billion per cap range; doses in tens to hundreds of billions have been used. That is not uncommon.

Brudnak has found that probiotics even assist in preventing caries. The idea of caries prevention came when I looked at the flora of the normal oral cavity and found that lactic acid bacteria are found there, he recalls. I couldnt understand why they would be needed, but I have had some subsequent discussions with other labs working in the area that think the same thing, that the probiotics are keeping the caries-causing bacteria in the mouth at bay. It is when they are out of balance, by not brushing and eating the right food (which probably means things that have a lot of probiotics like yogurt) that cavities occur. It is a neat concept for anyone looking for a new approach or application of probiotics. The research is slowly trickling out that probiotics may have a place in certain types of gums sold for oral health maintenance.

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