Catheter-Related Infections: It's All About Biofilm

Marcia A. Ryder, PhD, MS, RN

Disclosures

Topics in Advanced Practice Nursing eJournal. 2005;5(3) 

In This Article

Treatment of Catheter-Related Bloodstream Infections

Treatment should begin promptly following diagnosis, as the delay of appropriate antimicrobial therapy and/or catheter removal is associated with increased morbidity and mortality.[54,55,56] The treatment of CRBSI involves 2 strategies, the first consisting of antimicrobial therapy for systemic infection (bacteremia and accompanying metastatic disease, if present) and the second being the treatment of the catheter-associated biofilm as the source of infection.

Empiric broad-spectrum systemic antimicrobial therapy is initiated after the collection of appropriate samples, depending on the pathogen profile present in a given institution and the severity of the patient's illness. However, treatment should be de-escalated to narrow-spectrum antibiotics dependent on susceptibility testing of the isolated causative micro-organism(s) and the presence of associated complications. Therapeutic regimens for treatment of bacteremia and focal infection are well described in the evidence-based document, Guidelines for the Management of Intravascular Catheter-related Infections.[48]

Although antibiotic therapy and activated host defenses effectively kill planktonic organisms in the bloodstream, there is currently no form of treatment that will completely eradicate all biofilm cells associated with a catheter.[5] For this reason, removal of the device should be considered when an infection occurs. Prompt removal is strongly recommended in all cases complicated by metastatic infection or when the infection is caused by highly virulent or difficult to eradicate biofilm microorganisms such as S aureus, P aeruginosa, Corynebacterium spp., Bacillus spp., mycobacteria, and yeasts.[57] An overview of the recommended therapeutic approach to CRBSI is presented in Figure 4.

Treatment of catheter-related bloodstream infection. Adapted from Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis. 2001;32:1249-1272.

For uncomplicated cases of CRBSI with long-term catheters where removal is difficult or increases patient risk, or where venous access is limited, the antibiotic-lock salvage technique (ALT) might be attempted cautiously in conjunction with systemic therapy. The ALT consists of the instillation of an antibiotic sensitive to the causative organism with or without heparin at concentrations 100-1000 times higher than the target minimum inhibitory concentrations measured for systemic therapy.[48,58,59] The specified antibiotic in a concentration of 1-5 mg/mL mixed with 50-100 units of heparin (if compatible) or normal saline are "locked" in the catheter when the catheter is not in use (usually 12 hours over night).[48] The use of concentration-dependent-killing antibiotics such as the fluoroquinolones or aminoglycosides is optimal, rather than time-dependent-killing antibiotics such as beta-lactams or glycopeptides, so that minimum biofilm eradicating concentrations can be achieved without dependence on dwell time.[58] The recommended duration of therapy is 2 weeks.[48,57,58]

Two recent literature reviews evaluating the antibiotic lock technique provide an excellent overview of its use to date.[57,58] Most of the data in support of ALT relate to uncomplicated cases of coagulase-negative staphylococcal infections.[58] Due to the risk of infection recurrence or antimicrobial resistance with suboptimal dosing, and due to the difficulty of eradicating S aureus, Pseudomonas spp., or fungi, catheter removal is recommended in all but exceptional circumstances.

Antimicrobial agents other than antibiotics have been investigated for the treatment of intraluminal biofilm infection. The use of taurolidine,[60] ethanol,[61] hydrochloric acid,[62] and minocycline-EDTA[63] (M-EDTA) has produced limited and variable results. None of these agents are currently available commercially. Of the 4, M-EDTA appears to be the most effective, but minocycline is no longer being produced.

Another agent, tetrasodium EDTA, has been tested in vitro and ex vivo with explanted infected hemodialysis catheters.[64,65,66] Complete kill of biofilm bacteria and yeasts was observed within 24 hours of exposure. The ability to eradicate intraluminal biofilm within a few days would be quite advantageous over an extended and costly 2-week period. This agent is also a potent anticoagulant that could replace the use of heparin and eliminate the risk of heparin-induced thrombocytopenia. It appears to be a very promising agent for the prevention and treatment of CRBSI due to its capability to dissolve biofilm matrices, including those in conditioning films, and to eradicate all biofilm cells promptly. Further investigation is ongoing.

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