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 themost prevalent problems in hospitals. And since the widespread use of penicillinin WWII, it has been no secret that antibiotics work against them. But somephysicians have been loath to utilize the shorter regimens of perioperativeantibiotics recommended in recent literature.

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

Ideally, the best time to initiate preoperative or perioperative antibioticsis several days or even the day before, depending on the antibiotic chosen, saysFred Pescatore, MD, a physician in private practice in New York City and theauthor 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 atBirmingham (UAB), covered the topic of surgical prophylaxis in a recentscientific paper. According to the results of his recent study, it is safe touse fewer antibiotics during free-flap reconstruction. Five to seven days ofantibiotics were once thought necessary to prevent infection after cancersurgery, he recounts. Thats been shortened today to only 24 hours without significantincrease in infections.

That is a recommendation that some physicians dont trust, however. Manysurgeons of head-and-neck cancer, however, still hold to the old standard whenreconstructive surgery requires covering the lost tissue with tissue fromanother part of the body. Loss of a free-flap to infection in this highlycontaminated area is so devastating that many are hesitant to adopt short-coursepreventive antibiotics, says Carroll. He headed a prospective, randomizedcomparison of both regimens, reported in the July 2003 Archives ofOtolaryngology Head & Neck Surgery. The study showed that infectionrates were very similar between the two, justifying prophylactic use of theantibiotic for 24 hours from the time of surgery, Carroll continues.

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

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

Probiotics

Probiotics are a sometimes-controversial possibility for improving the bodysimmune 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, saysPescatore, who uses probiotics in his daily practice. There is a lot of scientific data to confirm using them in the treatmentof diarrhea and Crohns disease, as well as in surgical use when the patientis pre-medicated with antibiotics, as they will replenish the intestine with thenatural bacteria found in our bowel tract, he says.

Pescatore has been utilizing probiotics for some time, and, he says, Ihave been convinced of their efficacy for the past 10 years. They markedlydecrease vaginal yeast infections in women and by extension would markedlydecrease 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 inthe bowel tract, he notes, adding, The immune system is focused in the GIsystem (70 percent) and if that balance is out of whack, then there can be manyproblems associated with an imbalanced immune system susceptibility tocolds, and the ones I mentioned above. Probiotics are used almost routinely inEurope to guard off yeast infections, as both good and bad bacteria are killedwhen antibiotics are given; this leads to less loss of work and other infectionscaused by a suppressed immune system.

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

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

Pouchitis, Katz notes, shows evidence of being related to a disorder ofmicrobial ecology in the surgically constructed pouch; probiotics are thought tochange that microecology. Its not exactly clear how probiotics work, butthere are a number of possibilities, he says. One: they might antagonizeunwanted or deleterious or pathogenic bacteria. Two: they may stimulate thecolonic or small intestinal epithelium to produce substances that are protectiveor beneficial. Three: possibly they alter the immune response in the gut, andthat might affect some of the symptoms that our patients with IBD have. They mayalso have benefits just by changing the fecal pH and that might affect otherbacteria or the mucus or the colonic epithelium. However, he cautions, theseare hypothesized actions. But its been shown pretty clearly that probiotics seem to stimulateanti-inflammatory cytokines or regulatory cytokines and that in turn has asuppression on proinflammatory cytokines. Probiotics are being used to treat other disorders besides IBD, Katzcontinues. They have been acknowledged since the research of Mechnikov, who wona Nobel prize for his work in 1908. Europeans have embraced them, andalternative/complementary medicine has been utilizing them for some time. Thereis a lot of literature on probiotic effects in diarrheal diseases in children,where probiotic therapies have been shown in diarrheal diseases in children tobe effective at in a variety of situations in prophylaxis, in third-worldcountries, in shortening duration of diarrhea, in hospitalized patients, inshortening duration of diarrhea in outpatients with acute diarrhea, and in thetreatment of antibiotic-associated diarrhea, Katz notes.

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

Surgical infections are an entirely different category, however. Could youprevent postoperative infections or decrease postoperative infections byestablishing a more friendly intestinal environment? Theres some logicto that. Is there proof of that? Not that Im aware of, Katz says.

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

Gastroenterologists are also investigating the possibility that VSL#3 candecrease postoperative recurrence of Crohns disease. However, a great deal ofstudy is still necessary, Katz says. Its not clear, for example, if allprobiotics are the same presumably not its kind of a poorlyregulated, governmentally regulated industry. We did a study where we justlooked at 17 or 18 probiotics that we bought in a health food store and we foundthat 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. Theyllsay 10 billion and youll be able to get 1 billion, or theyll say 1 billionand youll be able to get five hundred million or a hundred million, so itsnot clear how much youre getting when you buy a lot of [probiotics] that areavailable over the counter.

Furthermore, we dont know whether one probiotic, say, lactobacillusgg, is better than a mixture of probiotics. VSL#3 is actually eightdifferent species mixed together at a very high concentration. VSL#3 is what Im familiar with, but theres some information availableon lactobacillus gg in diarrheal diseases, for example. Is one betterthan eight probiotics or six or four, or is the same probiotic good in alldiseases, 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 arestill firmly identified with the realm of alternative or complementarytherapies. Proof of benefits (from probiotics), except for a few veryspecific instances, remains to be shown. But the potential benefits areprofound. Since the bacteria in the body are involved in metabolism ofnutrients, theyre being looked at for the control of cholesterol; theyrebeing looked at in the management of kidney stones because there are certainbacteria that can help metabolize nutrients to decrease the chance of gettingkidney stones; theyre being looked at in colon cancer and colon polyp prevention. Theseare 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 sideeffects; the common side effects, if any and again, most people toleratethese without problems are a little bloating, or some change in bowel habits either the stool becomes firmer or the stool becomes a little looser butI would say that 80 percent have absolutely no side effects. Theyre very safe...these are not pathogenic organisms, so theyre very unlikely to cause harmor illness. There have been occasional reports of bacteremia with lactobacillusgg, 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 ofexisting 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 youreway 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 ofthe results, he says.

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

Staying Power

Bear in mind, probiotics are supplements and not considered drugs, socertain claims need to be proven, says Mark A. Brudnak, PhD, ND and seniorexecutive vice president of MAK Wood, Inc. What we have found is that even ifwe feed dead probiotics, in the billions, to people, they will have increasedlevels of certain immune parameters that tell us the probiotics are primingor bringing the body to the first level (of immune cascade). Typically, for animmune 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 higheragain, and levels off. The X axis is time, the Y axis is immune cells number (orwhatever immune parameter is measured, such as cytokine levels). The first levelis the potentiation level where the immune system first recognizes aforeign 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, afull-blown immune cascade will ensue, involving many immune cells. This can takeup to one to two weeks for the first level, then another week or so to get tothe highest part of the second level.

That is when the immune cascade is in full swing and ripping into the foreigncells. If the immune system clears the antigens, then it remains at thatlevel, 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, becausethey can assist with increasing the immune sensitivity, he adds. They areonly antibiotic in the sense that they can and do produce certainantibiotic substances, such as acidophilin, from L. acidophilus,collectively called bacteriocins However, in comparison to modernantibiotics, these are a little on the weak side.

Dosage of probiotics is in the billions, says Brudnak. Large companiessuch 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. Theidea of caries prevention came when I looked at the flora of the normal oralcavity and found that lactic acid bacteria are found there, he recalls. Icouldnt understand why they would be needed, but I have had some subsequentdiscussions with other labs working in the area that think the same thing, thatthe probiotics are keeping the caries-causing bacteria in the mouth at bay. Itis 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) thatcavities occur. It is a neat concept for anyone looking for a new approach orapplication of probiotics. The research is slowly trickling out that probioticsmay have a place in certain types of gums sold for oral health maintenance.