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Annu. Rev. Med. 1990.41:169-176. Downloaded from www.annualreviews.org Access provided by University of Texas Southwestern Medical Center on 01/25/15. For personal use only.

CURRENT ISSUES IN CENTRAL VENOUS CATHETER INFECTION Philip Toltzis, M.D.

Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106

Donald A. Goldmann, M.D.

The Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115 KEY WORDS:

nosocomial infection, bacteremia.

ABSTRACT

The majority of central venous line-associated infections are caused by organisms on the skin near the exit site gaining access to the intravascular segment of the catheter. A variety of strategies have been used in an effort to reduce catheter contamination, but one innovation-the semipermeable transparent dressing-may actually increase infection risk. On the other hand, new catheter materials and designs probably reduce the risk. There are only a limited number of well-designed studies of the increasingly popular totally implantable catheter system and the multilumen line, but it appears that the former is associated with a low rate of infection, while the latter may be more hazardous than the single-lumen line. INTRODUCTION

Central venous lines (CVLs) are now routinely used in contemporary medicine. These devices provide dependable vascular access in seriously ill patients who require many days of intravenous fluids, parenteral medi­ cations, and hyperalimentation. Previous comprehensive reviews have described the clinical appearance, pathogenesis, and management of CVL169 0066 -4219/90/0401-0169$02.00

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related infections (1, 2). In this chapter we concentrate on recent devel­ opments in two areas: (a) strategies for preventing microbial contamination of the catheter and (b) complications of two relatively new devices, the totally implantable catheter system and the multiple-lumen line.

STRATEGIES FOR PREVENTING MICROBIAL CONTAMINATION OF CVLs

Strategies for preventing contamination of CVLs have focused on decreas­ ing the number of microorganisms around the exit site and inhibiting their entry into the catheter wound. Of course, CVL infections may be caused by contaminated infusions, hematogenous seeding by organisms from distant sites of infection, or contamination of the catheter hub (3), but a considerable body of data suggests that contamination of the catheter by organisms on the patients's skin is far-and-away the major problem. In a mouse model of catheter infection, Cooper et al (4) showed that bacteria inoculated on the skin are rapidly transported along the track of the catheter to the catheter tip. Having entered the catheter wound, coagulase­ negative staphylococci (one of the most common CVL pathogens) express adhesins that enhance their ability to colonize catheter plastics (5). Once attached to the catheter, coagulase-negative staphylococci elaborate a biofilm ("slime") that protects them from host defenses (6). Microcolonies of staphylococci have been observed embedded in biofilm clinging to infected catheters that have been removed from patients (7), and microscopy of the exterior surface of Gram-stained catheters has even been suggested as a diagnostic test for catheter infection (8). Not sur­ prisingly, the organisms residing on the skin near the catheter exit site are frequently the same as those found on the tip of the infected catheter (9, 10). Indeed, in a febrile patient with a CVL and no apparent source of infection, skin colonization at the exit site has a 61% positive predictive value for catheter tip infection, while absence of organisms on the skin has a 98% negative predictive value (10). In those instances where the skin tests are positive but the tip is not infected, growth on the skin tends to be sparse and transient. Traditionally, procedures designed to protect the exit site fro� microbial colonization have included defatting with acetone, washing with an anti­ septic, applying an antimicrobial ointment, and using a stcrile dressing. There are few controlled data, however, documenting the relative import­ ance of these measures. Indeed, Maki and coworkers (11) demonstrated that defatting the skin has no detectable effect on the presence or density of organisms around the exit site, nor on the incidence of catheter con-

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VENOUS CATHETER INFECTION

171

tamination or CVL-related bloodstream infection. Although there is vir­ tually universal agreement regarding the importance of thorough cleansing of the skin with an effective antiseptic prior to catheter insertion, few studies have been performed to evaluate the choice of antiseptic or the need to rec1eanse the skin when the dressings are changed. It is likely that any broad-spectrum antiseptic would be adequate for this purpose. There are few data supporting the long-held practice of applying antimicrobial ointment to the catheter exit site. Two studies performed 20 years ago (12, 13) indicated that ointment containing polymyxin, bacitracin, and neomycin delayed, but did not prevent, contamination of peripheral venous cannulae. - At best, the efficacy of antimicrobial ointment is marginal, and other factors, such as adminstration of systemic antibiotics and adequate sterile technique, may be more important (12-14). There is increasing evidence that the incidence of catheter colonization and infection is influenced by the type of dressings applied to the exit site. In recent years, semipermeable transparent dressings have achieved wide popularity because, unlike gauze, they permit inspection of the exit site without removing the dressing_ Although considerably more expensive than gauze, the increased cost of transparent dressings was thought to be offset by savings in personnel time required for frequent changes of gauze dressings. Initial small, noncomparative trials (15, 16) suggested that trans­ parent dressings could be changed safely once a week if the exit site remained noninflamed. However, subsequent trials have revealed that transparent dressings lead to significantly heavier microbial growth on the underlying skin, which in turn is associated with an increased risk of catheter contamination (17-20). For example, in one comprehensive ran­ domized trial (20), 7 of 42 patients (16.6%) with transparent dressings experienced catheter sepsis, compared to 0 of 34 patients with gauze dressings (P 0. 015). To some extent these alarming results may be attributable to the fact that the transparent dressing remained in situ for longer periods than gauze dressings. However, if transparent dressings have to be changed more frequently to reduce the infection risk, much of their convenience would be negated, and their expense would no longer be justifiable. Several changes in the design and composition of the catheters them­ selves may have resulted in a decreased incidence of CVL contamination and sepsis. It has long been recognized, for example, that pliable materials, such as polytetrafluoroethyiene (Teflon®) and silicon elastomer (Silastic®), are less likely to be associated with phlebitis, thrombosis, and infection than the rigid plastics used in the past. Some investigators have suggested that additional resistance to infection could be achieved by impregnating these catheter materials with antimicrobials. Noncovalent bonding of anti=

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biotics to plastic catheters has resulted in a lower rate of catheter con­ tamination in laboratory animals (21), but this approach clearly is still experimental. On the other hand, a silver-impregnated collagen cuff that can be attached to percutaneously placed CVLs has already reached the marketplace (Vitacuff®, Vitaphore Corporation, San Carlos, California). This cuff not only forms a physical barrier to skin organisms, similar to the Dacron® cuffs of Broviac and Hickman silicon elastomer lines, but also provides an antimicrobial barrier, based upon the broad-spectrum activity of silver. In a multicenter study, Maki and colleagues (22) ran­ domized 234 patients to receive cuffed or noncuffed CVLs. A significant reduction in catheter colonization and local infection was noted in the group with cuffed catheters, particularly after four days of placement. Five control catheters (3.7%) were associated with bacteremia, compared to one cuffed catheter (1.0%, P 0.12). In a second randomized controlled trial, Flowers et al (23) found that catheter colonization occurred sig­ nificanly less frequently with the silver-impregnated cuff than without it (7. 7 vs 34.5%). No catheter-related bacteremias occurred in the 26 patients with cuffed catheters, whereas there were four bacteremias among 29 control catheters (13. 8%). In both the Maki and Flowers studies, a small percentage of cuffs extruded from the exit site prior to removal; under these circumstances, the incidence of catheter infection was equal to that seen in uncuffed lines (22). =

IMPLANTABLE AND MULTILUMEN CATHETERS

Over the past several years two new catheter sytems have become extremely popular. The totally implantable catheter system has been used as an alternative to the externalized tunnelled silicon elastomer line in patients who require prolonged intravenous access. Multilumen catheters have been used primarily in intensive care unit patients who require relatively short-term percutaneous catherization for concurrent diagnostic and therapeutic interventions. Totally Implantable Catheter Systems

Implantable catheter systems require minimal maintenance and are barely noticeable to the casual observer. Several brands are currently available, differing primarily in the diameter of the catheter and the construction of the reservoir port. All of the systems have an injection reservoir constructed from stainless steel or plastic, which is surgically implanted into a sub­ cutaneous pouch in the thoracic wall and anchored by sutures placed through fixation rings. To the port is attached a silicon elastomer catheter; like a conventional silicon elastomer CVL, it is tunnelled subcutaneously

173

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VENOUS CATHETER INFECTION

into a large vessel. The injection port itself is entered by inserting a side­ opening Huber needle through the skin and into the reservoir through a silicon rubber septum. Up to 1500 entries are possible without septum leakage. The needle may be bent 90 degrees and attached to the chest wall to provide access for days of continuous infusion (24, 25). Table I summarizes the experience with implantable systems represented by ten published studies. Mechanical complications were noted in all of these reports, occurring in approximately 10-25% of catheters inserted­ a rate comparable to that seen with externalized lines (26). These com­ plications included catheter occlusions [about half of which were suc­ cessfully treated in situ with injection of streptokinase, anti-coagulation, or both (25, 27, 28)], catheter tip migration into the jugular vein, and extravasation of infusate into the subcutaneous pocket. This last com­ plication resulted from slippage of the needle out of the reservoir. Usually such slippagc is of little conscquence, but extravasation of caustic fluids, such as some chemotherapeutic agents, may cause necrosis of the skin and

subcutaneous tissue, and necessitates removal of the system. The skin theoretically should provide a natural barrier to contamination of the implantable system with cutaneous organisms, and thus reduce the risk of infection. Infections of the subcutaneous pocket, the catheter tip, or both still occur, but the infection rate of implantable devices has been rather low, ranging from 0 to 0.10 per 100 patient-days, with several invcstigators reporting ratcs as low as 0.04-0.06 per 100 paticnt-days (26,

Table 1

Cumulative experience with totally implantable cathetersa Infection/ Catheters

Pocket

CVL-

100

sepsis

patient-days

0 (0)

0.00

(1)

0.10

Reference

(No.)

24

20

5(25)

0(0)

o (0)

25

75

4 (5)

3 (4)

6

26

50

I (2)

2 (4)

7(14)

0 (0)

0.06

27

92

15 (16)

6(6)

6 (6)

2 (2)

0.02

4 (1)

0.03

a

Occlusion

Extravasation infection

(8)

I

28

329

30 (9)

21(6)

32

29

16

2(12)

I (6)

0

30

39

7(17)

0(0)

31

31

4 (13)

0(0)

I (3)

4(13)

0.05

32

35

1 (3)

1(3)

0 (0)

0.00

33

32

7

I (3)

0 (0)

o (0) o (0)

(21)

(15)

2(12)

3 (7)b

0.05 0.04

0.00

Numbers expressed as total number of patients affected, with percentage affected in

parentheses. b Includes

both pocket infection and sepsis.

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174

TOLTZIS & GOLDMANN

29-31). This is about one third the rate generally reported for externalized lines. Only one study has prospectively compared concurrent experience with externalized and implantable lines (26). With externalized lines, there were 0.13 exit-site infections per 100 catheter-days and 0.03 episodes of bacteremia per 100 catheter-days. In contrast, with implanted devices, there were 0.06 pocket infections per 100 catheter-days, and bacteremia did not occur at all (26). Estimation of the success rate of in situ antibiotic therapy is precluded by the small numbers of reported cases, but we have been forced to remove a number of infected devices because of our inability to sterilize the contaminated reservoir. Multilumen Catheters

Multilumen catheters (MLCs) were introduced in the early 1980s to accom­ modate the increasing complexity of intensive care. They are composed of a bundle of two or three catheters of differing diameter that are infused through separate ports. This design permits the concomitant admin­ istration ofTPN, fluids, and medications, often along with monitoring of central pressure. Despite the obvious convenience of MLCs, there has been considerable concern regarding their s afety. Since these lines are designed to serve multiple purposes, they are manipulated by staff more frequently than single-lumen catheters, which increases the risk of contamination (34). In addition, their wide external diameter requires a larger wound, possibly potentiating exit-site infection (34). Numerous studies have examined the infection rate of MLCs. Unfor­ tunately, although most s tudies have been prospective, some (35, 37, 38) have not been comparative, and only one (38) has been randomized. Given these caveats, the majority of investigators report that the risk of infection is greater with MLCs than with single-lumen lines. Although rates of MLC-related sepsis have been as low as 3-5% at some centers (35, 36, 39), others (34, 37, 40, 41) have experienced a 3-5-fold higher total infection rate with MLCs compared to single-lumen lines. In addition, infectious complications of MLCs appear sooner after placement than those affecting single-lumen devices (34, 40). Data from the one prospective randomized study (38) are representative: 36 patients with a single-lumen catheter were compared to 39 patients receiving a triple lumen line. Patients with triple­ lumen lines had a higher incidence of exit-site inflammation than patients with single-lumen catheters (78 vs 33% for catheters in place more than five days), a higher rate of catheter tip culture positivity (12.8 vs 0%), and a higher incidence of bacteremia (18 vs 2. 8%). Several investigators postulate that MLCs are preferentially placed in sicker patients who require multiple infusions and close monitoring. Such patients may be especially prone to catheter-related infections because of

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VENOUS CATHETER INFECTION

175

the severity of their underlying diseases (34, 40). Indeed, one non­ randomized study revealed that, although catheter-related infection was more frequent in patients with MLCs, these patients also had more surgical procedures, had spent more time in the intensive care unit, and had greater mortality than patients with single-lumen catheters (40). On the other hand, it is precisely this critically ill population that is likely to be the most adversely affected by catheter-related sepsis, and two single-lumen lines may be the safer alternative to the multilumen device in such patients (40). Literature Cited 1. Press, O. W., Ramsey, P. G., Larson, E. 8.. et al. 1984. Hickman catheter infec­ tions in patients with malignancies. Medicine 63: 189-200 2. Maki, D. G. 1983. Infections associated with intravascular lines. In Current Clinical Topics in Infectious Diseases, ed. J. S. Remington, M. N. Swartz, pp. 30963. New York: McGraw-Hill 3. Linares, J., Sitges-Serra, A., Garau, J., et al. 1985. Pathogenesis of catheter sep­ sis: a prospective study with quantitative and semiquantitative cultures of cath­ eter hub and segments. J. Clin. Micro­ bial. 21: 357-60 4. Cooper, G. L., Schiller, A. L., Hopkins, C. C. 1988. Possible role of capillary action in pathogenesis of experimental catheter-associated dermal tunnel infec­ tions. J. Clin. Microbiol. 26: 8-12 5. Tojo, M., Yamashita, N., Goldmann, D. A., et al. 1988. Isolation and char­ acterization of a capsular polysaccharide adhesin from Staphylococcus epider­ midis. J. Infect. Dis. 57: 713-22 6. Christensen G. D., Simpson, W. A., Bisno, A. L., et al. 1982. Adherence of slime-producing strains of Staphylococ­ cus epidermidis to smooth surfaces. In­ fect. Immun. 37: 3 18-26 7. Peters, A., Locci, R., Pulverer, G. 1988. Microbial colonization of prosthetic de­ vices. II. Scanning electron microscopy of naturally infected intravenous cathe­ ters. Zentralbl. Bakteriol. Miksobiol. Hyg. B 173: 293-99 8. Cooper, G. L., Hopkins, C. C. 1985. Rapid diagnosis of intravacular cathet­ er-associated infection by direct Gram staining of catheter segments. N. Engl. J. Med. 312: 1142-47 9. Sitzmann, J. V., Townsend, T. R., Siler, M. C., et al. 1985. Septic and technical complications of central venous cathe­ terization. Ann. Surg. 202: 766-70 10. Snydman, D. R., Pober, 8. R., Murray,

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S. A., et al. 1982. Predictive value of surveillance skin cultures in total par­ enteral nutrition related infection. Lan­ cet 2: 1385-88 Maki, D. G., McCormack, K. N. 1987. Defatting catheter insertion sites in total parenteral nutrition is of no value as an infection control measure. Am. J. Med. 83: 833-40 Norden, C. 1969. Application of anti­ biotic ointment to the site of venous catherization-a controlled trial. J. Infect. Dis. 120: 611-15 Zinner, S. H., Denny-Brown, B. c., Braun, P., et al. 1969. Risk of infection with intravenous indwelling catheters: effect of application of antihiotic oint­ ment. J. Infect. Dis. 120: 616-19 Maki, D. G., Band, J. D. 1981. A com­ parative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection. Am. J. Med. 70: 739-44 Palidar, P. J., Simonowitz, D. A., Ore­ skovich, M. R., et al. 1982. Use of op site as an occlusive dressing for total par­ entcral nutrition catheters. J. Parenteral Enteral Nutr. 6: 150-51 Vazquez, R., Jarrard, M. M. 1984. Care of the central venous eatherization site: the use of a transparent polyurethane film. J. Parenteral Enteral Nutr. 8: 18186 Powell, c., Regan, c., Fabri, P. J., et al. 1982. Evaluation of Opsite catheter dressings for parenteral nutrition: a pro­ spective, randomized study. J. Par­ enteral Enteral Nutr. 6: 43-46 Kelsey, M. c., Gosling, M. 1984. A com­ parison of the morbidity associated with occlusive and nonocclusive dressings applied to peripheral intravenous de­ vices. J. Hasp. Inject. 5: 313-21 Andersen, P. T., Herlevsen, P., Schaum­ burg, H. 1986. A comparitive study of 'op site' and 'nobecutan gauze' dressings

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for central venous line care. J. Hosp. Infect. 7: 161-68 Conly, J. M., Grieves, K., Peters, B. 1989. A prospective randomized study comparing transparent and dry gauze dressings for central venous catheters. J. Infect. Dis. 159: 310-19 Trooskin, S. Z., Donetz, A. P., Harvey, R. A., et al. 1985. Prevention of catheter sepsis by antibiotic bonding. Surgery 97: 547-51 Maki, D. G., Cobb, L., Garman, J. K., et al. 1988. An attachable silver-impreg­ nated cuff for prevention of infection with central venous catheters: a pro­ spective randomized multicenter trial. Am. 1. Med. 85: 307-14 Flowers, R. H. III, Schwenzer, K. J., Kopel, R. F., et al. 1n9. Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter­ related infection. J. Am. Med. Assoc. 261: 878-83 Gyves, J., Ensminger, W., Niederhuber, J., et al. 1982. Totally implanted system for intravenous chemotherapy in pati­ ents with cancer. Am. J. Med. 73: 841 45

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Current issues in central venous catheter infection.

The majority of central venous line-associated infections are caused by organisms on the skin near the exit site gaining access to the intravascular s...
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