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. 2014 Dec 12;7:343–363. doi: 10.2147/IDR.S51388

Table 2.

Summary of available in vitro and in vivo data on antibiotic lock solutions

Antibiotic class/agent Antibiotic concentrations Additives and concentrations Stability comments Dwell time/duration (if applicable) Type of investigation(s)
Penicillins
Penicillin G25 50,000 units/mL Heparin 2,500 and 5,000 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions; duration 2–3 weeks with systemic antibiotics Case report
Ampicillin24, 84, 85 10 mg/mL Heparin 10 and 5,000 units/mL Physically stable (visual confirmation) for 14 days at 4°C and 37°C; yellow color reported at day 3; heparin stable for 14 days based on aPTT measures In vitro bioactivity study
5 mg/mL No additives Case report
2 mg/mL Heparin 10 units/mL Visual confirmation of physical compatibility Dwell time up to 6 hours, solution aspirated then replaced to target continuous lock In vivo study
Amoxicillin25 5 mg/mL Heparin 2,500 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions; duration 2–3 weeks with systemic antibiotics Single case report
Piperacillin2426 10, 20, 40 mg/mL Heparin 10 and 5,000 units/mL Physically stable (visual confirmation) for 14 days at 4°C and 37°C; yellow color reported at day 3 with piperacillin 40 mg/mL; heparin stable for 14 days based on aPTT measures with piperacillin 40 mg/mL In vitro bioactivity study
100 mg/mL Heparin 400 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions; duration 2–3 weeks with systemic antibiotics Case report
Piperacillin/tazobactam27 10 mg/mL Heparin 100 units/mL Visual confirmation of physical compatibility Two case reports; dwell time of a minimum of 12 hours per day; duration of 10 days with systemic antibiotics
Ticarcillin/clavulanate23 0.5 mg/mL Heparin 100 units/mL Bioassay stability sampling confirmed < 10% loss of activity at 10 days at 25°C and 37°C in polystyrene test tubes; addition of susceptible bacteria had no impact on stability In vitro bioassay stability study
Nafcillin86 83.3 mg/mL, 166.6 mg/mL No additives Visual confirmation of physical compatibility Dwell time of 12 hours daily; average duration 8 days Case series (6 reports)
Cloxacillin87 100 mg/mL Heparin 1,000 units/mL Visual confirmation of physical compatibility Dwell time up to 96 hours between HD sessions In vivo study
Mezlocillin88 2 mg/mL No additives Visual confirmation of physical compatibility Dwell time 12–24 hours; duration 10–14 days Case series (one report)
Flucloxacillin38 20 mg/mL Heparin 10–10,000 units/mL Visual precipitation testing grid; authors comment that “low-dose heparin” showed precipitation at 48 hours at 25°C and 37°C; combination with heparin 4,000 units/mL stable for 72 hours In vitro bioactivity study
Cephalosporins
Cefazolin20,21,23,24,45,84,8996 10 mg/mL Heparin 10 and 5,000 units/mL Physically stable (visual confirmation) for 14 days at 4°C; and 37°C; yellow color reported; heparin stable for 14 days based on aPTT measures In vitro bioactivity study
10 mg/mL Heparin 5,000 units/mL < 10% change in absorbance at 72 hours in glass tubes; 27.3% change in absorbance at 72 hours in polyurethane catheter In vitro stability study
5 mg/mL Gentamicin 5 mg/mL and heparin 1,000 and 5,000 units/mL Visual confirmation of physical compatibility; combination with heparin 5,000 units/mL confirmed to 72 hours at 37°C – a haze reported when prepared at room temperature within 30 minutes In vivo study; in vitro model of CRSBI
5 mg/mL TPA 1 mg/mL Visual confirmation of physical compatibility up to 48 hours In vivo study
5 mg/mL Heparin 5,000 units/mL Visual confirmation of physical compatibility up to 72 hours Dwell time up to 72 hours between HD sessions; duration up to 2 weeks In vitro and animal models of CRBSI; in vivo study
5 mg/mL Gentamicin 1 mg/mL and heparin 2,500 units/mL Visual confirmation of physical compatibility up to 72 hours at 25°C and 37°C Dwell time up to 72 hours between HD sessions In vivo study; animal model of CRSBI
5 mg/mL Heparin 2,500 units/mL Visual confirmation of physical compatibility up to 72 hours In vivo study
5 mg/mL Heparin 10 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions In vivo study
0.5 mg/mL Heparin 100 units/mL Bioassay stability sampling confirmed ≤ 10% loss at 10 days at 25°C and 37°C in polystyrene test tubes; addition of susceptible bacteria had no impact on stability Dwell time up to 72 hours between HD sessions In vitro bioassay stability study
Ceftazidime2123,86,95,97,98 0.5 mg/mL Heparin 100 units/mL Bioassay stability sampling confirmed < 10% loss of activity at 3 days at 25°C and 37°C in polystyrene test tubes; 30%–38% loss of activity at 7 days at 37°C Dwell time of 8–12 hours/day; duration 7–14 days In vitro bioassay stability study; in vivo study
2 mg/mL Heparin 100 units/mL Concentrations from aspirated lock after ≤ 15 days and ≤21 days in situ remained 234 μg/mL and 110 μg/mL, respectively Continuous dwell times of 2–34 days (median =17 days) In vivo study with residual antibiotic concentration analysis
2.5 mg/mL Vancomycin 2.5 mg/mL and heparin 2,500 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions In vivo study
5 mg/mL Heparin 2,500 units/mL Visual confirmation of physical compatibility; authors state up to 72 hours at 37°C (unpublished) Dwell time up to 72 hours between HD sessions In vivo study
10 mg/mL Heparin 5,000 units/mL 10.6%–12.9% change in absorbance at 48 and 72 hours at 37°C in glass tubes, respectively; 31.9%–40.2% change at 48 and 72 hours in polyurethane catheters, respectively In vitro stability study
83.3 mg/mL, 166.6 mg/mL, and 333 mg/mL No additives Dwell time of 12 hours daily; average duration of 8 days Case series
Ceftriaxone86 83.3 mg/mL, 166.6 mg/mL No additives Dwell time of 12 hours daily; average duration of 8 days Case series
Cefotaxime99104 10 mg/mL Heparin 5,000 units/mL Visual confirmation of physical compatibility; one study stored lock solutions under refrigeration prior to instillation in HD port. Chemical/physical stability confirmed at 4°C; > 10% degradation at 24 hours at 27°C and 40°C Dwell time up to 72 hours between HD sessions In vivo study; in vitro stability study
Carbapenems
Imipenem/cilastatin29 50 mg/mL Heparin Visual confirmation of physical compatibility In vivo study
Fluoroquinolones
Ciprofloxacin23,29,38,68,95,105,106 0.100 mg/mL Heparin 5,000 units/mL (reported as 5% heparin sodium) Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions; duration of 15 days In vivo study
0.125 mg/mL Heparin 100 units/mL Bioassay stability sampling confirmed no loss of activity at 10 days at 25°C and 37°C in polystyrene test tubes; addition of susceptible bacteria had no impact on stability; ciprofloxacin concentrations >0.125 μg/mL formed visual precipitation with heparin In vitro bioassay stability study
0.1–1 mg/mL Heparin 10–10,000 units/mL Visual stability at 7 days at 25°C and 37°C in glass tubes confirmed for the following combinations: ciprofloxacin 0.1 mg/mL + heparin 10–10,000 units/mL; ciprofloxacin 0.2 mg/mL + heparin 1,000–10,000 units/mL; ciprofloxacin 0.4–0.6 mg/mL + heparin 5,000–10,000 units/mL In vitro stability study
0.1–1 mg/mL Teicoplanin 0.1–4 mg/mL + heparin 7–10,000 units/mL Visual stability at 7 days at 25°C and 37°C in glass tubes confirmed for the following combinations: teicoplanin 0.1 mg/mL + ciprofloxacin 0.1 mg/mL + heparin 7–10,000 units/mL; teicoplanin 0.2 mg/mL + ciprofloxacin 0.2 mg/mL + heparin 700–10,000 units/mL; teicoplanin 0.4–2.0 mg/mL + ciprofloxacin 0.4 mg/mL + heparin 3,500–10,000 units/mL; teicoplanin 4 mg/mL + ciprofloxacin 0.8 mg/mL + heparin 10,000 units/mL In vitro stability study
0.2–0.8 mg/mL Sodium citrate 22 g/L Authors report visual stability at 7 days at 25°C and 37°C in glass tubes In vitro stability study
0.4–0.6 mg/mL Teicoplanin 4 mg/mL + sodium citrate 22 g/L Visual stability confirmed at 7 days at 25°C and 37°C in glass tubes for ciprofloxacin 0.4 mg/mL in combination In vitro stability study
1 mg/mL Heparin 2,500 units/mL < 10% variability at 72 hours at 37°C in glass tubes In vitro bioassay stability study
2 mg/mL Heparin Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions In vivo study
10 mg/mL No additives < 10% variability at 10 days at 37°C in glass tubes In vitro bioassay stability study
10 mg/mL Heparin 5,000 units/mL Immediate precipitation In vitro stability study
Levofloxacin27,47 0.05, 3.2 mg/mL Clarithromycin 200 mg/mL ± heparin 1,000 units/mL Visual confirmation of compatibility at 96 hours at 37°C In vitro stability and bioactivity study
5 mg/mL Heparin 100 units/mL Precipitation noted; levofloxacin 5 mg/mL used without additive Dwell time minimum of 12 hours/day, changed daily; Duration of 7–14 days Case series
Aminoglycosides
Amikacin18,19,38,40,65,66,68,70,88,107109 0.02–4 mg/mL Teicoplanin 0.02–10 mg/mL ± heparin 7–10,000 units/mL Visual stability at 7 days at 25°C and 37°C in glass tubes confirmed for the following combinations: teicoplanin 0.02–0.5 mg/mL + amikacin 0.02–0.05 mg/mL; teicoplanin 0.02–2 mg/mL + amikacin 0.02–3 mg/mL + heparin 700–10,000 units/mL; teicoplanin 4–10 mg/mL + amikacin 0.02–3 mg/mL + heparin 3,000–10,000 units/mL In vitro stability study
1 mg/mL No additives Dwell time of 24 hours, changed daily; duration of 5 days In vivo study
1.5 mg/mL No additives Bioactivity reported by authors up to 14 days stored at 4°C Dwell time 12 hours/day; changed daily; duration of 14 days In vivo study
2 mg/mL No additives Dwell time of 12 hours/day; changed every 12 hours; duration 10–14 days Case report
2 mg/mL Heparin 20 units/mL Visual confirmation of physical compatibility Dwell time minimum of 72 hours; duration of 3–14 days In vivo study
5 mg/mL No additives Dwell time 12–24 hours; duration 11 days Case report
5 mg/mL Vancomycin 5 mg/mL + heparin 5,000 units/mL Visual confirmation of physical compatibility Dwell time of 72 hours; duration of 3 days In vivo study
10 mg/mL Heparin 5,000 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions Case report
20 mg/mL No additives Dwell time 12–24 hours; duration 3 days In vivo study
40 mg/mL Heparin 100 units/mL Visual confirmation of physical compatibility Continuous dwell changed every 8 hours; duration of 14 days In vivo study
Gentamicina,34,38,45,48,63,95,110,111 0.1 mg/mL Heparin 5,000 units/mL At 4°C, compatible and stable for up to 4 weeks; confirmed via particle-enhanced turbidimetric inhibition immunoassay In vitro stability study
0.32 mg/mL Citrate 40 mg/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions In vivo study
0.02–2 mg/mL Teicoplanin 0.02–2 mg/mL + heparin 7–10,000 units/mL At 25°C and 37°C, gentamicin 0.02 and teicoplanin 0.02 compatible at all heparin concentrations; gentamicin 0.2–1 mg/mL, teicoplanin 0.2–1 mg/mL + heparin 3,500–10,000 units/mL compatible for 7 days In vitro stability and bioactivity study
1 mg/mL Heparin 2,500 units/mL + vancomycin 2.5 mg/mL + cefazolin 5 mg/mL Compatibility confirmed at 37°C for 72 hours Dwell time up to 72 hours between HD sessions In vivo study
2, 4 mg/mL Teicoplanin 4 mg/mL + citrate 22 g/dL Gentamicin 2 mg/mL + teicoplanin 4 mg/mL + citrate compatible at 37°C for 7 days In vitro stability study
2.5 mg/mL Heparin 10 units/mL Visual confirmation of physical compatibility Dwell time 12–24 hours; duration up to 15 days Case series
2.5 mg/mL Citrate 40 mg/mL At 37°C, no decrease in gentamicin or citrate concentration at 96 hours; at room temperature, 100% of gentamicin and 101.3% citrate retained for 112 days In vitro stability studies
3 mg/mL Daptomycin 1 mg/mL + citrate 28 mg/mL + LR Refer to Daptomycin section in this table In vitro stability study
5 mg/mL EDTA 30 mg/mL Visual confirmation of physical compatibility for 72 hours in glass tubes at 25°C and 37°C Dwell time 12–24 hours In vitro bioactivity study; animal model
5 mg/mL Heparin 10 units/mL Visual confirmation of physical compatibility In vitro bioactivity study
5 mg/mL Heparin 1,000 units/mL Visual confirmation of physical compatibility Dwell time 12–24 hours; duration up to 15 days Case series; in vivo study
5 mg/mL Heparin 5,000 units/mL 92% of gentamicin concentration retained at 72 hours Dwell time 12–24 hours; duration up to 15 days In vitro stability study
5 mg/mL Vancomycin 10 mg/mL+ heparin 10–5,000 units/mL Mild haziness on preparation, dissipated with time and warming Dwell time 12–24 hours; duration up to 15 days Case series
Tobramycin20,34,36,112 2.4 mg/mL Sodium citrate 40 mg/mL Stability and compatibility confirmed at 48 hours at 23°C and 37°C In vitro stability study
5 mg/mL TPA 0.875 mg/mL Stability and compatibility confirmed at 12 hours room temperature Dwell times of 72 hours with HD sessions In vivo study; case series
5 mg/mL TPA 1 mg/mL Visual confirmation of physical compatibility up to 48 hours In vivo study
Glycopeptides
Vancomycina,20,22,23,39,40,46,70,95,104,106,107,110,113121 0.025 mg/mL Heparin 9.75 units/mL At 4°C or room temperature, vancomycin concentrations stable for 40 days Dwell times variable in neonates In vitro bioassay stability study; in vivo study
0.025 mg/mL Heparin 100 units/mL At 4°C, vancomycin concentration stable for 14 days; at 37°C, concentration reduced by 15%–37% at 24 hours In vitro stability study; in vivo study
0.025 mg/mL Heparin 5,000 units/mL At 4°C and 27°C, compatible and stable for 72 hours; at 40°C, 81 % of vancomycin concentration retained at 72 hours Dwell times variable in adult cancer patients In vitro stability study; in vivo study
0.1 mg/mL Heparin 5,000 units/mL At 4°C, compatible and stable for up to 4 weeks In vitro stability study
0.1 mg/mL Colistin 0.1 mg/mL + heparin 100 units/mL Refer to Colistin section in this table In vitro stability study
0.5 mg/mL Heparin 100 units/mL Bioassay stability sampling confirmed < 10% loss of activity at 10 days at 25°C and 37°C in polystyrene test tubes; addition of susceptible bacteria and no impact on stability In vitro bioassay stability study
1 mg/mL No additives Bioactivity reported by authors up to 14 days stored at 4°C Dwell time 12 hours/day; changed daily; duration of 14 days In vivo study
1 mg/mL Citrate 40 mg/mL At 4°C, RT, or 37°C, >92% of vancomycin concentration at 72 hours with storage in polyvinyl chloride syringes of HD catheters In vitro stability study
2 mg/mL Heparin 20 units/mL Visual confirmation of compatibility; prepared every 3 days and stored at 4°C Dwell times of 8–12 hours per day; duration of 14 days In vivo study
2 mg/mL Heparin 100 units/mL Vancomycin concentration of ≥0.130 mg/mL retained for up to 28 days Dwell time 4–28 days in ports of patients In vivo studies
2 mg/mL Heparin 2,500 units/mL At 37°C, stable for at least 72 hours and physically compatible; at 37°C, >90% of vancomycin concentration over 72 hours In vitro stability studies
2 mg/mL Citrate 22 mg/mL Initial precipitation, but no precipitation noted after 10 minutes of incubation at 37°C; >90% of vancomycin concentration over 72 hours In vitro stability study
2 mg/mL Citrate 40 mg/mL Physically compatible; at 37°C, >90% of vancomycin concentration retained over 72 hours In vitro stability study
2.5 mg/mL Heparin 2.5 units/mL Decrease in vancomycin concentration gradient from proximal to distal segments of dialysis catheter at 48 hours Dwell time 48 hours in HD catheters In vivo study with drug concentration analysis
3 mg/mL No additives In vivo study
3 mg/mL Citrate 40 mg/mL At 4°C, RT, or 37°C, >92% of vancomycin concentration at 72 hours with storage in polyvinyl chloride syringes of HD catheters In vitro stability study
5 mg/mL TPA 1 mg/mL Visual confirmation of physical compatibility up to 48 hours In vivo study
5 mg/mL No additives Dwell times of 48 hours; duration of 7 days In vivo study
5 mg/mL Heparin 2,500 units/mL At 37°C, >90% of vancomycin concentration at 72 hours and physically compatible In vitro stability study
5 mg/mL Citrate 22 mg/mL Initial precipitation, but no precipitation noted after 10 minutes of incubation at 37°C; >90% of vancomycin concentration over 72 hours In vitro stability study
5 mg/mL Citrate 40 mg/mL Physically compatible; at 37°C, >90% of vancomycin concentration retained over 72 hours In vitro stability study
10 mg/mL Heparin 5,000 units/mL In glass test tubes stored at 37°C, no change in vancomycin concentration over 72 hours; in CVCs, concentration decreased by 29.7% over 72 hours In vitro stability study; in vivo study
10 mg/mL Gentamicin 8 mg/mL + heparin 5,000 units/mL Visual confirmation of physical compatibility Dwell times up to 72 hours between HD sessions; duration of 2 weeks In vivo study
Teicoplanin38,122,123 0.02–10 mg/mL Heparin 10–10,000 units/mL Visual compatibility confirmed at 7 days at 25°C and 37°C in glass tubes In vitro stability study
0.1–4.0 mg/mL Ciprofloxacin 0.1–1 mg/mL + heparin 7–10,000 units/mL See ciprofloxacin section In vitro stability study
0.02–2.0 mg/mL Gentamicin 0.02–2 mg/mL + heparin 7–10,000 units/mL Refer to Gentamicin section in this table In vitro stability study
0.02–10 mg/mL Amikacin 0.02–4 mg/mL + heparin 7–10,000 units/mL Refer to Amikacin section in this table In vitro stability study
4 mg/mL Ciprofloxacin 0.4–0.6 mg/mL + sodium citrate 22 mg/mL Refer to Ciprofloxacin section in this table In vitro stability study
4 mg/mL Gentamicin 2–4 mg/mL + sodium citrate 22 mg/mL Refer to Gentamicin section in this table In vitro stability study
10 mg/mL Heparin 5,000 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions; duration of 21 days In vivo study
Telavancin39 2, 5 mg/mL Heparin 2,500 units/mL Physical and chemical stability at 72 hours at 37°C; aPTT increased in 5 mg/mL solution
2, 5 mg/mL Citrate 22 mg/mL, 0 mg/mL Physical and chemical stability at 72 hours at 37°C In vitro stability study
Oxazolidinones
Linezolid34,37,38,113 0.2–1.92 mg/mL Heparin 10–10,000 units/mL Visual compatibility confirmed at 7 days at 25°C and 37°C in glass tubes In vitro stability study
1 mg/mL Citrate 20 mg/mL Confirmation of physical stability based on visual changes, absorbance, and pH for 48 hours at 23°C and 37°C in glass tubes In vitro stability study
2 mg/mL Heparin 100 units/mL Visual confirmation of physical compatibility Dwell time of 8 hours; duration of 20 days Case report
2 mg/mL Heparin 2,000 units/mL Visual confirmation of physical compatibility Dwell time up to 72 hours between HD sessions In vivo study
Lipopeptides
Daptomycin34,45,64,124127 1 mg/mL Heparin 5,000 units/mL (reconstituted in 0.9% NS and LR) Visual compatibility confirmed at 72 hours at 25°C and 37°C in glass tubes In vitro bioactivity study
1 mg/mL Heparin 100–1,000 units/mL Visual compatibility confirmed for preparation Dwell times 12–24 hours; duration up to 15 days In vivo study
1 mg/mL Gentamicin 3 mg/mL + citrate 28 mg/mL + LR At 25°C, 90.7% and 86.7% of daptomycin concentration retained at 48 and 72 hours, respectively; 95.2% of gentamicin concentration retained at 96 hours In vitro stability study
2.5 mg/mL Ethanol 25% Visual confirmation of physical compatibility In vitro bioactivity study
5 mg/mL Heparin 100 units/mL (reconstituted in LR) <5% decrease in daptomycin and heparin concentrations at 14 days at 4°C and −20°C in polypropylene syringes In vitro stability study; in vivo study
5 mg/mL Citrate 4% (supplemented with calcium chloride 50 μg/mL) Confirmation of physical stability based on visual changes, absorbance, and pH for 48 hours at 23°C and 37°C in glass tubes In vitro stability study
5 mg/mL, 25 mg/mL Heparin 5, 5,000, 10,000 units/mL (reconstituted in LR) < 10% decrease in daptomycin concentration at 24 hours at 37°C In vitro bioactivity and stability study; in vivo study
Tetracyclines
Minocycline4042,69,70,128,129 0.2 mg/mL Bioactivity reported by authors up to 4 days stored at 4°C Dwell time 12 hours/day; changed daily; duration of 14 days In vivo study
2–3 mg/mL EDTA 30 mg/mL ± ethanol 25% Visual compatibility confirmed Dwell times up to 7 days used In vitro bioactivity study; in vivo study
Glycylcyclines
Tigecycline45,130,131 0.5 mg/mL EDTA 30 mg/mL Visual compatibility confirmed at 48 hours at 25°C and 37°C in glass tubes; color change detected after 48 hours In vitro bioactivity study
1 mg/mL NAC 80 mg/mL + heparin 2,000 units/mL (heparin 100 units/mL in single case report) Visual compatibility confirmed; samples stored at −21°C until use Dwell times 12–72 hours; duration 14 days In vivo study; case report
Folate antagonists
Sulfamethoxazole/trimethroprim27,128 10, 16 mg/mL (based on TMP component) Heparin 100 units/mL Visual confirmation of physical compatibility for up to 14 days (16 mg/mL solution) In vivo study
Trimethoprim128,132 5, 10 mg/mL EDTA 30 mg/mL + ethanol 25% (referred to as “B-lock”) Visual confirmation of physical compatibility In vitro bioactivity study
Polymyxins
Colistin46,47 0.1 mg/mL Vancomycin 0.1 mg/mL + heparin 100 units/mL Compatibility and stability confirmed; < 10% degradation at 60 days at 4°C and 25°C; vancomycin had ~25% decrease in concentrations after day 15 at room temperature In vitro stability study
0.8 mg/mL Clarithromycin 200 mg/mL ± heparin 1,000 units/mL Visual confirmation of physical compatibility at 96 hours In vitro bioactivity study

Note:

a

Several published reports of gentamicin and vancomycin were not included in the table due to duplication of concentrations.

Abbreviations: aPTT, activated partial thromboplastin time; CRBSI, catheter-related bloodstream infection; CVC, central venous catheter; EDTA, ethylenediaminetetraacetic acid; HD, hemodialysis; LR, lactated ringer's solution; NAC, N-acetylcysteine; NS, normal saline; RT, room temperature; TPA, tissue plasminogen activator; TMP, trimethoprim.