Consider antibiotic line lock therapy for treatment of catheter-related infections

May 2005

According to the Infectious Diseases Society of America (IDSA), more than 5 million central venous catheters (CVCs) are placed in patients every year. These catheters can be described as nontunneled catheters, tunneled catheters or totally implantable devices.

Tunneled catheters include Hickman, Broviac, Groshong and Quinton catheters. Tunneled catheters and totally implantable devices like ports are frequently used when long-term intravenous access is required, such as in patients receiving long-term total parenteral nutrition (TPN), dialysis, chemotherapy, cystic fibrosis patients and HIV patients.

In the United States, more than 200,000 nosocomial bloodstream infections occur yearly. Approximately 11% to 37% of these infections have been shown in studies to be related to CVCs. Most catheter-related infections are seen with nontunneled CVCs; however, these infections can also occur with tunneled CVCs or ports.

Risk factors for the development of a catheter-related infection include the type of catheter, insertion site, how long the catheter is in place, neutropenia, AIDS and presence of malignancy.

Pathogenesis

Catheter-related infections may occur with nontunneled catheters by three mechanisms. First, the catheter can become colonized on the outside of the lumen with organisms present on the skin. Another mode of infection is seeding the catheter tip from infections present in the blood. Finally, the lumen of the catheter can become colonized with bacteria. Tunneled catheters or implantable devices can become a source of infection most commonly by colonization of the catheter hub and inside the lumen.

The most common organisms responsible for causing catheter-related infections are gram-positive bacteria, such as coagulase-negative staphylococci and Staphylococcus aureus. Other organisms that can cause catheter-related infections include aerobic gram-negative bacilli and Candida albicans.

The IDSA has published clinical guidelines on the treatment of catheter-related infections. For the treatment of nontunneled CVC-related bacteremia, removal of the catheter and treatment with systemic antibiotics or antifungal agents, depending on the organism, is recommended. Treatment with antibiotics or antifungal agents should last 14 days unless the infection is complicated, such as in patients with endocarditis or osteomyelitis. Salvage therapy for the catheter, ie, antibiotic line lock therapy, should only be considered in patients with uncomplicated bacteremia caused by coagulase-negative staphylococci in conjunction with systemic antibiotics for 10 to 14 days.

Treatment recommendations for catheter-related bacteremia in patients with tunneled CVCs or implantable devices differ somewhat.

Catheter-related infections caused by Candida spp. require removal of the line as well as systemic antifungal therapy. Complicated infections such as endocarditis, osteomyelitis, septic thrombosis, tunnel infection or port abscess also require removal of the catheter or implantable device and systemic antibiotic treatment. Uncomplicated infections caused by coagulase-negative staphylococci, S. aureus or gram-negative bacilli should be treated by removing the catheter or implantable device and initiating systemic antibiotic therapy. However, for infections caused by coagulase-negative staphylococcus, S. aureus or gram-negative bacilli, if removing the catheter is not desired, salvage therapy for the catheter may be attempted using the antibiotic line lock therapy along with systemic antibiotic therapy for 14 days. If the bacteremia does not clear, the infection relapses, or clinical deterioration occurs, salvage therapy must be abandoned and the catheter should be removed.

Because of the expense, time and difficulty of finding new access sites, insertion of a new CVC is not always desirable. One technique for salvaging catheters is antibiotic line lock therapy. This consists of inserting antibiotics into the lumen of the catheter with doses approximately 100 to 1,000 times higher than what is given systemically and allowing the antibiotics to dwell in the catheter for a prolonged period.

Only certain patient populations may potentially receive antibiotic line lock therapy along with systemic antibiotics. The following patient populations may be considered for antibiotic line lock therapy:

• Uncomplicated infections in patients with nontunneled CVCs caused by coagulase-negative staphylococci
• Uncomplicated infections in patients with tunneled CVCs or ports caused by coagulase-negative staphylococci, Staphylococcus aureus or gram-negative bacilli

The following patient populations should not be considered at any time for the antibiotic line lock therapy:

• Complicated infections including endocarditis, osteomyelitis, tunnel infection, port abscess or septic thrombosis
• Uncomplicated infections caused by Candida spp.
• Uncomplicated infections caused by S. aureus or gram-negative bacilli in patients with nontunneled catheters

Preparation/technique

Solutions of the desired antibiotic should be mixed with heparin or normal saline in an appropriate volume to fill the lumen of the catheter, usually 5 mls. The IDSA guidelines recommend using 50 to 100 units of heparin in this solution. The solution is then “locked” in the catheter lumen for a time, usually 12 hours. The catheter should not be used while the antibiotic lock solution is in place and the solution should be removed before use of the catheter resumes.

A variety of antibiotics have been reported to be used in antibiotic line lock therapy. Vancomycin, gentamicin, amikacin and ciprofloxacin are the antibiotics most frequently reported in the medical literature, although ceftazidime and cefazolin have also been used. The stability of these antibiotics with heparin differs among agents and specific dosing and stability information will be discussed for each agent below.

Vancomycin has been used clinically in antibiotic line locks at concentrations ranging from 1 to 5 mg/ml. It has been shown to be chemically stable with heparin in concentrations of up to 10 mg/mL. The vancomycin/heparin solution is stable at 37°C for up to 72 hours.

Gentamicin has been used clinically in concentrations of 1 mg/mL to 2 mg/mL. It has been shown to be chemically stable with heparin at concentrations of up to 4 mg/mL. This solution is also stable at 37°C for up to 72 hours.

Amikacin has been clinically used in concentrations of 1 mg/mL to 2 mg/mL. Information on its stability with heparin is not available. Amikacin solutions are stable at 4°C for 14 to 17 days.

Cefazolin has been clinically used at a concentration of 5 mg/mL. Cefazolin has shown a possible interaction with heparin when concentrations of 10 mg/mL were used, however, this interaction was not visually present at 5 mg/mL or chemically present at 500 µg/mL. The cefazolin/heparin solution is stable at 37°C for 72 hours.

Ceftazidime has been clinically used at a concentration of 0.5 mg/mL. It is chemically stable in solution with heparin at concentrations of up to 10 mg/mL at 37°C for 72 hours.

Ciprofloxacin has been clinically used at concentrations of 1 mg/mL to 2 mg/mL. It has poor stability with heparin, however, and is only chemically stable at doses up to 125 µg/ml. This ciprofloxacin/heparin solution is stable for 10 days at 37°C.

Antibiotic line locks are an option for certain patients with catheter-related bacteremia when removal of the CVC is not desired. This option should only be used in select patient populations and should always be used with systemic antibiotics, never alone. Information on the success of antibiotic line locks is still limited, and their use in clinical practice should be carefully evaluated.

For more information:

• O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2002;35:1281-1307.

• Rebekah R. Arthur, PharmD, is an assistant professor of pharmacy practice, Campbell University School of Pharmacy, Duke University Medical Center.