Antibiotic lock therapy: review of technique and logistical challenges

Figures & data

Table 1 Summary of biofilm penetration for select antibiotics

Antibiotic class/agent	Microorganism	Extent of penetration	Rate of penetration	Reference
Fluoroquinolones
Ciprofloxacin	Bacillus cereus, Pseudomonas fluorescens	100%	NR	^Citation10
	Pseudomonas aeruginosa	100%	Rapid	^Citation74
	P. aeruginosa	25%–50%	Rapid	^Citation75
	Klebsiella pneumoniae	80%–100%	Rapid	^Citation11
	Staphylococcus aureus, Staphylococcus epidermidis	86%–100%	NR	^Citation76
Levofloxacin	P. aeruginosa	100%	Rapid	^Citation75
Rifamycins
Rifampin	S. epidermidis	79% to >90%	Rapid	^Citation77,Citation78
Oxazolidinones
Linezolid	S. epidermidis	~100%a	Rapid	^Citation79
Lipopeptides
Daptomycin	S. epidermidis	≥100%b	Rapid	^Citation80
Tetracyclines
Tetracycline	B. cereus, P. fluorescens	88%–93%	NR	^Citation10
Macrolides
Erythromycin	B. cereus, P. fluorescens	72%–86%	NR	^Citation10
	S. epidermidis	45%–93%	Variable/slow	^Citation81
Beta-lactams
Ampicillin	K. pneumoniae (beta-lactamase positive)	0%	NA	^Citation11
	K. pneumoniae (beta-lactamase negative)	80%–100%	Rapid	^Citation11
Oxacillin	S. aureus, S. epidermidis	<70%	NR	^Citation76
Piperacillin	P. aeruginosa	50%–100%	Rapid	^Citation75
	P. aeruginosa	0%–15%	NR	^Citation82
Cefotaxime	S. aureus, S. epidermidis	68%–70%	NR	^Citation76
Imipenem	P. aeruginosa	50%–100%	Rapid	^Citation75
Glycopeptides
Vancomycin	S. aureus, S. epidermidis	<70%	NR	^Citation76
	S. epidermidis	Adequatec	Slow	^Citation77,Citation83
	S. aureus	Adequateb,d	Slow	^Citation9
Aminoglycosides
Streptomycin	B. cereus, P. fluorescens	0%–60%	NR	^Citation10
Tobramycin	P. aeruginosa	40%	Slow	^Citation74
Gentamicin	P. aeruginosa	<25%	Slow	^Citation75
Amikacin	P. aeruginosa	<25%	Slow	^Citation75
	S. aureus, S. epidermidis	79%–98%	NR	^Citation76

Notes:

a Comparable penetration compared to isolates of planktonic cells

b measured as intensity of fluorescence using confocal microscopy or other methods

c vancomycin concentrations reportedly exceeded the minimal inhibitory concentrations and minimal bactericidal concentrations for tested isolates

d represents vancomycin concentrations from 15–45 μg/mL.

Abbreviations: NA, not applicable; NR, not reported.

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 G^Citation25	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
Ampicillin^Citation24, ^Citation84, ^Citation85	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
Amoxicillin^Citation25	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
Piperacillin^Citation24^–^Citation26	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/tazobactam^Citation27	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/clavulanate^Citation23	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
Nafcillin^Citation86	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)
Cloxacillin^Citation87	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
Mezlocillin^Citation88	2 mg/mL	No additives	Visual confirmation of physical compatibility	Dwell time 12–24 hours; duration 10–14 days	Case series (one report)
Flucloxacillin^Citation38	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
Cefazolin^Citation20,Citation21,Citation23,Citation24,Citation45,Citation84,Citation89^–^Citation96	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
Ceftazidime^Citation21^–^Citation23,Citation86,Citation95,Citation97,Citation98	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
Ceftriaxone^Citation86	83.3 mg/mL, 166.6 mg/mL	No additives		Dwell time of 12 hours daily; average duration of 8 days	Case series
Cefotaxime^Citation99^–^Citation104	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/cilastatin^Citation29	50 mg/mL	Heparin	Visual confirmation of physical compatibility		In vivo study
Fluoroquinolones
Ciprofloxacin^Citation23,Citation29,Citation38,Citation68,Citation95,Citation105,Citation106	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
Levofloxacin^Citation27,Citation47	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
Amikacin^Citation18,Citation19,Citation38,Citation40,Citation65,Citation66,Citation68,Citation70,Citation88,Citation107^–^Citation109	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,^Citation34,Citation38,Citation45,Citation48,Citation63,Citation95,Citation110,Citation111	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
Tobramycin^Citation20,Citation34,Citation36,Citation112	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,^Citation20,Citation22,Citation23,Citation39,Citation40,Citation46,Citation70,Citation95,Citation104,Citation106,Citation107,Citation110,Citation113^–^Citation121	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
Teicoplanin^Citation38,Citation122,Citation123	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
Telavancin^Citation39	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
Linezolid^Citation34,Citation37,Citation38,Citation113	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
Daptomycin^Citation34,Citation45,Citation64,Citation124^–^Citation127	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
Minocycline^Citation40^–^Citation42,Citation69,Citation70,Citation128,Citation129	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
Tigecycline^Citation45,Citation130,Citation131	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/trimethroprim^Citation27,Citation128	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
Trimethoprim^Citation128,Citation132	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
Colistin^Citation46,Citation47	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.

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