Catheter-Related Infections and How to Prevent Them
Abstract & commentary
Synopsis: Instillation of vancomycin and heparin into a central venous catheter prevented endolumenal catheter-related infection due to gram-positive bacteria in neutropenic patients with hematological malignancies.
Source: Carratal J, et al. Randomized, double-blind trial of an antibiotic-lock technique for prevention of gram-positive central venous catheter-related infection in neutropenic patients with cancer. Antimicrob Agents Chemother 1999;43:2200-2204.
Fifty-seven patients with nontunneled, multilumen, central-venous catheters (CVCs) were assigned at random to receive in their lumens 10 U/mL of heparin and 60 patients were assigned to receive 10 U/mL of heparin and 25 mcg/mL of vancomycin. The drugs were instilled every two days and were allowed to remain for one hour to create a "lock" before being removed. Insertion site and hub swabs were taken twice weekly and blood cultures were obtained at the onset of fever before systemic antibiotic therapy was begun.
Significant colonization of the catheter hub occurred in nine (15.8%) patients receiving heparin alone (7 patients with Staphylococcus epidermidis and 1 patient each with S. capitis and Corynebacterium species), whereas none of the catheter hubs in patients receiving heparin and vancomycin was colonized (P = 0.001). Catheter-related bacteremia developed in four (7%) patients given heparin alone (3 patients with S. epidermidis and 1 with S. capitis), whereas none of the patients given heparin and vancomycin was affected (P = 0.05). Heparin and vancomycin delayed the time to catheter hub colonization and to catheter-related bacteremia relative to heparin alone (P = 0.004 and P = 0.06, respectively). Thus, creating an antibiotic lock using a solution containing heparin and vancomycin administered as an antibiotic lock prevented catheter hub colonization with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients with hematological malignancy.
Comment by j. peter donnelly, phd
This is a nice little study which, at first glance, appears to offer a relatively simple and effective means of preventing the all too common problem of CVC colonization and infection. However, on closer reading, some curious omissions become apparent. First, catheter-related infection (CRI) was defined as the isolation of the same organism from both the catheter hub and blood cultures. This does not invalidate the conclusion that vancomycin and heparin reduce hub colonization but there are good reasons for questioning the apparent efficacy of this approach in preventing catheter-related bacteremia, let alone the other types of CVC-related infections, because the definition was too narrowly defined. Not only were 33 patients (61.1%) who were given heparin alone and 35 (58.3%) patients given heparin and vancomycin given vancomycin therapeutically but 13 and 15 patients, respectively, had bacteremia. We are not told the identity of these isolates, only that none was attributable to catheter infection, nor are we told the fate of the patients involved but more likely than not they were treated with vancomycin. Given the patient population, my guess is that many, if not most, of these were also due to coagulase-negative staphylococci similar to the ones implicated in the CRIs reported.
Also, blood was not drawn through the lumens of the catheters for culture at any time via the catheter, although, had such cultures been done, there would almost certainly have been more CRIs than stated. There were also no results of catheter tip cultures so we don’t know if any were colonized according to the criteria of Maki and colleagues.1 These criticisms may seem trifling, even nugatory, but they actually illustrate the difficulties confronting those investigating the complications associated with these devices. From a practical perspective, being able to navigate patients through neutropenia without having to treat them with vancomycin for CRIs of any description would be considered a successful outcome. Neither approach differed in this respect since 19 cases (35.2%) for heparin alone and 22 cases (36.7%) for heparin plus vancomycin were successfully managed. The incidence of occlusion was also not different being six (10.5%) and four (6.7%), respectively, and although there were slightly more episodes of bacteremia in the heparin-only group (see above), this did not translate into a difference in vancomycin usage for therapy, which was the same, and high, in both groups. Thus, the clinicians must weigh the reduction in hub colonization against these other considerations but will most likely decide either to adopt the approach because it may do some good and little harm or to reject the approach because there is no real benefit.
There are already some 850,000 cases of CRI reported annually in the United States alone, of which at least 50,000 involved bacteremia.2 Managing these infections is, therefore, not a trivial issue. Yet, despite all this, there seems little real enthusiasm for tackling the problem thoroughly. Moreover, there are too many schools of thought to define the complications. Simply put, infections arise from inside the catheter, be it hub or intralumenal colonization, or from outside the device, extra-lumenal, and each requires different techniques to identify them. The most widely used method of determining catheter colonization is to roll 2-3 inches of the device over an agar plate and count the resulting colonies that result after one or two days of incubation (the Maki roll-plate technique). This will tell you, after the fact, if the device is colonized, if there has been bacteremia or isolates from other infective focus, and if they originated from the outside of the catheter. The technique provides no information whatsoever on intralumenal colonization. By contrast, drawing blood through the catheter every three or four days routinely, even in the absence of fever, makes it possible to determine intralumenal colonization. An alternative elegant technique is to culture the heparin-lock fluid daily since this yields a positive predictive value of 100% for bacteremia.3 More elegant still is to use a tiny brush, which is more sensitive (95%) and specific (84%), in diagnosing CRI than extralumenal sampling of the catheter tip by the Maki roll technique (82% and 66%, respectively). Identifying intralumenal colonization provides a choice of trying to save the catheter or remove it.4 But because there is a bewildering assortment of central vascular devices available and increasingly ones with two and three lumens are being used, identifying colonization becomes automatically more expensive because more samples need to be processed. Moreover, the variable nature of the most common colonizer, S. epidermidis, demands more work in fingerprinting the isolates. Naturally, microbiologists require funds for this extra work but no one is queuing up to provide them. Instead, more and more people are looking toward the antibiotic option and instilling these drugs into their catheters because it seems to be the cheaper option. Meanwhile, the pressure is growing to reduce antibiotic use to avoid resistance and augment their lifespan. Fertile ground if ever there was some for a comprehensive study of the epidemiology of CRI to identify risk factors that can be modified safely, effectively, and economically. The laboratories have the techniques and there are a variety of interventions that could be considered. Judging by the number of publications on this issue (some 27 this year so far) there is still plenty of interest. I, like many, normally eschew large corporate enterprises preferring to do things on a smaller local scale, but I might be prepared to make an exception in this case if more comprehensive definitions are used. I will read my e-mails more assiduously in the coming months to see if anyone else feels the same.
References
1. Maki DG, et al. A semiquantitative culture method for identifying intravenous catheter-related infection. N Engl J Med 1977;296:1305-1309.
2. Elliot T. Role of antimicrobial central venous catheters for the prevention of associated infections. J Antimicrob Chemother 1999;43:441-446.
3. Guiot HFL, et al. The relevance of cultures of catheter-drawn blood and heparin-lock fluid to diagnose infection in hematologic patients. Ann Hematol 1992;64: 28-34.
4. Kite P, et al. Evaluation of a novel endolumenal brush method for in situ diagnosis of catheter-related sepsis. J Clin Pathol 1997;50:278-282.
Instillation of small amounts of heparin and vancomycin into central venous catheters, when compared to instillation of heparin alone, is associated with:
a. a lesser risk of Candida bacteremia.
b. a lesser risk of bacteremia.
c. a lesser risk of catheter hub bacterial colonization.
d. a lesser risk of catheter occlusion.
Bacterial colonization of intravenous catheters may be:
a. intralumenal.
b. inside the catheter hub.
c. extralumenal.
d. All of the above
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