Antibiotic Lock Therapy in Adults

Modified Date: 
December 15, 2020

 

SECTION A: EXECUTIVE SUMMARY

  • Antibiotic lock therapy (ALT) is most commonly considered for adjunctive treatment of bacteremia associated with central venous catheters (CVC).
  • ALT can also be considered for prophylaxis of bacteremia for certain populations.

 

SECTION B: ANTIBIOTIC LOCK THERAPY (ALT)

  • KEY CONCEPTS
    • ALT is most commonly used for adjunctive treatment of bacteremia associated with CVC when the CVC is not removed.
    • Prophylactic use of ALT may be considered for select patients, e.g. patients deemed at high risk for recurrent bloodstream infection.
    • is not intended to be administered via the routes of IV infusion or IV push.
    • dwell time is 4-24 hours. Duration of dwell time should not exceed 24 hours (see IV: Dwell Time and Exchange Frequency).
  • PATIENT ELIGIBILITY
  • associated with central venous catheter (CVC)
  • Prophylaxis for recurrent blood stream infections (BSIs) in high-risk patients
  • Prior to intiatiating ALT, all ALT candidates require consultation and approval by Infectious Diseases Consult Service
  • CONTRAINDICATIONS
    • History of heparin-induced thrombocytopenia (HIT) for ALT-containing heparin. Gentamicin lock is an exception as it does not contain heparin.
    • Allergy to any component in the lock.
    • or religious exclusion to ingestion of pork components if lock contains heparin.  Gentamicin lock is an exception as it does not contain heparin.
    • Catheter tunnel or exit site infect.
  • ALT Doses
    • ALT recipes listed in Appendix C
    • Other antibiotic locks may be considered per Infectious Diseases as needed

 

Antibiotic

Antibiotic Concentration

Additive Concentration

Stability

Cefazolin

10 mg/mL

Heparin 10 units/mL

30 hours

Ceftazidime

10 mg/mL

Heparin 10 units/mL

30 hours

Gentamicin

2.5 mg/mL

Sodium Citrate 40 mg/mL (4%)

30 hours

Linezolid

1 ml/mL

Heparin 10 units/mL

30 hours

Vancomycin

2 mg/mL

Heparin 10 units/mL

30 hours

  • Catheter and Volume Selection

Catheter Type

Volume per lumen

PICC, Tunneled or Non-Tunneled Central catheter (e.g. Broviac)

2 mL

Implanted Vascular Access Port (e.g. Port-A-Cath)

5 mL

  • Dwell Time and Exchange Frequency
    1. Range of dwell time is 4-24 hours.  Duration of dwell time should not exceed 24 hours.  Lock solution should generally remain in place (dwelling) whenever the affected line/lumen is not in use.  The number of ALT exchanges per day should be coordinated between pharmacy and the RN.
    2. Pharmacy and nursing should work to cluster required medications and/or lab draw times to minimize catheter use and maximize ALT dwell times.

 

  • PHARMACY OPERATIONS
    • to send 2 mL of antibiotic lock solution in a 10 mL syringe for each lumen of a PICC, Tunneled or Non-Tunneled Central catheter (e.g. Broviac)
    • to send 5 mL of antibiotic lock solution in a 10 mL syringe for each lumen of an implanted Vascular Access Ports (e.g. Port-A-Cath)
    • Heparinized antibiotic locks to be formulated with normal saline only.
    • Room temperature (23-25˚C).
    • Label warnings: For antibiotic lock therapy into CVC lumen only

 

  • NURSING ADMINISTRATION
    • To place antibiotic lock therapy:
      1. patient and procedure using 2 patient identifiers.
      2. hand hygiene. Don clean gloves.
      3. Vigorously scrub the needleless connector for 10 seconds with alcohol pad and allow to dry for 10 seconds.
      4. If ALT in place, attach a 10 mL syringe and aspirate volume of lock plus 1-2 mLs to remove any clots at the tip. Remove syringe and discard. Repeat step 3. If no ALT in place, proceed to step 5.
      5. a pre-filled normal saline syringe and flush CVC with 10mL of normal saline; remove and discard syringe.
      6. Vigorously scrub the needleless connector for 10 seconds with alcohol pad and allow to dry for 10 seconds.
      7. ALT syringe onto injection cap.
      8. Instill ALT solution to fill CVC lumen. Remove empty syringe.
      9. Clamp catheter and allow antibiotic lock to dwell 4 hours minimum.  Longer dwell times are considered better.  Notify ID and the primary service if not able to dwell minimum of 4 hours per 24 hour period.
  • Label the CVC lumen that has the lock instilled in it: “ DO NOT USE- Antibiotic Lock In Place”
  • in APeX which line and/or lumen has an antibiotic lock; lumen color/locality should be entered as a comment in the lock administration on the eMAR.
  • Attach a pre-filled normal saline syringe and flush CVC with 10mL of normal saline; then remove and discard syringe.
  • Vigorously scrub the needleless connector for 10 seconds with alcohol pad and allow to dry for 10 seconds
    1. IF instilling a subsequent day/dose ALT, return to step a6.
    2. IF utilizing the lumen for an infusion, attach tubing per procedure.
    3. IF ALT therapy complete and no needed infusions, heparinize catheter per provider order.
  • Guideline Working Group

Antimicrobial Stewardship Program Lead Pharmacist(s): Steve Grapentine PharmD, BCPS, APP & Alex Hilts-Horeczko PharmD

Antimicrobial Stewardship Program Medical Director: Sarah Doernberg MD, MAS

Clinical Content Advisor: Kathy Yang PharmD, MPH

Clinical Nurse Specialist: Laura Griffith RN, MSN, AOCNS

Nursing Informatics: Craig Johnson RN-BC, MSN, FNP

Pharmacy Student: Sharon Xu Doctor of Pharmacy Candidate, 2021

 

  • Guideline History:

Initial Guideline Developed: 12/11/2020

Appendix C: Antibiotic Lock Recipes

 

Cefazolin 10 mg/mL + Heparin 10 mg/ml

 

Materials and Equipment

Syringes: 5 mL(1), 10 mL (2), 20 mL (1)

Needles: 19 to 21 gauge (1)

Miscellaneous: Alcohol wipes, labels, syringe cap

 

Pharmaceuticals

Cefazolin Powder for Injection 500mg vial (1)

Heparin Lock Flush Injection 100 units/mL Pre-Filled Syringe (1) Bacteriostatic Normal Saline vial (1)

 

Compounding

1. Clean all surfaces with 70% isopropyl alcohol

2. Assemble all pharmaceuticals and materials

 

To prepare 10 mg/mL

antibiotic lock solution

 

TW O MILLILITER LOCK SOLUTION

  1. Reconstitute 500mg with 4.5 a of 100mg/mL
  2. Add 1 of 100mg/mL to 20
  3. Add 8 NS the 20 a
  4. Add 1 100 units/mL to the 20mL
  5.  
  6. 2 mL of Cefazolin -Heparin solution to a 10 mL syringe
  7.  

 

FIVE MILLILITER LOCK SOLUTION

  1. Reconstitute 500mg with 4.5Bacteriostatic a of 100mg/mL
  2. Add 1 of 100mg/mLto 20
  3. Add 8 NS the 20 a
  4. Add 1 100 units/mL(100 the 20mL
  5.  
  6. 5 mL of Cefazolin-Heparin solution to a 10 mL syringe

Label with 30 hour expiration date

Beyond Use Dating

30 hours at room temperature, prepare on demand

Stability

  • stability of heparin (10 units/mL) was evaluated (per change in APTT) by combining cefazolin 10 mg/mL
  • in the dark at 4˚C and 37˚C
  • No clinicallysignificant on heparin andsolutionswere compatible for14

 

Reference(s)

Robinson, J. L., Tawfik, G., Saxinger, L., Stang, L., Etches, W., & Lee, B. (2005). Stability of heparin and physical compatibility of heparin/antibiotic solutions in concentrations appropriate for antibiotic lock therapy. Journal of Antimicrobial Chemotherapy, 56(5), 951–953. https://doi.org/10.1093/jac/dki311

 

 

 

 

Ceftazidime 10 mg/mL + Heparin 10 mg/ml

 

Materials and Equipment

Syringes: 5 mL(1), 10 mL (2), 20 mL (1)

Needles: 19 to 21 gauge (1)

Miscellaneous: Alcohol wipes, labels, syringe cap

Pharmaceuticals

Ceftazidime Powder for Injection 500mg vial (1)

Heparin Lock Flush Injection 100 units/mL Pre-Filled Syringe (1) Bacteriostatic Normal Saline vial (1)

Compounding

  1. Clean all surfaces with 70% isopropyl alcohol

Assemble all pharmaceuticals and materials

To prepare 10 mg/mL

antibiotic lock solution

 

TWO MILLILITER LOCK SOLUTION

  1. Reconstitute 500 mg Ceftazidime vial with 5.3 mL Bacteriostatic NS. This results in a concentration of 100 mg/mL
  2. Add 1 mL of Ceftazidime 100 mg/mL (100 mg) to the 20 mL syringe
  3. Add 8 mL Bacteriostatic NS to the 20 mL syringe. Attach a “universal syringe tip adapter”
  4. Add 1 mL Heparin 100 units/mL (100 units) to the 20 mL syringe
  5. Agitate solution
  6. Transfer 2 mL of Ceftazidime-Heparin solution to a 10 mL syringe
  7. Label with 30-hour expiration date

 

FIVE MILLILITER LOCK SOLUTION

  1. Reconstitute 500 mg Ceftazidime vial with 5.3 mL Bacteriostatic NS. This results in a concentration of 100 mg/mL
  2. Add 1 mL of Ceftazidime 100 mg/mL (100 mg) to the 20 mL syringe
  3. Add 8 mL Bacteriostatic NS to the 20 mL syringe. Attach a “universal syringe tip adapter”
  4. Add 1 mL Heparin 100 units/mL (100 units) to the 20 mL syringe
  5. Agitate solution
  6. Transfer 5 mL of Ceftazidime-Heparin solution to a 10 mL syringe

Label with 30-hour expiration date

 

Beyond Use Date

30 hours at room temperature, prepare on demand

Stability

10mg/mL and heparin 10 units/mL at UCSF Medical Center Hospital Pharmacy

 

 

 

 

Ceftazidime 10 mg/mL

Heparin 10 units/mL

Day

0

1

3

7

37˚C

C

C

C

C

25˚C

C

C

C

C

 

 

Reference(s)

 

 

 

Gentamicin 2.5 mg/mL + Sodium Citrate 40 mg/ml (4%)

 

Materials and Equipment

Syringes: 5 mL(1), 10 mL (2)

Miscellaneous: Alcohol wipes, labels, syringe cap

Pharmaceuticals

Gentamicin 40 mg/mL (2 mL vial) (1)

Sodium Citrate 4% (40 mg/mL) (3 mL syringe) (2)

Compounding

  1. Clean all surfaces with 70% isopropyl alcohol

Assemble all pharmaceuticals and materials

To prepare 2 mg/mL

antibiotic lock solution

 

 

 

 

To prepare 5 mg/mL antibiotic lock solution

 

TW O MILLILITER LOCK SOLUTION

  1. a “universal syringe tip adapter” to Sodium Citrate 4% syringe. Attach a 5 mL syringe. Add 2.8 mL Sodium Citrate 4% into the 5 mL syringe.
  2. Add 0.2 mto the 5 mL syringe
  3. Cap and toget.
  4. 2 mL of Gentamicin-Sodium Citrate solution to a 10 mL syringe.
  5.  

 

FIVE MILLILITER LOCK SOLUTION

  1. a “universal syringe tip adapter” to Sodium Citrate 4% syringe. Attach a 10 mL syringe. Add 5.6 mL Sodium Citrate 4% into 10 mL syringe.
  2. Add 0.4 mL of Gentamicin 40 mg/mL to the 10mL
  3. Cap and to get
  4. 5 mL of Gentamicin-Sodium Citrate solution to a 10 mL syringe.
  5.  

 

Beyond Use Date

30 hours at room temperature, prepare on demand

Stability

  • The stability of the gentamicin 2.5 mg/mL + Sodium Citrate 40 mg/ml combination were assessed by HPLC.
  • in a plastic bin with an opaque, snug-fitting lid.
  • Results indicate stability for at least 112 days at room temperature.

 

Reference(s)

Cote D, Lok CE, Battistella M et al. Stability of Trisodium Citrate and Gentamicin Solution for Catheter Locks after Storage in Plastic Syringes at Room Temperature. Can J Hosp Pharm. 2010; 63:304-11.

 

 

Linezolid 1 mg/mL + Heparin 10 mg/ml

 

Materials and Equipment

Syringes: 5 mL(1), 10 mL (2), 20 mL (1)

Needles: 19 to 21 gauge (1)

Miscellaneous: Alcohol wipes, labels, syringe cap

 

Pharmaceuticals

Linezolid Pre-made Infusion 200mg/100mL bag (1)

Heparin Lock Flush Injection 100 units/mL Pre-Filled Syringe (1) Bacteriostatic Normal Saline vial (1)

Compounding

1. Clean all surfaces with 70% isopropyl alcohol

2. Assemble all pharmaceuticals and materials

 

To prepare 1 mg/mL

antibiotic lock solution

 

TWO MILLILITER LOCK SOLUTION

  1. Add 5 mL Linezolid 2 mg/mL (10 mg) to a 20 mL syringe
  2. Add 4 mL Bacteriostatic NS to the 20 mL syringe. Attach a “universal syringe tip adapter”
  3. Add 1 mL Heparin 100 units/mL (100 units) to the 20 mL syringe
  4. Agitate solution
  5. Transfer 2 mL of Linezolid-Heparin solution to a 10 mL syringe
  6. Label with 30-hour expiration date

 

FIVE MILLILITER LOCK SOLUTION

  1. Add 5 mL Linezolid 2 mg/mL (10 mg) to a 20 mL syringe
  2. Add 4 mL Bacteriostatic NS to the 20 mL syringe. Attach a “universal syringe tip adapter”
  3. Add 1 mL Heparin 100 units/mL (100 units) to the 20 mL syringe
  4. Agitate solution
  5. Transfer 5 mL of Linezolid-Heparin solution to a 10 mL syringe

Label with 30-hour expiration date

 

Beyond Use Date

30 hours at room temperature, prepare on demand

Stability

  • Linezolid (2 mg/mL) initially evaluated alone and subsequently evaluated in combination of heparin at a concentration of 10 units/mL for 72 hr. Incubated at 37°C
  • Stabilities of antimicrobials assessed by bioassay
  • Inclusion of heparin at a concentration of 10 units/mL did not impair activity of linezolid against the biofilm

 

Reference(s)

Curtin, J., Cormican, M., Fleming, G., Keelehan, J., & Colleran, E. (2003). Linezolid compared with eperezolid, vancomycin, and gentamicin in an in vitro model of antimicrobial lock therapy for Staphylococcus epidermidis central venous catheter-related biofilm infections. Antimicrobial Agents and Chemotherapy, 47(10), 3145–3148. https://doi.org/10.1128/AAC.47.10.3145-3148.2003

Droste, J. C., Jeraj, H. A., MacDonald, A., & Farrington, K. (2003). Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis. Journal of Antimicrobial Chemotherapy, 51(4), 849–855. https://doi.org/10.1093/jac/dkg179

 

 

Vancomycin 2 mg/mL + Heparin 10 mg/ml

 

Materials and Equipment

Syringes: 5 mL(1), 10 mL (2), 20 mL (1)

Needles: 19 to 21 gauge (1)

Miscellaneous: Alcohol wipes, labels, syringe cap

Pharmaceuticals

Vancomycin Powder for Injection 500mg vial (1)

Heparin Lock Flush Injection 100 units/mL Pre-Filled Syringe (1) Bacteriostatic Normal Saline vial (1)

Normal Saline 100mL bag (1)

Compounding

  1. Clean all surfaces with 70% isopropyl alcohol

Assemble all pharmaceuticals and materials

To prepare 2 mg/mL

antibiotic lock solution

 

TW O MILLITER LOCK SOLUTION

  1. Add 5 NS the 20 a
  2. Add 1 100 units/mLto the 20mL
  3. Cap and toget
  4. and waste 10 mL from NS 100 mL bag.
  5. Reconstitute 500mg with 10 bag andaddbacktobag. a of 5mg/mL.
  6. 4 mL of Vancomycin 5mg/mL (20 mg total) into a syringe.
  7. add 4 mL of Vancomycin 5 mg/mL (20 mg) to the 20 mL syringe with agitation.
  8. 2 mL of Vancomycin-Heparin solution to a 10 mL syringe.
  9.  

 

FIVE MILLITER LOCK SOLUTION

  1. Add 5 NS the 20 a
  2. Add 1 100 units/mL to 20mL
  3. Cap and to get
  4. and waste 10 mL from NS 100 mL bag.
  5. Reconstitute 500mg with 10bag andaddbacktobag. a of 5mg/mL.
  6. 4 mL of Vancomycin 5mg/mL (20 mg total) into a syringe.
  7. add 4 mL of Vancomycin 5 mg/mL (20 mg) to the 20 mL syringe with agitation.
  8. 5 mL of Vancomycin-Heparin solution to a 10 mL syringe.

Label with 30-hour expiration date.

Beyond Use Date

30 hours at room temperature, prepare on demand

Stability

  • stability of heparin (10 units/mL) was evaluated (per change in aPTT) by combining vancomycin 2.5 mg/mL.
  • in the dark at 4°Celsius and 37°Celsius
  • No clinicallysignificant on andsolutionswere compatible for14

 

Reference(s)

Robinson, J. L., Tawfik, G., Saxinger, L., Stang, L., Etches, W., & Lee, B. (2005). Stability of heparin and physical compatibility of heparin/antibiotic solutions in concentrations appropriate for antibiotic lock therapy. Journal of Antimicrobial Chemotherapy, 56(5), 951–953. https://doi.org/10.1093/jac/dki311

 

 

References

  • Bookstaver PB, Rokas KE, Norris LB, Edwards JM, Sherertz RJ. Stability and compatibility of antimicrobial lock solutions. Am J Health Syst Pharm. 2013;70(24):2185-98.
  • Bookstaver, B., & Justo, J. A. (2014). Antibiotic lock therapy: review of technique and logistical challenges. Infection and Drug Resistance, 343. https://doi.org/10.2147/idr.s51388
  • Carratalà J. Role of antibiotic prophylaxis for the prevention of intravascular catheter-related infection. Clin Microbiol Infect. 2001;7 Suppl 4:83-90.
  • Centers for Disease Control and Prevention. Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011. https://www.cdc.gov/hai/pdfs/bsi-guidelines-2011.pdf. Accessed June 8, 2018.
  • Cote D, Lok CE, Battistella M et al. Stability of Trisodium Citrate and Gentamicin Solution for Catheter Locks after Storage in Plastic Syringes at Room Temperature. Can J Hosp Pharm. 2010; 63:304-11.
  • Haimi-Cohen Y, Husain N, Meenan J, et al. Vancomycin and ceftazidime bioactivities persist for at least 2 weeks in the lumen in ports: simplifying treatment of port-associated bloodstream infections by using the antibiotic lock technique. Antimicrob Agents Chemother. 2001;45(5):1565-7.
  • Justo JA, Bookstaver PB. Antibiotic lock therapy: review of technique and logistical challenges. Infect Drug Resist. 2014;7:343-63.
  • LA, Allon M, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infections 2009 update. Clinical Infectious Diseases 2009;49:1-45.
  • M. University of Wisconsin Hospital and Clinics Guidelines for Anti-Infective Lock Solutions. Approved 1/2011.
  • Stanford Hospital and Clinics. Antibiotic Lock Therapy Guideline. Reviewed 01/2015.
  • Yokoyama H, Aoyama T, et al. The cause of polyurethane catheter cracking during constant infusion of etoposide (VP-16) injection. Yakagaku Zasshi. 1998;118:581-