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ICT spoke with Rabih Darouiche, MD, professor and director ofthe Center for Prostheses Infection at Baylor College of Medicine, regardingstrategies for preventing catheter-associated urinary tract infections (CAUTIs).
ICT:How do you define a CAUTI,and what do you believe is the scope and magnitude of the problem?
RD: This is a tremendous problem interms of incidence, morbidity, potential mortality, as well as economicimplications. In terms of incidence, we know that indwelling urinary cathetersare responsible for almost 95 percent of all cases of nosocomial urinary tractinfections (UTIs). And we know that about 30 million bladder catheters areinserted each year in the United States alone. It is estimated that probably atotal of about 1 million cases of CAUTIs occur each year in this country. Infact, CAUTIs are the most common nosocomial infection that occurs in associationwith any type of an indwelling medical device.
In terms of medical complications, although most cases tend toinvolve only the lower urinary tract, in some populations even a minor episodeof lower UTI may affect other aspects of their healthcare. For example, if youtake hospitalized patients with spinal cord injuries who are admitted primarilyfor rehabilitation, and if such patients develop even a minor case of cystitisassociated with an indwelling bladder catheter, then that will result in downtime for rehabilitation, which means prolonged hospitalization.
Furthermore, about 5 percent to 10 percent of such cases ofCAUTIs involve the upper urinary tract, causing polynephritis; those cases arethe ones that may result in urosepsis, septicemia, and sometimes even death. Thethird impact of CAUTIs has to do with economical effects, such as prolongedhospitalization due to UTI, having to miss a number of days of work because ofillness, or having to receive antibiotics, either intravenously or orally ...these factors all combine to produce a tremendous economic impact.
ICT: What is the cost of treatinga UTI and of treating urosepsis?
RD: It depends on whether thepatient is treated in the hospital or as an outpatient. It also depends on thetype of organism(s) causing the infection. Generally, the average cost for treatment of a UTI as anoutpatient, when using oral therapy, may not exceed a few hundred dollars. Andit may even be cheaper if its caused by a multi-susceptible organism thatcould be treated by genericlabel oral antibiotics. However, because of theexcessive unnecessary use of antibiotics, most cases of CAUTI are caused byresistant organisms, which have to be treated either with expensive oral drugs,or in some cases have to be treated with parenteral antibiotics because thereare no available oral options that would provide coverage for those particularinfecting organisms. For an inpatient case, you must add the overall costs ofextended hospitalization, nursing care and parenteral antibiotics, and that isexcluding the lack of productivity for patients who lose time from work. It can be very expensive, and most estimates are in theneighborhood of $2,000 per infection.
ICT: And the cost of urosepsis?
RD: Urosepsis by definition meansthat not only do you have a UTI, but that the patient has systemic effects ofthe infection. Most cost estimates to treat are in the range of $30,000.
ICT: Clearly, we can concludethat CAUTIs are both common and costly. How do uropathogens gain access in thecatheterized patient?
RD: There are three main routes ofentry of infecting pathogens. The most commonly observed one is when theorganisms gain entrance into the urinary tract by originating from the junctionbetween the urethral meatus and the external surface of the catheter. Withprolonged catheter duration and therefore with more manipulation of the catheterby healthcare providers, then we tend to see more of the effects of the secondroute of entry, which is entry of contaminating organisms through the junctionof the catheter and the draining tube. The third route of entry, which is not ascommon as the first two routes, is when you have bacterial contamination of theurinary drainage bag, particularly in patients in whom the drainagebag is kept at a level higher than the bladder, thereby allowing collectedurine, which contains bacteria, to drain back into the bladder, therebyresulting in bacteriuria and eventually UTI.
ICT: Which organisms mostcommonly infect via these various routes?
RD: The most common organisms arethe grand negative bacteria and the Enterococci.These organisms are most common because they are components of the bowel floraand because of the proximity of the rectum to the urethral meatus; the skin andadjacent to that area is likely to be colonized by those infecting pathogens.Unlike in the case of vascular catheters where the infecting skin organisms aremostly staphylococci, in the case of CAUTIs, staphylococci only rarely causeUTIs.
ICT: We hear a lot these daysabout bacterial biofilms. Do such biofilms play a role in CAUTIs?
RD: All cases of device relatedinfections are biofilm related; the reason is because within a short period oftime after insertion of any foreign device, a combination of host factors, likefibrin, fibrinectin, fibrinogen, platelets and other host products, combine withbacterial organisms and their own products, to form the layer of mature biofilm.That layer of biofilm will form whether the catheter is inserted into theurinary system, the vascular space, the ventricular space, or any other area inthe human body.
ICT: Does the presence of aurinary drainage catheter, eventually coated as you suggest with bacterialbiofilm, always result in a bacteriuria?
RD: It depends on the type of thecatheter and the duration of catheter placement. For example, in patients withchronic indwelling of bladder catheters, the longer the duration the more likelythey will develop bacteriuria, which means just bacteria in the urine. Forexample, if you take catheters that have been in place for a week or longer, thelikelihood of having bacteriuria by then is probably about 90 percent.
ICT: Does bacteriuria represent adisease state requiring treatment?
RD: I think that is an extremelyimportant issue, which unfortunately has clouded the evaluation of measures thatcould potentially prevent CAUTIs.
Bacteriuria simply means a presence of bacteria in the urine.Most patients with an indwelling bladder catheter will have bacteriuria. Mostcases of bacteriuria will remain asymptomatic. Only a small percentage depending on the type of patient and duration of catheter placement, and perhapseven the type of organisms responsible for the bacteriuria, because some of themare more virulent than others become symptomatic. I would say anywherebetween 10 percent and 30 percent of cases of bacteriuria will become associatedwith a clinical episode of CAUTI. That is very important to comprehend becausethe primary objective in coming up with an optimal solution for CAUTI is toprevent this infection rather than to prevent bacteriuria. In fact, you may notbe able to prevent bacteriuria. Moreover, even if you decrease the incidence ofbacteriuria, there is no guarantee that that decrease in the incidence ofbacteriuria will result necessarily in the reduction in the rate of CAUTI.
ICT: The Occupational Safety andHealth Administration (OSHA) frequently refers to work-practice controls andengineering controls. Work practice controls mean primarily methods of use,measures that one can take in the course of daily practice. Engineering controlsrefer to products. Are there work practice controls habits of use, technique that can be implemented that in and of themselves can diminish the risk ofCAUTIs?
RD: In my opinion, the mostimportant work practice control for prevention of CAUTI is to avoidinappropriate catheterization and to remove the catheter when no longerclinically indicated. Unfortunately, studies have shown that we have not done very well with either of these twoissues, because still a significant portion of catheter insertions are deemedimproper, and because we as physicians often are not even aware that our ownpatients have an indwelling catheter. Even in instances where we are made awareof the existence of a bladder catheter in our own patients, we may noteffectively consider alternatives to catheterization; for example, an external condom or other voiding measures. Interms of nurses input, the most important preventive measure is to provideoptimal sterile techniques at the time of insertion, as well as duringmaintenance of the indwelling bladder catheter. Unfortunately, I think weprobably have reached a point of maximum return from optimizing those workhabits. Therefore, we get to a point where we should look for otheroptions that may augment those work habits.
ICT: Can you give us an overviewof the various technologies and engineering controls that have been applied tothe reduction and eradication of CAUTIs?
RD: By relying on what we know now,we have to admit that we cannot completely eradicate or prevent the formation ofthe biofilm around the bladder catheter. Therefore, our technologicaladvancements should be based on manipulation of the biofilm in one form oranother in an attempt to prevent that biofilm from triggering clinicalinfection. Theoretically, technology can achieve that objective via one of threeforms. The first form is to use drugs to fight bugs, and that form can beprovided in three fashions. The first fashion is via systemic administration ofanti-microbial agents in an effort to prevent recurrent bouts of symptomaticUTI. In that regard, clinical trials have shown that although systemic,long-term systemic antimicrobial prophylaxis may reduce the rate of UTI due tothat particular agent or agents, that comes at the expense of a higher rate ofinfection due to more resistant organisms. Therefore, with systemic prophylacticantibiotics, the overall rate of CAUTI is not reduced. Additionally, systemicantibiotic prophylaxis is associated with adverse drug effect and allergicreactions. Therefore, because of the relatively poor efficacy and the concernover safety and toxicity, this practice is largely abandoned.
The second vehicle by which we can use drugs to fight bugs isto administer them locally, as in application to the urethral meatus, irrigationof the bladder catheter or the bladder itself, and addition of anti-microbialagents to the urinary drainage bag. Clinical trials that have assessed all ofthese measures have produced conflicting or ineffective results.
That leaves us with the third vehicle by which drugs can beused to prevent bugs, which is the incorporation of antimicrobial agents ontothe surface of the catheter. Unlike in the case of vascular catheters wherethe catheter surface that is surrounded by relatively small numbers of bacterial colony counts and the skin surrounding the exit site ispotentially subject to strong protection by certain forms of anti-microbialcoatings in the context of bladder catheters, the results have not beensatisfactory. Particularly in the area of chronic indwelling bladder catheters,where to my knowledge there have been no prospective randomized clinical trialsthat have shown that a particular type of antimicrobial coated bladder catheterhas reduced the rate of infection not asymptomatic bacteriuria, butsymptomatic infection as compared with an controlled uncoated catheter. Evenin the context of short-term catheterization of patients for one, up to twoweeks, the clinical efficacy has been largely based on the results ofprospective, non-randomized clinical trials, be it prospective cohort, orprospective crossover studies. And therefore, the true efficacy of those coatedcatheters in preventing catheter associated urinary tract infection still needsto be determined through better-designed prospective, randomized clinicaltrials.
The second form of technologic advancement can be based onusing bugs to fight bugs. Knowing that bugs are very smart, they are more likelyto adapt to situations that may be harmful to them. Therefore, it may bereasonable to utilize that bacterial property to our advantage. For example, weall harbor organisms in our bodies that are not pathogenic, and those organismsin our mouth and in our bowels may compete with pathogens.
That constitutes a passive form of bacterial interference. So,healthcare providers may opt to use another form of bacterial interference, thatof active bacterial interference, where we intentionally introduce nonpathogensinto the human body in an effort to compete with pathogens.
We have studied this over the last 10 years and we have beenable to introduce a non-pathogenic strain of E. coli into the bladder ofpatients with spinal cord injury who have had frequent episodes of UTI. And bothin a small prospective open label clinical trial as well as in a smallprospective randomized placebo control evaluated blinded clinical trial, we wereable to demonstrate that this approach of active bacteria interference doesreduce the rate of infection. This prompted us to initiate an ongoingprospective randomized, multi-center, placebo-controlled, evaluator-blindedclinical trial sponsored by the National Institutes for Health.
The third form of technologic advancements that may affect theability of the biofilm to result in clinical infection is an innovativesecurement device, which is intended to reduce the likelihood of discordantmotion between the catheter and the human tissue thereby discouraging orblunting the migration of organisms along the catheter surface. This device mayalso reduce the likelihood of traumatizing the inner human tissues which form anatural barrier against infection. And we all know that a healthier, lesstraumatized tissue will probably be more able to resist clinical infection whenexposed to bacteria as compared to a more diseased and less healthy tissue. Aprospective randomized clinical trial has indicated that the use of a securementdevice called Statlock, in the context of inserted PICC lines, showedsignificant protection against catheter-related bloodstream infection ascompared with the control suture technique. Taking that into consideration, werecently completed a prospective, randomized, multi-center clinical trial thatassessed the efficacy of the Statlock device in preventing a UTI in spinal cordpatients with indwelling bladder catheters as compared with other traditionalsecurement measures such as using a tape, gauze, a Cath-secure, or even nosecurement. The results showed a remarkable 45 percent reduction in the rate ofCAUTI; remember, this is symptomatic infection in those whose bladder catheterswere secured by using the Statlock device.
ICT: Were the findings of thisStatlock study both clinically and statistically significant?
RD: As I have mentioned, there was a45 percent reduction in the rate of clinical catheter associated urinary tractinfection. That study, however, was not sufficiently powered to showstatistically significant differences. But the trend was very strong, and a 45 percent reduction in clinicalinfection which was the primary outcome in that study is very clinicallyrelevant. Furthermore, this is the only prospective randomized clinical trialthat has shown such a relatively high degree of protection against CAUTI withoutusing antimicrobial agents, which theoretically can have a number of potentialdrawbacks, including toxicity, allergic reactions and potential for developmentfor antibiotic resistance.
ICT: What measures then would younow take to prevent or limit CAUTIs in patients with both short-term andlong-term indwelling Foley catheters?
RD : In patients with short-termindwelling bladder catheters, I think the most effective approach would be toprevent inappropriate catheterization to start with; to become more aware of theexistence of those bladder catheters in our own patients; and then, to act uponthat information once obtained by considering an alternative to bladdercatheterization.
In patients with long-term indwelling bladder catheters, it isimportant to rely more on technological advances. In either case, I think itsimportant to consider technologic advances that have been found in prospectiverandomized clinical trials to produce clinically relevant reduction in the rateof CAUTI. In that regard, we know that the Statlock securement device has beenfound to produce a very clinically relevant reduction in the rate of infectionassociated with long term in dwelling bladder catheters. Although no studieshave been done in the context of short-term catheters, because the mechanism ofinfection is essentially the same, the use of StatLock in that population shouldbe considered as well. As far as antimicrobial-coated catheters, I am not aware ofany studies that have shown efficacy in long-term bladder catheters. Theirstudies have been largely applied to short-term bladder catheters. So althoughsuch coated catheters may be considered for use for short-term bladdercatheterization, there is no guarantee that they will be protective forlong-term bladder catheterization.
ICT: Theres a great deal ofevidence looking at the efficacy of catheter coatings. What is the greatestlimiting factor in those studies?
RD: I think the primary limitationof those studies, of the vast majority, is that they have considered the mereexistence of bacteriuria as a primary outcome. Whereas we know that the onlyimportant clinical outcome should be symptomatic UTI. And therefore if a study,even if well-designed, showed a reduction in the rate of bacteriuria, it may notnecessarily guarantee that a simultaneous reduction in the rate of clinicalCAUTI will be observed as well.