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Antibiotic lock solution concentrations for adjunctive treatment of non-hemodialysis catheter-related bloodstream infection (CRBSI)

Antibiotic lock solution concentrations for adjunctive treatment of non-hemodialysis catheter-related bloodstream infection (CRBSI)
  Antibiotic agent Antibiotic concentration Heparin concentration Maximum dwell time (duration of stability)* References
Antibiotic agents with activity against gram-positive organisms Vancomycin 2.5 mg/mL 2500 units/mL 72 hours Krishnasami[1]
5 mg/mLΔ 5000 units/mL 72 hours Luther[2]
5 mg/mL none 72 hours Luther[2]
Cefazolin 5 mg/mL◊ 2500 units/mL 72 hours Krishnasami[1]
5 mg/mL§ none 48 hours Vercaigne[3]
10 mg/mL 5000 units/mL 72 hours Vercaigne[3]
Daptomycin 5 mg/mL¥ 5000 units/mL 72 hours LaPlante[4]
5 mg/mL none 72 hours LaPlante[4]
Nafcillin 100 mg/mL none 12 hours Nafcillin[5]
Ampicillin 10 mg/mL‡ none 8 hours Ampicillin[6]
Antibiotic agents with activity against gram-negative organisms Gentamicin 1 mg/mL† 2500 units/mL 72 hours Krishnasami[1]
5 mg/mL** 5000 units/mL 72 hours Vercaigne[3]
5 mg/mL none 72 hours Vercaigne[3]
Ceftazidime 10 mg/mL¶¶ 5000 units/mL 48 hours Vercaigne[3]
1 to 10 mg/mL none 48 hours Lee[7]
Cefepime 1 to 10 mg/mL none 48 hours Lee[7]
Ciprofloxacin 1 to 5 mg/mL none 48 hours Lee[7], Lee[8]
Ceftriaxone 100 mg/mL none 48 hours Ceftriaxone[9]
  • Antibiotic lock solutions for the treatment of CRBSIs in the setting of catheter salvage should be used in conjunction with systemic antibiotic therapy. Refer to the UpToDate topics on treatment of CRBSI for further discussion. Refer to the UpToDate topic on hemodialysis catheter infections for discussion of approach to ALT in this setting.
  • The choice of antibiotic for ALT should be guided by the antimicrobial susceptibility of the infecting organism. There is no standard antibiotic or dosing regimen for use in ALT; thus far, there have been no rigorous studies comparing antibiotic lock solutions.
  • The solutions in the table are standardized to a 2 mL volume. If larger volumes are needed to fill the catheter lumen, the quantities should be adjusted accordingly.
  • Heparin is commonly used in ALT solutions to help maintain catheter patency; however, there are no comparative clinical studies demonstrating that ALT solutions containing heparin are more effective than solutions without heparin. Lock solutions with chemical compatibility between heparin and antimicrobial agents are summarized above; use of antibiotic lock solutions without heparin is also acceptable.
  • Ideally, ALT should be instilled at least once daily. The optimal dwell time is uncertain; dwell times may range from hours to days, depending on stability of the lock solution and the amount of time available when the catheter is not in use. Some studies support a minimum dwell time of 8 to 12 hours. Antibiotic concentrations may fall to subtherapeutic levels in the distal lumen of the catheter when dwell times exceed 48 to 72 hours.
  • If the line must be accessed for alternate use during the dwell time, the lock solution should be removed and later replaced with fresh solution.
ALT: antibiotic lock therapy.
* While antibiotics may remain stable in lock solutions based on their physical and chemical stability, in general, we favor limiting the dwell time to 24 to 48 hours, since antibiotic concentrations in the catheter can fall to subtherapeutic levels over time.
¶ Vancomycin-heparin solution prepared by mixing vancomycin (0.5 mL of 10 mg/mL solution diluted in normal saline) plus heparin (0.5 mL of 10,000 units per mL solution) with 1 mL of normal saline for a final concentration of vancomycin 2.5 mg/mL and heparin 2500 units/mL in a 2 mL solution.
Δ Vancomycin-heparin solution prepared by mixing vancomycin (1 mL of 10 mg/mL solution diluted in normal saline) plus heparin (1 mL of 10,000 units per mL solution) for a final concentration of vancomycin 5 mg/mL and heparin 5000 units/mL in a 2 mL solution.
◊ Cefazolin-heparin solution prepared by mixing cefazolin (1 mL of 10 mg/mL solution diluted in normal saline) plus heparin (0.5 mL of 10,000 units per mL solution) with 0.5 mL of normal saline for a final concentration of cefazolin 5 mg/mL and heparin 2500 units/mL in a 2 mL solution.
§ Cefazolin-heparin solution prepared by mixing cefazolin (1 mL of 20 mg/mL solution diluted in normal saline) plus heparin (1 mL of 10,000 units per mL solution) for a final concentration of cefazolin 10 mg/mL and heparin 5000 units/mL in a 2 mL solution.
¥ Daptomycin-heparin solution prepared by mixing daptomycin (1 mL of 10 mg/mL solution diluted in lactated Ringer's) plus heparin (1 mL of 10,000 units per mL solution) for a final concentration of daptomycin 5 mg/mL and heparin 5000 units/mL in a 2 mL solution.
‡ Ampicillin should be diluted with normal saline, lactated ringers, or sterile water for injection to achieve 8-hour stability; the stability of ampicillin is limited if diluted with 5% dextrose in water.
† Gentamicin-heparin solution prepared by mixing gentamicin (0.5 mL of 4 mg/mL solution diluted in normal saline) plus heparin (0.5 mL of 10,000 units per mL solution) plus 1 mL of normal saline solution for a final concentration of gentamicin 1 mg/mL and heparin 2500 units/mL in a 2 mL solution.
** Gentamicin-heparin solution prepared by mixing gentamicin (1 mL of 10 mg/mL solution diluted in normal saline) plus heparin (1 mL of 10,000 units per mL solution) for a final concentration of gentamicin 5 mg/mL and heparin 5000 units/mL in a 2 mL solution.
¶¶ Ceftazidime-heparin solution prepared by mixing ceftazidime (1 mL of 20 mg/mL solution diluted in normal saline) plus heparin (1 mL of 10,000 units per mL solution) for a final concentration of ceftazidime 10 mg/mL and heparin 5000 units/mL in a 2 mL solution.
References:
  1. Krishnasami Z, Carlton D, Bimbo L, et al. Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution. Kidney International 2002; 61:1136.
  2. Luther MK, Mermel LA, LaPlante KL. Comparison of linezolid and vancomycin lock solutions with and without heparin against biofilm-producing bacteria. Am J Health-Syst Pharm 2017; 74;e193.
  3. Vercaigne LM, Sitar DS, Penner SB, et al. Antibiotic-heparin lock: in vitro antibiotic stability combined with heparin in a central venous catheter. Pharmacotherapy 2000; 20:394.
  4. LaPlante KL, Mermel LA. In vitro activity of daptomycin and vancomycin lock solutions on staphylococcal biofilms in a central venous catheter model. Nephrol Dial Transplant 2007; 22:2239.
  5. Nafcillin [package insert]. Dayton, NJ: AuroMedics Pharma LLC; 2013.
  6. Ampicillin [package insert]. New York, NY: Pfizer Inc; 2010.
  7. Lee MY, Ko KS, Song JH, Peck KR. In vitro effectiveness of the antibiotic lock technique (ALT) for the treatment of catheter-related infections by Pseudomonas aeruginosa and Klebsiella pneumoniae. J Antimicrob Chemother 2007; 60:782.
  8. Lee JY, Ko KS, Peck KR, et al. In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci. J Antimicrob Chemother 2006; 57:1110.
  9. Ceftriaxone [package insert]. Lake Forest, IL: Hospira Worldwide Inc; 2015.
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