Infection Control Today - 01/2004: THE INVASION OF THE ANTIMICROBIALS

THE INVASION OF THE ANTIMICROBIALS

By John Roark

On both the consumer and healthcare front, there is a ubiquity of productscontaining antibacterial and antimicrobial properties. The question is, is thegerm-fighting enhancement necessary or useful?

Finding a simple household liquid soap product thatdoes not contain antibacterial chemicals has become a challenging pursuit. The utility of this sort of antibacterial product is based entirely oninference, says Bill Schaffner, MD, chairman of the Vanderbilt Medical Centerinfection control committee. As far as Im aware, there are no data tosuggest that the use of household soaps, cleaners, etc, are associated with areduction in either respiratory or enteric disease.

There are theoretical reasons to believe that they might be effective. But is the reduction greater than just using simple soap and water? Thatremains a big question mark, says Schaffner, And I think frankly in theminds of most infectious disease physicians and those involved in infectioncontrol, its a very dubious proposition. But it obviously has sales appeal.

The use of antimicrobial chemicals in commercial products has all of uscrossing our fingers and fretting, but there has been no real development ofresistance ... yet, he continues. Theres no scientific reason tobelieve that the use of Triclosan will predispose to resistance of bugs toconventional antibiotics. In fact, many of us are rather surprised that moreresistance has not yet developed. But it hasnt.

Does that mean that we should continue using them? I think thats aquestion that is beyond our capacity to influence, frankly, says Schaffner. There are huge commercial imperatives out there, whichdoesnt mean that any of us recommend it we dont. What we all recommendis good handwashing. This is particularly true in the winter respiratory season,because not only can you transmit winter respiratory viruses through closecontact (sneezing, coughing, and the like), but contaminated hands clearly havebeen shown to be a vehicle for transmission. So when you come in from theoutside, wash your hands. Obviously, wash your hands after youve used therestroom, wash your hands when you are about to prepare food or eat. Wash your hands frequently, just as your mama told you. It isnt hightech,but that doesnt mean its not highly effective.

Infection-resistant Devices

When we move into the healthcare environment and we begin to addressissues such as urinary catheters, or indwelling intravenous or intra-arterialcatheters that may be impregnated either with an antibiotic or some sort ofother antibacterial substance, there the issues are quite specific, saysSchaffner.

In July 2001, the Agency for Healthcare Research and Quality (AHRQ) publishedthe document, Making Healthcare Safer: A Critical Analysis of Patient SafetyPractices, listing the 11 most highly rated patient safety practices. No. 11on the list was Use of antibioticimpregnated central venous catheters toprevent catheter-related infections.¹

Thats a very credible government agency that really studies patientimprovement practices and outcomes, says Charles Edmiston, PhD, CIC,associate professor of surgery at the Medical College of Wisconsin and hospitalepidemiologist at Froedtert Memorial Lutheran Hospital. So there is this dataout there that strongly suggests that these devices may be beneficial,especially in high-risk patients. Most of us agree that these devices may nothave a complete universal application, but they certainly seem to warrantconsideration in high-risk patients, for example, ICU patients.

ETHICON has recently developed an antiseptic surgical suture impregnated withTriclosan. Theres an interest in looking at this type of device to reducethe incidence of selected wound infections, especially in high risk patients,says Edmiston. Triclosan is an antiseptic that disrupts cell membranes of bacteria. Itsvery safe. The thought process is that this antiseptic-impregnated device mayhave a measurable benefit in superficial incisional site infections about 40to 60 percent of the infections that we see in hospitalized infections. Weretalking about those infections that we classify as superficial incisional. Thatsthe key, because this device is not going to have any benefit for organ space,for example, for deep infection. But many of us think it will have a benefit onskin surface incision infections.

There is a wide body of interest in these antiseptic-impregnated devices,says Edmiston. The key, obviously, is safety. And there is a lot of safety data on manyof these compounds. Obviously there is a premium associated with using a devicelike this. The issue is, for most of us who look at these devices, not what isthe risk versus benefit because many of these devices have been well tested;theyre safe but benefit vs. cost. You look at the intrinsic benefit of the device versus the acquisitioncost.

All of us would like to see devices that are infection-resistant, Schaffner stresses. One can always develop a theoretical rationale for theintroduction of various presumably antibacterial substances into devices. Butwhat it comes down to is doing the prospective placebo-controlled clinicaltrials. That is of course, the sort of level of evidence that all of us wouldnot only like to see, but would be required by licensing agencies for a newpharmaceutical agent of one kind or another. But unfortunately, the requirementsfor new medical instruments are not that stringent.

But when you suddenly encounter a manufacturers sales representative inyour office, if you ask for those kind of clean data prospective controltrials they are rarely, if ever, available, says Schaffner.

Schaffnercites cost as a primary reason for the absence of prospective controlled trials.They are clearly expensive, he says. You usually need to have large numbers of patients, often a multicentertrial, the company has got to mock up the device to include placebos and realdevices; it requires the whole mechanism of doing clinical trials. Its veryexpensive and cumbersome, and of course the company as much as they are inlove with their own product is looking at a big investment with an uncertainoutcome. Suppose the results of the trial show that there isnt much benefit?All of a sudden, everything that the company has invested is at risk. Andbecause its not required by the FDA for licensure, why risk doing that? Ifyou and I were running a company and were responsible financially tostockholders, we would not put the venture at that kind of risk.

So, we have a circumstance where all of us would like to see effectiveproducts tried, but when they come to market, the level of evidence indicatingtheir effectiveness is very thin and uncertain, continues Schaffner. Thats unfortunate. And at the moment, neither theCDC nor the FDA nor the NIH would be in any way inclined to sponsor those kindsof studies, never mind industry itself. So we have a large vacuum here whichis not to say that anything is illegal, its just not as rigorous as we wouldlike and that often leaves us in a quandary.

Why dont the clinicians involved perform their own studies? Time, saysSchaffner.

If you sit down with a biostatistician and calculate how many patient daysof exposure you would have to have among current catheters vs. the newcatheters, you could see that in any reasonably sized unit, you would have to dothe study for eight years before you have enough data to have a statisticallyvalid result at which point the surgeons become sobered. They understand.And thats why we always say, Now you understand, or at least you have anappreciation why it is that we think that these sorts of studies ought to berequired pre-licensure. It would be very unusual for an individualinstitution to be able, even if they could organize the study, to get enoughinformation in a reasonable period of time to securely answer that question.

So the answer is not complete on this issue. I think a lot of us arelooking at these antiseptic-impregnated devices, seeing whether or not theresbreakthrough or development of resistance against these materials, saysEdmiston. But even though a definitive answer is not yet available, he believesthat progress is being made.

I think thats why theres an interest in these antiseptic-impregnateddevices. One thing we should always appreciate is that these devices shouldnever be considered Band-Aids. These are not devices that we are going to usebecause our technique is sloppy and this is going to replace or supplement ourpoor technique. I always view these devices as adjunctive, as devices that weuse along side and in combination with our standard infection control practices.Or if were talking about devices that have an antiseptic coating and used inpatients, these devices are adjunctive along with appropriate surgicalprophylaxis. But having said that, I really believe that some of these devicestruly have a benefit, especially in our higher-risk patient populations.