Single-lumen central venous catheters were introduced in the 1970s. In the 1980s, dual-lumen, tunneled, cuffed catheters were developed and became an accepted form of temporary and permanent vascular access in patients who lack other options [1]. With increasing numbers of debilitated patients undergoing dialysis, the use of dual-lumen cuffed catheters has become more common. These catheters are used for vascular access in 15% of patients undergoing dialysis in the United States [2].

Complications of vascular access devices are a major cause of illness and death in patients undergoing hemodialysis [3]. Treatment of the two major complications, thrombosis and catheter-related bacteremia, can necessitate removal of the catheter. Techniques developed in recent years have dramatically decreased the rate of catheter failure from thrombosis [4]. Infection, therefore, remains the leading cause of catheter loss. Previous studies have shown that the incidence of bacteremia is higher among patients in whom dialysis is done with noncuffed temporary catheters than among those in whom dialysis is done with cuffed, tunneled catheters [5-15]. However, the true incidence of bacteremia associated with dual-lumen, tunneled, cuffed catheters is unknown: No large prospective studies have been done, and smaller studies have not reported rates of bacteremia by using the recommended denominator of catheter-days.

The appropriate management of catheter-related bacteremia in patients undergoing dialysis has also not been clearly defined. Although clinicians generally agree about the need for intravenous antibiotics in patients with catheter-related bacteremia, they disagree about the need for catheter removal. Because many patients undergoing long-term hemodialysis have exhausted all other options for vascular access by the time a tunneled, cuffed catheter is placed, it often seems preferable to treat catheter-related bacteremia without removing the device. The results of several recent small or retrospective studies suggest that many episodes of bacteremia can be successfully treated with the catheter in place (catheter salvage), although success rates have varied. In a prospective study of 13 episodes of catheter-related bacteremia [16], use of antibiotics both systemically and locked into the catheter had a 100% success rate. In contrast, two larger studies [13, 17] found that only 25% to 31% of episodes of catheter-related bacteremia could be successfully treated with systemic antibiotics alone. Many nephrologists allow 24 to 72 hours for a salvage attempt before removing an colonized catheter, provided that there is no evidence of tunnel infection or hemodynamic compromise. The safety and efficacy of this practice is not known because no large prospective studies have examined the outcome of bacteremia in patients undergoing hemodialysis in whom catheter salvage was attempted.

To determine the incidence and outcome of catheter-related bacteremia, we conducted a prospective, observational study of outpatients undergoing hemodialysis at four dialysis centers. We also assessed the outcome of various methods of managing catheter-related bacteremia, especially attempted catheter salvage.

Methods

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We enrolled patients who underwent hemodialysis with tunneled, cuffed catheters at four dialysis centers affiliated with Duke University Medical Center between April 1995 and January 1996. Catheters were inserted in the operating room (Perm-Caths, Quinton Instruments, Seattle, Washington) or by vascular radiologists (Tessio catheters, Med-Comp, Inc., Hadeville, Pennsylvania).

For each patient, we collected demographic data and clinical information (number of years undergoing hemodialysis, history of bacteremia, and underlying medical conditions) by reviewing inpatient and outpatient charts. Patients suspected of having catheter-related bacteremia were reported to one of the authors within 24 hours of admission to the inpatient service; this author had daily contact with inpatient consulting nephrologists. Patients with bacteremia who were not admitted to the hospital were identified through interviews with dialysis personnel and through regular review of culture results from each dialysis center. The clinical response to treatment and all complications (infective endocarditis, osteomyelitis, septic arthritis, and death) were recorded for each patient. All patients with bacteremia were followed for at least 3 months after the initial episode. Patients were considered immunocompromised if they had HIV infection; cancer; or dependence on steroid treatment for systemic lupus erythematosus, chronic transplant rejection, or pulmonary disease.

We defined suspected catheter-related bacteremia as fever (body temperature >38 °C) or nonspecific systemic symptoms in a patient with a dual-lumen, tunneled, cuffed catheter for whom no other source of infection was apparent after a complete history was taken and a complete physical examination was done. We defined confirmed catheter-related bacteremia as growth of the same organism in blood cultures taken from two peripheral locations or from the catheter and a peripheral site.

We provided treatment guidelines to all clinicians caring for patients. These guidelines recommended prompt removal of the catheter in patients who developed clinical signs of sepsis, tunnel infection, or persistent fever (>72 hours' duration) or bacteremia during antibiotic therapy. Clinical management of each patient, including the choice of antibiotic and the decision to keep or remove the catheter, was determined by the attending nephrologist. Vancomycin (loading dose, 20 mg/kg of body weight) and gentamicin (loading dose, 2 mg/kg) were the antibiotics most commonly used for empirical treatment. We defined short-course antibiotic therapy as antibiotic therapy lasting 2 weeks or less, and we defined long-course antibiotic therapy as antibiotic therapy lasting more than 2 weeks. Other antibiotics were sometimes used when results of culture and susceptibility testing became available. Blood cultures were repeated 1 to 2 weeks after the initial bacteremic episode, 1 week after completion of antibiotic therapy, and when clinically indicated.

Patients with catheter-related bacteremia whose catheters were still in place 3 days after initial clinical recognition of bacteremia were considered to have had attempted salvage. Salvage was considered successful if the catheter that was in place at the time of the episode of catheter-related bacteremia was still in place at the end of 3 months or if the catheter had been removed for a reason other than persistent or recurrent bacteremia caused by the same organism (for example, if the catheter was no longer medically necessary because of maturation of alternate vascular access). Patients whose catheters were removed because of persistent fever or recurrent bacteremia caused by the same organism that was originally identified were considered to have had salvage failure. Patients who had their catheters removed in the setting of an infection caused by a new organism were excluded from the analysis.

Data analysis (relative risks and 95% CIs) was performed by using Epi Info software (USD, Inc., Stone Mountain, Georgia). Patient characteristics potentially associated with rates of infection (age; duration of hemodialysis; history of bacteremia; presence of a Gore-Tex graft, diabetes mellitus, or HIV infection; injection drug use; and immunocompromised status) and rates of infection were evaluated by using chi-square analysis. Data from the four hemodialysis centers were analyzed both separately and together, with similar results; thus, we present results from analysis of all patients in all centers. All reported P values are two tailed.

Results

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During the 9-month study period, 102 patients had dual-lumen, cuffed, tunneled catheters in place for 16 081 catheter-days. Fifty-five patients (54%) were female. Median age was 56 years (range, 24 to 87 years), and median duration of hemodialysis before the study was 2 years (range, 1 to 18 years). Twenty-three patients (23%) had conditions that met our case definition of immunocompromised status. Of these patients, 5 were infected with HIV, 3 had cancer, and 15 had long-term dependence on steroids. Forty-eight patients (47%) had diabetes mellitus, 77 (75%) had hypertension, and 6 (6%) used injection drugs on an ongoing basis.

Forty-one patients (40%) developed 62 episodes of bacteremia. The incidence of catheter-related bacteremia was 3.9 episodes per 1000 catheter-days (95% CI, 3.0 to 4.9 episodes per 1000 catheter-days). Among the four hemodialysis units, the incidence of catheter-related bacteremia ranged from 2.2 episodes per 1000 catheter-days (CI, 0.4 to 3.2 episodes per 1000 catheter-days) to 5.5 episodes per 1000 catheter-days (CI, 2.3 to 6.6 episodes per 1000 catheter-days). Episodes of bacteremia did not cluster temporally at any hemodialysis center during the study period.

Microbiology

Thirty-nine (63%) of the 62 confirmed episodes of bacteremia were caused by a gram-positive coccus, 15 (24%) were caused by a gram-negative rod, and 1 (2%) was caused by a gram-positive rod. Seven episodes (11%) were caused by more than one organism. The most commonly isolated organism was Staphylococcus aureus (Table 1).

Risk Factors for Catheter-Related Bacteremia

Table 2 shows the association between patient characteristics and the first episode of catheter-related bacteremia during the study period. After testing multiple factors (age, duration of hemodialysis, immunocompromised status, history of bacteremia, injection drug use, and presence of diabetes mellitus), we found that the risk for bacteremia was higher in patients who had a history of bacteremia (relative risk, 1.9 [CI, 1.2 to 2.9]) and in patients who were immunocompromised (relative risk, 1.6 [CI, 1.0 to 2.5]). Controlling for history of bacteremia did not affect the increased risk (relative risk, 1.6 [CI, 1.1 to 2.3]). Similarly, controlling for immunocompromised status did not affect the increased risk seen in patients who had a history of bacteremia (relative risk, 1.8 [CI, 1.2 to 2.8]).

Treatment and Clinical Outcome

Forty-eight (77%) of the 62 episodes of catheter-related bacteremia were treated with a long course of antibiotics and 14 (23%) episodes were treated with a short course of antibiotics. Thirty-six (90%) of the 40 episodes of bacteremia caused by gram-positive organisms were treated with a long course of antibiotics compared with 11 (61%) of the 18 episodes of bacteremia caused by gram-negative organisms (P = 0.02). Duration of antibiotic therapy did not differ between patients with catheter-related bacteremia whose catheters were removed immediately and patients for whom salvage was attempted.

In 24 of the 62 episodes of catheter-related bacteremia, catheters were removed within 3 days of onset. Catheter salvage was attempted in 38 episodes (Figure 1). Patients who had salvage attempted and those who had immediate catheter removal were similar with respect to age; duration of hemodialysis; sex; organism isolated; immunocompromised status; presence of hypertension, diabetes mellitus, and HIV infection; and use of injection drugs.

View larger version (21K): [in this window] [in a new window]   Figure 1. Diagram of salvage success. Patients underwent dialysis with dual-lumen, tunneled, cuffed cathete's between April 1995 and January 1996.

Treatment failed in 26 instances (68%) of attempted catheter salvage. In the patients in whom treatment failed, catheter removal was ultimately necessary because they showed evidence of persistent infection (18 patients had repeated blood cultures with growth of the initial organism, and 8 patients had continued fever with negative blood cultures). Of the remaining 12 catheters for which salvage was attempted, 2 were removed because of a new bacteremic episode, 2 were removed by the patient, and 2 were removed because vascular access was no longer needed. Only 6 catheters (16%) were in place at the end of the 3-month follow-up period. Thirty-four percent of the catheters were removed during the first month after the initial bacteremic episode; an additional 16% were removed 1 to 3 months after the initial episode.

The presence of hypertension or diabetes mellitus, injection drug use, and immunocompromised status were not associated with the likelihood of successful salvage. Fewer catheter salvage attempts were successful in episodes of catheter-related bacteremia caused by gram-positive cocci than in episodes of catheter-related bacteremia caused by gram-negative rods (6 [23%] of 26 episodes compared with 6 [50%] of 12 episodes; P = 0.14).

Nine (22%) of the 41 patients with bacteremic episodes had complications: Six developed osteomyelitis, 1 developed septic arthritis, 4 had infective endocarditis, and 2 died. The deaths occurred in patients with persistent S. aureus bacteremia and metastatic complications. All complications occurred in patients who had bacteremia caused by gram-positive organisms. No factors (diabetes mellitus, hypertension, injection drug use, or immunocompromised status) predisposed patients to the development of complications. Patients who had attempted salvage did not have an increased risk for complications: These adverse effects occurred in 5 (13%) of 38 patients who had attempted salvage and 4 (17%) of 24 patients who had their catheters removed immediately (relative risk, 0.8 [CI, 0.2 to 2.7]). The incidence of recurrent bacteremia due to the initial organism was higher in the 38 patients who had attempted salvage than in the 24 patients with catheter-related bacteremia who had their catheters immediately removed (68% compared with 17%; relative risk, 4.1 [CI, 1.6 to 10.3]).

Discussion

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Our results show that catheter-related bacteremia frequently occurs in outpatients undergoing hemodialysis. Forty percent of our patients developed at least one episode of catheter-related bacteremia during a 9-month study period. Attempts to treat patients who have bacteremia without removal of the vascular access device usually fail. Metastatic complications often occur after catheter-related bacteremia caused by gram-positive organisms, but they do not seem to be associated with attempted salvage of the device.

In our study, the incidence of bacteremia in outpatients undergoing hemodialysis with dual-lumen, tunneled, cuffed catheters was 3.9 episodes per 1000 catheter-days (CI, 3.0 to 4.9 episodes per 1000 catheter-days). This result is similar to findings in previous studies [5-10], in which rates of bacteremia in patients undergoing hemodialysis with nontunneled, noncuffed catheters ranged from 1.6 to 8.6 episodes per 1000 catheter-days. Although catheter-related bacteremia is thought to occur less frequently in patients with tunneled, cuffed catheters, the incidences reported in previous studies are applicable only to catheters that are used for temporary hemodialysis and to catheters that are maintained by use of special aseptic programs. Schwab and co-workers [11] reported a low incidence of bacteremia (1 episode per 80 catheters) associated with tunneled, cuffed catheters used for a mean duration of 8 weeks. Similarly, Queiros and colleagues [15] reported an incidence of 7 episodes of bacteremia per 103 catheters used for temporary hemodialysis. Rates of infection in two other studies were surprisingly low (1 episode per 66 catheter-months [12] and 0 episodes per 37 catheters [14]); however, both studies were designed to examine rates of infectious complications by using special programs for the aseptic maintenance of catheters. Because routine catheter care was used for all of our patients undergoing both temporary and permanent hemodialysis, we believe that the incidence of catheter-related bacteremia in our study probably represents the incidence of catheter-related bacteremia associated with outpatient hemodialysis in daily practice.

We and others [18] found that the risk for developing catheter-related bacteremia was increased in immunocompromised patients. Further study to determine which subgroups of immunocompromised patients are at increased risk may be of value. In addition, we found that patients with previous episodes of bacteremia had an increased risk for subsequent episodes of catheter-related bacteremia. It is possible that a history of bacteremia is a marker for another risk factor, such as iron overload or staphylococcal skin colonization, which in turn has been associated with an increased risk for catheter-related bacteremia [7, 12].

Our study is larger than most previous studies and is the first to examine whether catheter-related bacteremia in patients undergoing hemodialysis can be treated successfully by using systemic antibiotic therapy with the catheter in place. Our results suggest that the likelihood of successful treatment of catheter-related bacteremia is low if the catheter is not removed. The high failure rate that we observed for treatment of cases of gram-positive catheter-related bacteremia is important because gram-positive organisms were the most common cause of bacteremia [9-11, 17].

Metastatic complications of catheter-related bacteremia were frequent in our study. These complications occurred in 23% of the patients with catheter-related bacteremia caused by gram-positive organisms and in 41% of the patients with catheter-related bacteremia caused by S. aureus. This high rate of complications is consistent with findings of previous studies [19, 20] showing that catheter-related sepsis caused by S. aureus is frequently accompanied by the seeding of articular surfaces, bone, and heart valves. Surprisingly, attempted catheter salvage did not seem to increase the risk for subsequent complications. This suggests that the development of complications may not depend on the length of time that the catheter remains in place during antibiotic therapy. Alternatively, this observation may reflect a bias: Patients with less severe illness may have been initially selected for attempted catheter salvage.

These results are important for clinicians who care for patients undergoing hemodialysis. Although our findings may be generalizable to other outpatients in whom similar catheters are used (such as patients receiving chemotherapy, total parenteral nutrition, or antibiotics), underlying disease may lead to differences in salvage rates and rates of complications. In addition, we did not study antibiotic- or silver-impregnated devices, which have been reported to decrease the incidence of bacteremia, or the "antibiotic lock" technique, which has been reported to increase salvage success [16, 21, 22]. Therefore, it is important that clinicians use caution when generalizing our results to other clinical situations.

Our study was limited by its observational design. Although patients with catheter-related bacteremia were similar in many respects, it is possible that the patients with bacteremia whose catheters were removed immediately were sicker than those in whom catheter salvage was attempted. This selection bias may have caused us to underestimate the likelihood of catheter salvage failure and may have obscured an increased risk for complications in patients whose catheters stayed in place for more than 3 days. In addition, we could not control for the type and duration of antimicrobial therapy in this type of observational study. Finally, although we determined the incidence of catheter-related infection, our study sample included patients whose catheters were already in place at the start of the study period as well as patients whose lines were placed during the study period. Thus, we could not control for the total length of time that the catheters were in place before the development of the first episode of catheter-related bacteremia. These design-related flaws could have been eliminated only by a randomized study; such a study is not practical, given the lack of alternatives for vascular access in this patient population.

We have shown that bacteremia is a frequent complication of dialysis that uses dual-lumen, tunneled, cuffed catheters. Although limited vascular access in many patients undergoing hemodialysis may lead to efforts to preserve existing vascular catheters even in patients with catheter-related bacteremia, the results of our study suggest that, in most instances, this strategy will not work. However, because attempted salvage does not seem to increase the incidence of complications, a trial of antibiotics alone may be warranted in a select group of patients in whom vascular access is particularly difficult, provided that these patients are hemodynamically stable and have no signs of tunnel infection. A thorough search for metastatic complications should be done in patients with S. aureus bacteremia who develop recurrent fever despite the long-term use of antibiotics. Future prospective studies are warranted to determine the utility of antibiotic- and silver-impregnated catheters designed to decrease associated infection as well as the optimal duration of antibiotic treatment for catheter-related bacteremia.

Drs. Schwab and Conlon: Duke University Medical Center, Division of Nephrology, Durham, NC 27705.