When and how to use antibiotic lock solutions

Antibiotic locks are instilled into the lumens of central venous catheters and allowed to "dwell" to kill microbial biofilms....
Abdelwahab Ward, BS Pharm, PharmD

QUESTIONS ARE COMING UP ABOUT ANTIBIOTIC LOCK THERAPY (ALT) OR WHEN AND HOW TO USE ANTIMICROBIAL LOCK SOLUTIONS. About one in 20 central venous catheters inserted will result in at least one systemic infection. These catheter-related bloodstream infections can increase hospital length of stay and hospital costs. The most common organisms are coagulase-negative staphylococci, S. aureus, enterococci, and Candida species.

Ideally, an infected catheter can be removed. However, in cases where a catheter can’t be removed, such as when a patient has limited vascular access or is unable to tolerate an interventional procedure, antimicrobial locks can be used in combination with systemic antibiotics to treat the infection. This therapy usually lasts for up to two weeks.

          When catheter cultures are positive and blood cultures are negative, antibiotic locks may be used alone for treatment to eradicate microbial biofilms within the catheter lumen. Antibiotic locks may also be useful to prevent recurrent catheter infections in patients with a history of multiple catheter infections. The concentration of the antibiotic should typically exceed 1000 times the MIC of the organism being treated. Volumes required to fill a catheter lumen are 2 to 5 mL. Antibiotic lock solutions should typically be allowed to dwell as long as the catheter is idle. It is recommended that dwell times do not exceed 48 hours. The following table (1) lists selected antimicrobial lock solutions along with dwell times and additional data on stability of combinations.

ANTIBIOTIC LOCK THERAPY

Table (1). Selected antibiotic lock therapy
Drug Concentration and Dwell Time Comments Additional Stability and Compatibility Information
Amikacin
 1 mg/mL
Dwell time up to 48 hours		 Stability data with heparin in lock solutions is limited to physical compatibility.

Amikacin 2 to 50 mg/mL with heparin 20 to 5000 units/mL has been given with no visual precipitation with dwell times of 3 to 16 days.
Cefazolin
 No efficacy data identified Cefazolin 10 mg/mL retains at least 90% potency at 37° C for 3 days.

Cefazolin 0.5 mg/mL with heparin 100 units/mL retains at least 95% potency of cefazolin at 37° C for 10 days.

Cefazolin 10 mg/mL with heparin 5000 units/mL retains almost 75% of cefazolin potency at 37° C for 3 days.
Ceftazidime
 5 mg/mL
Dwell time up to 48 hours
 With ceftazidime 2 mg/mL with heparin 100 units/mL, intraluminal concentrations of ceftazidime that exceed MICs of most isolates of susceptible organisms are maintained for 15 days.
Ciprofloxacin
 5 mg/mL
Dwell time up to 48 hours
 The compatibility of ciprofloxacin and heparin in lock solutions is unclear, and precipitation has been seen at most concentrations studied.
Daptomycin
 5 mg/mL
Dwell time up to 72 hours
 Mix in lactated Ringer’s solution to provide a calcium source, which is required for antibiotic effect.

Daptomycin 5 mg/mL in lactated Ringer’s solution with heparin 5000 units/mL retains 90% potency of daptomycin at 37° C for 24 hours.
Ethanol
 ≥ 40%
Dwell time of ≥ 30 minutes
(to eradicate Candida species in vitro)		 Ethanol 70% locks may be considered for the treatment of mixed gram-positive and gram-negative infections. Ethanol may also be useful for fungal infections.

Prophylaxis with an ethanol 70% lock solution significantly reduces the risk for catheter-related bloodstream infections compared with heparin locks in patients with cancer.

In general, ethanol may interact with components of catheters including silicone, polyurethane, or polycarbonate. However, ethanol 70% appears to be compatible with silicone or polyurethane catheters.

Ethanol 70% with heparin 10 units/mL appears to be compatible for up to 72 hours.

Ethanol must be aspirated rather than pushed through into the IV line in order to avoid side effects such as dizziness.
Gentamicin
 13.3 mg/mL
Dwell time up to 12 hours		 Gentamicin 5 mg/mL with heparin 5000 units/mL retains > 90% potency of gentamicin inside a central venous catheter for 3 days.
Telavancin
 No efficacy data identified
 Telavancin 2 mg/mL or 5 mg/mL with heparin 2500 units/mL retains at least 90% potency of telavancin at 37° C for 3 days.
Vancomycin
 5 mg/mL
Dwell time up to 72 hours
 Vancomycin 2 mg/mL or 5 mg/mL with heparin 2500 units/mL retains at least 90% potency of vancomycin at 37° C for at least 3 days.

Lower concentrations of vancomycin, such as 25 mcg/mL, with shorter dwell times, such as 60 minutes, are typically used for prophylaxis, in comparison with the higher concentrations (1000 times the organism’s MIC) for treatment of catheter infections.

BACKGROUND
Antibiotic locks are instilled into the lumens of central venous catheters and allowed to "dwell" to kill microbial biofilms. They can be added to systemic treatment for infections of long-term catheters when the catheter can't be removed. Or they can be used alone for prophylaxis in patients with a history of catheter infections. Use these tips when considering antimicrobial lock therapy... 
  • CHOOSING AN AGENT. For treatment, use the same antimicrobial that's being given systemically if possible. For prophylaxis, consider vancomycin. Add an anticoagulant (usually heparin) if needed to prevent clotting of the catheter. Ethanol might be useful for bacterial or fungal catheter infections. But it can cause side effects such as dizziness if accidentally pushed through into the IV line. 
  • DETERMINING A FORMULATION. For treatment, choose an antimicrobial concentration of at least 1000 times the MIC (often 1 to 5 mg/mL). Order enough volume to cover the inside surface of the catheter lumen (usually 2 to 5 mL depending on the type of catheter). If a lock contains multiple drugs (such as gentamicin plus heparin), make sure they're compatible. 
  • ENSURING STABILITY. Make sure the antimicrobial will be stable throughout the dwell time from just a few hours up to 48 hours or more. 

REFERENCES

Abdelwahab Ward, BS Pharm, PharmD