Treatment and prevention of catheter-related infections in haemodialysis patients

Peter J. Blankestijn

Department of Nephrology, University Medical Center, Utrecht, The Netherlands

Keywords: catheter-related infection; haemodialysis

Introduction

The most important catheter-related complications, which determine method survival, are infection and dysfunction. In particular, infectious episodes are in some studies the leading cause for untimely catheter removal and for catheter-related morbidity but also for morbidity in dialysis patients. For instance, in one study involving 988 dialysis patients it was estimated that the relative risk for bacteraemia was increased more than 7-fold in patients with catheters than in those with AV fistulas [1]. Therefore, identifying appropriate treatment regimens of documented infections, and of measures aimed to prevent infections, is of major clinical relevance.

We have to distinguish between catheters meant for temporary use (i.e. not more than a few weeks) and catheters meant to be in place for months, maybe years.

We will briefly touch first upon temporary catheters and review the updated KDOQI guidelines, which were released in early 2001. Subsequently we will address the issue of treatment and prevention of infections in permanent catheters [2].

Although the so-called permanent catheters were introduced more than a decade ago, their popularity has been mainly increasing in the last few years. In the US, approximately 20% of patients are dialysed using permanent catheters at day 60 after initiation of dialysis therapy. To our knowledge the ERA-EDTA does not present data on this issue.

Pathogenesis

Understanding the pathogenesis of catheter-related infection will help to define strategies for treatment and especially for prevention. This subject was comprehensively reviewed recently [3,4].

It has been shown that almost all in-dwelling vascular catheters are colonized by micro-organisms. These micro-organisms are usually imbedded in a biofilm layer, are metabolically active and viable, and can already be present 24 h after insertion. There is a link between the number of organisms retrieved by culture from the catheter surface and the risk of infection associated with these catheters. Only a few of the micro-organisms embedded in biofilm cause bloodstream infection. Infection depends on whether the organisms on the catheter surface exceed a certain quantitative threshold.

Organisms causing bloodstream infections generally enter the bloodstream from the skin insertion site or through the hub of the catheter. Haematogenous seeding and contamination of infused fluids are possible causes as well. Skin organisms migrate from the skin insertion site along the external surface of the catheter, colonizing the distal intravascular tip of the catheter and ultimately causing bloodstream infection. Organisms may be introduced into the hub by the hands of medical personnel. The subsequent colonization of the internal surface of the catheter may also cause bloodstream infection.

Microbiological analysis of catheter-related bloodstream infections shows a clear predominance of skin derived micro-organisms, especially Staphylococcus epidermidis and Staphylococcus aureus, but Streptococcus, Bacillus and Corynebacterium species can be found as well.

In a recent study, weekly blood cultures were taken from temporary jugular and subclavian vein catheters. Positive cultures were found after 5–126 days after insertion indicating colonization. In most colonized catheters, bacteraemia (i.e. positive blood cultures from a peripheral vein) followed within 4–6 weeks [5].

Exit site infection is defined as redness, crusting and exudate at the exit site in the absence of systemic symptoms and with negative blood cultures. Culture of drainage material will confirm the diagnosis.

Catheter-related bacteraemia may occur with and without symptoms of systemic illness. A single positive culture of blood drawn from the catheter can indicate either intraluminal catheter colonization or hub contamination, rather than bloodstream infection. Quantitative culture methods may be particularly helpful but are not universally available. Paired quantitative blood cultures should be used to diagnose catheter-related bloodstream infection. The diagnosis is suggested when the number of colonies isolated from the blood culture sampled through the catheter is at least five times greater than that seen in the blood culture derived from peripheral sampling.

Temporary catheters
In a recent study on 318 temporary catheters, it was reported that the incidence of bacteraemia due to jugular vein catheters was 5.4% after 3 weeks and that it was 10.7% with femoral vein catheters after 1 week [6]. The presence of an exit site infection increases that risk substantially, with an 11% incidence 2 days after and a 19% incidence 5 days after onset of the exit site infection. Interestingly, guidewire exchange for malfunction did not increase the risk of bacteraemia.

The recommendations by the KDOQI Work Group are quite clear: exit site, tunnel tract or systemic infections require removal of temporary catheters. Obviously, not every patient with a catheter and fever has a catheter-related bacteraemia. So, if the patient is not clinically unstable, an appropriate approach may be to draw a blood culture from a peripheral vein, start antibiotics, and remove the catheter if the blood culture turns out to be positive.

Permanent catheters
Many clinicians feel reluctant to remove the catheter, because most patients with cuffed tunnelled catheters have exhausted all other options for vascular access. On the other hand, tunnel infections and catheter-related bacteraemias with or without clinical symptoms are serious complications and should be addressed adequately. The incidence of catheter-related bloodstream infection ranges from 0.016 to 0.39 events per 100 catheter days (summarized in [7]). They are associated with substantial morbidity, including metastatic infections, and even mortality. Parenteral antibiotics should be given in all cases.

Some older, uncontrolled studies have indicated that salvage of the catheter is possible with antibiotics alone. Several recent studies related to this subject need to be discussed in some detail.

One study systematically investigated the outcome of catheter-related bacteraemia and of the attempted salvage of the catheter [8]. The authors reported that in only 12 out of 38 cases of catheter-related bacteraemia and of attempted catheter salvage, was this approach actually successful. Catheter salvage was considered successful if the catheter was still in place 3 months after the episode of bacteraemia or if the catheter was removed for reasons other than persistent or recurrent infection. In the remaining two thirds of patients, antibiotic treatment was considered to be a failure because blood cultures continued to show the initial micro-organism or the patients continued to have fever. In 22% of the patients with bacteraemia serious complications occurred, including osteomyelitis, arthritis, endocarditis or death. However, this outcome was no more likely to occur in patients in whom the catheter was attempted to be salvaged.

In another study, a different approach was chosen and the outcome of 123 episodes of catheter-related infections reported [9]. The treatment modality was based on the clinical symptoms: minimal symptoms with clean exit site, exchange over guidewire within 48 h; minimal symptoms with exit site or tunnel infection, exchange over guidewire within 48 h plus new tunnel; severe symptoms, catheter removal and delayed replacement. In all cases, a course of 3 weeks antibiotic administration was applied. In all three groups cure rate was approximately 80%. This study indicates that, in selected patients, the option of replacement over guidewire may be appropriate. It also indicates that decision-making led by the clinical presentation is a reasonable approach.

In a recent report, yet another treatment regimen was presented [10]. It included catheter removal when there was severe sepsis, fever persisting for more than 48 h of antibiotic treatment and/or clear-cut exit site infection. In the remaining cases, two strategies were compared: replacing the catheter over guidewire or removal of the catheter and re-introduction 3–10 days later. In all cases antibiotics were given for approximately 3 weeks. The main finding of this study was that a positive outcome, that is an infection-free interval after appropriate antibiotic treatment, did not differ in the two groups, indicating that the guidewire exchange approach is appropriate in a selected set of patients with clinically mild infections.

The KDOQI Work Group summarizes the available data as follows (Guideline 26). The exit site infection should be treated with topical antibiotics (this is an opinion statement). In case of tunnel infection, parenteral antibiotics should be given and the catheter not to be removed unless infection fails to respond to therapy (opinion and evidence). Catheter-related bacteraemia with or without severe clinical symptoms requires parenteral antibiotics appropriate for the organism suspected, usually Staphylococcus or Streptococcus (evidence); definitive therapy should be based on the organism(s) isolated. The catheter should be removed when a patient remains symptomatic for more than 36 h, and in any clinically unstable patient. In stable patients, an exchange over guidewire may be appropriate. A minimum of 3 weeks of antibiotics is needed.

Prevention

Strategies should be aimed to prevent colonization of the external surface of the catheter and of the catheter lumen.

Insertion of the catheter should be done as a sterile procedure. Reported differences in infection rates must at least in part be attributed to the skills and the degree of alertness of the dialysis staff. The latter should be specifically trained how to manipulate the catheter properly. All catheter manipulations should be done exclusively by such trained personnel. The recommendations formulated by the KDOQI Work Group are summarized in Table 1Go. The use of dry gauze dressings with povidone iodine ointment at the catheter exit site can reduce exit site infections. Dry gauze is recommended rather than transparant film dressings because transparent film dressings pose a greater risk for exit site colonization.


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Table 1. Measures during catheter manipulations aimed at reducing catheter-related bloodstream infections (adapted from [2])

 
In a recent study, temporary catheters were prospectively randomized to either mupirocin application around the catheter insertion site or no such application [11]. An equal number of catheters were randomized but the total number of days in place in the treated group was much longer, mainly because of less need for untimely removal. There was a dramatic reduction in the incidence rates per 1000 patient days of S. aureus-related infectious complications. Although not formally investigated, it is likely that this approach is also useful for permanent catheters.

Some data are available on the option of an antibiotic-containing lock in permanent catheters. Sodeman and colleagues reported at the 1997 ASN meeting that, by applying a gentamicin/citrate mixture into the catheter once weekly, the incidence of catheter-related bacteraemias could be reduced to virtually zero [12]. These results look extremely promising; however, they have not yet been published as a full article.

Available data in the literature do not support the idea that the administration of antibiotics during the introduction procedure reduces infections, although this has not been formally tested in haemodialysis patients.

Given the importance of microbial adherence to the catheter surface in the pathogenesis of infection, a strategy to render the outer surface of the catheter more resistant to colonization, would be worth testing. Bonding of an antibiotic to the catheter before insertion reduced catheter-related infection in intensive care patients. This approach has not been tested in haemodialysis patients. An important issue in these patients is that antimicrobial activity needs to be exerted for much longer than up to 2–3 weeks as presently reported.

There is one study evaluating silver coated, tunnelled catheters in a prospective randomized fashion. However, the incidence of infection was not reduced [13]. There are no data indicating that any catheter material is more or less associated with catheter-related infections than other materials.

Because the presence of the transcutaneous tunnel is a risk factor for bacteria entering the bloodstream, a subcutaneous device may reduce this risk. The Dialock is such a device [14]. Like in haemodialysis grafts, this foreign body can also get infected. If the device is not removed, prolonged treatment with antibiotics is necessary. There is some anecdotal evidence that this may be successful. Whether application of an antibiotic-containing mixture reduces this risk is worth investigating.

Conclusion

It is important to realize that relatively simple measures can markedly reduce the incidence of catheter-related infections. These measures include a strict catheter handling protocol and the application of povidone or muporicin around the insertion site. With respect to treatment of infectious periods, it is clear that this remains a serious clinical condition because it is associated with substantial morbidity and even death. There is now evidence that the catheter does not need to be removed in all patients with documented infections. Close surveillance of the clinical condition, often combined with exchange over guidewire, may salvage the catheter site in carefully selected dialysis patients.

Notes

Correspondence and offprint requests to: Peter J. Blankestijn, Department of Nephrology, Room F03.226, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. Email: p.j.blankestijn{at}digd.azu.nl Back

References

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