Antibiotic Lock Solutions in the Prevention of Catheter Related Bacteremia
Condition: ESRD
Study type: Interventional
Phase: Phase 4

Summary: 
      To study the efficacy of an antibacterial/anticoagulant solution instilled into the
      hemodialysis (HD) catheters after each treatment ("antibiotic lock solution - ALS") to
      prevent catheter related bacteremia (CRB) and to salvage catheters with established CRB.
    

Detailed description: 
      Scope of the problem. A large number of hemodialysis patients in this country rely on
      indwelling tunneled and non-tunneled catheters as vascular access for hemodialysis even
      though the K/DOQI guidelines discourage their use. In a study performed by ESRD network 11,
      [to which all Michigan dialysis centers submit data] 63% of patients initiated HD with a
      catheter as their sole form of vascular access. At 6 months after initiation of HD, 40% of
      these patients were still using a catheter. Other studies had shown that the prevalence of
      overall catheter use to be around 20% of all accesses.

      Catheter associated infection. Current literature indicates that these catheters are
      associated with a disproportionate risk for infection, particularly CRB, resulting in high
      morbidity, mortality and healthcare expenditure. The 'epidemic' of ESRD in this country has
      seen an ever increasing reliance on these catheters not only to initiate the HD but also for
      long term treatment in those patients who have no other access options. It has been estimated
      that intravascular catheters are associated with more than 60,000 cases of nosocomial
      bacteremia each year. HD catheters pose a particularly high risk for developing infections
      because of their frequent use as well as their long-term use. All indwelling vascular
      catheters are colonized by micro-organisms within 24 hours after insertion. The deposition of
      biofilm on the external and internal surface of vascular catheters is thought to play an
      important role in the colonization process. The biofilm is produced by a combination of host
      factors (e.g., fibrinogen, fibrin, fibronectin and extracellular polysaccharides) and
      microbial products (e.g., glycocalyx or "slime").

      Failure of antibiotics. Systemic antibiotics used to treat bacteremia do not penetrate
      catheter lumen and therefore do not eradicate the biofilm, leading to potential treatment
      failures and eventual sacrifice of the catheter. Recently published data suggests that using
      a combination solution with antibacterial/anticoagulant agents prevents the formation of the
      'biofilm' in the catheter lumen thereby preventing CRB, as well as salvage the catheters in
      cases of established CRB. However, there continues to be a debate on the appropriate
      antibacterial agent as well as its optimal concentration, in order to eradicate a wide
      variety of organisms. Several other strategies were studied in the past 10 years to prevent
      CRB and CRI. These include eradication of nasal Staphylococcal carriage with mupirocin, using
      chlorhexidine for catheter hub cleaning and exit site disinfection and using mupirocin or
      Polysporin ointments to the exit site along with standard dressing. But emergence of
      antibiotic resistance as well as the high costs of administrating these methods continue to
      be barriers to their widespread use and cannot be relied upon to manage the high rate of
      infection by themselves.

      Salvaging catheters. In the past, infected catheters were routinely removed, especially for
      Staphylococcus aureus infections, per the CDC guidelines. However, recent small studies
      indicate that strategies such as ALS packing or changing catheter over a guide wire can
      salvage a significant fraction of these catheters, thereby saving expense and morbidity, and
      preserving the site. Thrombotic occlusions and infection are the two most common
      complications of the HD catheters, each predisposing to the other. Some studies have shown
      that ALS packing has also improved the long-term catheter function by preventing the
      formation and propagation of the biofilm. Studying this aspect of catheter maintenance is
      also an important outcome for our proposed study.

      Antibiotic Lock Solutions. We have identified 10 clinical trials (attached as appendix) in
      the published literature describing the results of antibiotic lock therapy for preventing
      infections in indwelling vascular catheters. All but one have demonstrated efficacy of ALS
      packing. Of the 9 successful trials, only 6 were randomized controlled trials and only 3 of
      these were done on HD catheters, as described below.

      Need for a prospective study. If we can achieve the same superior results from our study
      incorporating the ALS packing strategy, we should be able to assess cost- effectiveness of
      using the ALS packing vs. standard approach as has been discussed in previous trials, but has
      not been systematically studied. In fact there are insufficient numbers of patients studies
      to even perform a meta-analysis. We feel that it is critical to prove the cost-effectiveness
      of the new strategy in order for it to be used in a widespread fashion.

      The applicant, Anatole Besarab MD, has extensive experience in Nephrology and specifically in
      vascular access management. He has published, lectured, and coordinated symposia on vascular
      access care and is the current chair of the K/DOQI vascular access workgroup of the NKF.

      This project is conceived for the following reasons.

        -  The CRB burden in the hemodialysis patients at this institution has reached overwhelming
           proportions and needs urgent strategies to counter this 'epidemic'. Current management
           guidelines rely mostly on treatment of established infections but do not aim at
           preventing these infections. This kind of economic burden and increased
           morbidity/mortality in patients are unacceptable in the current health care environment.
           Our study will add to the existing literature in defining the management guidelines for
           CRB.

        -  The Greenfield Health System (GHS) that provides dialysis care to the patients of the
           Henry Ford Health System includes several hundreds of patients and would be the ideal
           setting to study the proposed intervention. This population also represents a
           cross-section of many types of disease severity and number of co-morbid conditions.
           Therefore they provide an opportunity to observe the effects on the proposed
           intervention in different demographic settings.

        -  Henry Ford Hospital represents a completely new demography to study the effects of the
           proposed intervention. The disease burden with CRB in the population served by this area
           is higher than the national average and would be ideal to study the proposed
           intervention in more detail.

        -  The cost effectiveness of using the antibiotic lock therapy has not been well studied to
           date and will have a significant impact on the eventual formulation of treatment
           guidelines. In the setting of current economic burden in the health care industry, study
           of this issue is vital and timely. The vision of a simple, cheap intervention that can
           result in savings of millions of dollars is central to this study.
    

Intervention name(s): Gentamycin/citrate, Minocycline/EDTA
Intervention type(s): Drug
Intervention MeSH terms: Minocycline; Gentamicins
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention