Table 3.
Antimicrobial locking solutions used for hemodialysis catheters
| Study | N | Methods | Standard Definition of Bloodstream Infection Used | Definition of Bloodstream Infection | Antimicrobial Locking Solution | Control | Outcome | Rate/1000 Catheter-Days | P Value | Concerns |
|---|---|---|---|---|---|---|---|---|---|---|
| Pervez et al. (52) | 36 | Prospective, randomized study | No | Fever or chills without an alternate source of infection | Gentamicin 20 mg/ml+citrate 4.67% | Heparin 1000 U/ml | Bloodstream infection | 0.62 versus 2.11 | N/A | Resistance not measured |
| Dogra et al. (53) | 83 | Double-blind, randomized trial | Yes | CDC/IDSA (10) | Gentamicin 27 mg/ml+citrate 1% | Heparin 5000 U/ml | Bloodstream infection | 0 0.3 versus 4.2 | <0.001 | Vestibular toxicity, resistance not measured |
| McIntyre et al. (54) | 50 | Prospective, randomized, controlled trial | Yes | CDC/IDSA (10) | Gentamicin 5 mg/ml+heparin 5000 U/ml | Heparin 5000 U/ml | Bloodstream infection | 0.3 versus 4 | 0.02 | Resistance not measured |
| Nori et al. (55) | 30 | Prospective, open-label, randomized, controlled trial | Yes | CDC/IDSA (10) | Gentamicin 4 mg/ml+citrate 3.13% | Heparin 5000 U/ml | Bloodstream infection | 0 versus 4 | 0.008 | Resistance not measured |
| Venditto et al. (56) | 265 | Prospective, observational trial | No | Two positive blood cultures from peripheral or catheter in a symptomatic patient with fever >38°C with no other apparent source of infection | Gentamicin (N/A)+heparin | Heparin (units N/A) | Bloodstream infection | 0.4 versus 2.9 | 0.06 | Resistance not measured |
| Landry et al. (57) | 1410 | Retrospective chart review after initiation of a unit protocol | Yes | CDC/IDSA (12) | Gentamicin 4 mg/ml+heparin 5000 U/ml | Historical controls before introduction of locks | Bloodstream infection | 0.83–1.2 versus 17.0 | N/A | 4 yr study, gentamicin resistance observed in 32%. Bloodstream infection (coagulase-negative staphylococci n=13, Enterococcus n=7, Streptococcus n=2, Staphylococcus aureus n=1) |
| Fernández-Gallego et al. (58) | 101 | Prospective, observational study | No | Clinical improvement after antibiotics in patients with a fever and with positive blood cultures taken from the circuit, excluding other possible infection sites | Gentamicin 5 mg/lumen (approximately 1.5 mg/ml)+heparin 100 U | None | Bloodstream infection and bacterial resistance to gentamicin | 0.11 | N/A | 7 yr study, no resistance for pathogens “normally sensitive to gentamicin”, two cases of MRSA resistant to gentamicin |
| Moran et al. (59) | 303 | Randomized, prospective, single-blinded, multicenter trial | No | Presence of a positive blood culture obtained from catheter, associated with fever or chills or hypotension | Gentamicin 0.32 mg/ml+citrate 4% | Heparin 1000 U/ml | Bloodstream infection | 0.28 versus 0.91 | 0.003 | 4.5 yr study, no change in gentamicin resistance |
| Moore et al. (60) | 555 | Prospective, multicenter, observational cohort study | Yes | CDC/IDSA (12) | Gentamicin 0.32 mg/ml+citrate 4% | Heparin 1000 U/ml | a) Bloodstream infection b) Mortality | a) 0.45 versus 1.68 b) 10% versus 18% HR 0.32 (0.14–0.75) | a) 0.001 b) 0.001 | 3 yr study, reduction in gentamicin resistance by approximately 50% (P=0.01) |
| Goh et al. (61) | 64 | Single-center, retrospective cohort study | Yes | NHSN (2) | a) Gentamicin 5 mg/lumen (approximately 1.5 mg/ml) + Heparin 1000 U/ml b) Gentamicin +Citrate | a) Heparin 1000 U/ml b) Heparin 1000 U/ml | Bloodstream infection | a) 0.66 versus 1.42 RR 0.46 (0.30 to 0.72) b) 0.16 versus 1.42 RR 0.11 (0.05 to 0.22) | 0.001 | Resistance not measured |
| Onder et al. (62) | 43 | Single-center, retrospective cohort study | No | Positive blood culture from the catheter with or without positive peripheral blood culture with systemic symptoms (fever, chills, vomiting, hypotension) and no other identified source of infection | Tobramycin 5 mg/dl+tissue plasminogen activator 1 mg/ml | Heparin 5000 U/ml | Bloodstream infection | 6.2 versus 16.8 | 0.2 | Resistance not measured |
| Bleyer et al. (63) | 60 | Single-center, double-blind, randomized, controlled trial | No | Catheter colonization plus a peripheral blood culture growing the same organism | Minocycline 3 mg/ml+EDTA 30 mg/ml | Heparin (dose N/A) | Bloodstream infection | 0 versus 0.47 | 0.35 | Resistance not measured |
| Campos et al. (64) | 204 | Multicenter, open-label, randomized, controlled trial | Yes | KDOQI and CDC (8,10) | Minocycline 3 mg/ml+EDTA 30 mg/ml | Heparin 5000 U/ml | Bloodstream infection | 1.1 versus 4.3 | 0.005 | Resistance not measured |
| Saxena and Panhotra (65) | 96 | Prospective, case-control study | Yes | CDC (9) | Cefotaxime 10 mg/ml+heparin 5000 U/ml | Heparin 5000 U/ml | Bloodstream infection | 1.65 versus 3.13 | N/A | Resistance not measured |
| Saxena et al. (66) | 113 | Single-center, double-blind, randomized, controlled trial | Yes | CDC (9) | Cefotaxime 10 mg/ml+heparin 5000 U/ml | Heparin 5000 U/ml | Bloodstream infection | 1.44 versus 3.15 | <0.001 | Resistance not measured |
| Al-Hwiesh and Abdul-Rahman (67) | 63 | Single-center, randomized, controlled trial | Yes | CDC (9) | Vancomycin 25 mg/ml+gentamicin 40 mg/ml+heparin5000 U/ml | Heparin 5000 U/ml | Bloodstream infection | 4.54 versus 13.11 | 0.05 | Resistance not measured |
| Kim et al. (68) | 120 | Single-center, double-blind, randomized, controlled trial | Yes | CDC (10) | Cefazolin 10 mg/ml+gentamicin 5 mg/ml+heparin 1000 U/ml | Heparin 1000 U/ml | Bloodstream infection | 0.44 versus 3.12 | 0.03 | Resistance not measured |
| Rijnders et al. (69) | 270 | Multicenter, open-label, evaluator-blinded, randomized, controlled trial | No | Clinical signs or symptoms of systemic infection and one of the following: positive blood culture in combination with temperature >38°C, temperature >37.5°C (during dialysis), rigors, chills, malaise, altered mental status, or hypotension unresponsive to fluids on dialysis | Trimethoprim 5 mg/ml+ethanol 25%+EDTA 3% | Heparin 5000 U/ml | Bloodstream infection | 0.09 versus 0.41 | <0.03 | Catheter dysfunction |
| Bueloni et al. (70) | 145 | Multicenter, open-label, nonrandomized trial | No | Presence of at least one of the signs or symptoms of infection, such as fever, tremors or hypotension without another apparent focus of infection, with a positive culture if one is performed | Cefazolin 12 mg/ml+gentamicin 7 mg/ml+heparin 500 U/ml | Taurolidine 1.35%+citrate 4%+heparin 500 U/ml | a) Bloodstream infection b) Catheter removal | a) 0.79 versus 1.1 b) 49% versus 53% | 0.01 0.85 | Significantly higher rate of MRSA exit-site infections with cefazolin+gentamin lock |
| Allon (71) | 50 | Prospective, case-control study | No | Positive peripheral blood cultures in a febrile patient | Taurolidine 1.35%+ citrate 4% | Heparin 5000 U/ml | Bloodstream infection | 0.6 versus 5.9 | <0.001 | Catheter dysfunction |
| Betjes and van Agteren (72) | 58 | Single-center, randomized, controlled trial | No | Symptomatic patient with a positive bacterial blood culture drawn from the dialysis catheter with no other apparent source of infection | Taurolidine 1.35%+ citrate 4% | Heparin 5000 U/ml | Bloodstream infection | 0 versus 2.1 | 0.05 | Catheter dysfunction |
| Solomon et al. (73) | 110 | Multicenter, double-blind, randomized, controlled trial | No | A single positive blood culture | Taurolidine 1.35%+ citrate 4% | Heparin 5000 U/ml | Bloodstream infection | 1.4 versus 2.4 | 0.1 | Catheter dysfunction |
| Solomon et al. (74) | 174 | Prospective, cohort study compared with historical controls | No | A single positive blood culture | Taurolidine 1.35%+citrate 4%+heparin 5000 U/ml | a) Heparin 5000 U/ml b) Taurolidine 1.35%+ Citrate 4% | a1) Bloodstream infection a2) First use of thrombolytic b1) Blood stream infection b2) First use of thrombolytic | a1) 1.33 versus 3.25 a2) RR 1.4 (0.5 to 3.9) b1) 1.33 versus 1.22 b2) RR 0.2 (0.06 to 0.5) | a1) <0.001 a2) 0.5 b1) <0.001 b2) <0.001 | Cost |
| Winnicki et al. (75) | 106 | Multicenter, randomized, controlled trial | No | A positive bacterial blood culture drawn from the dialysis catheter in a symptomatic patient with fever or chills associated with dialysis and no apparent other source of infection | Taurolidine 1.35%+citrate 4%+heparin 5000 U/ml twice a wk with taurolidine 1.35%+citrate 4%+urokinase 25,000 U once a wk | Citrate 4% | a) Bloodstream infection b) Catheter dysfunction | a) 0.67 versus 2.7 b) 18.7 versus 44.3 | 0.003 0.001 | Cost |
| Al-Ali et al. (76) | 164 | Multicenter, single-blinded, randomized, controlled trial | No | Same organism obtained from blood aspirated through the catheter hub and from blood sample obtained from peripheral vein with no other identifiable cause of infection | Taurolidine 1.35%+citrate 4%+heparin 5000 U/ml twice a wk with taurolidine 1.35%+citrate 4%+urokinase 25,000 U once a wk | Taurolidine 1.35%+citrate 4%+heparin 5000 U/ml three times a wk | a) Catheter removal for bloodstream infection b) Catheter removal for dysfunction c) Need for tissue plasminogen activator use | a) 0 versus 3 b) 1 versus 4 c) 5 versus 12 | 0.08 0.17 0.61 | Cost |
| Weijmer et al. (77) | 291 | Multicenter, double-blind, randomized, controlled trial | No | Fever or cold chills not during a dialysis treatment and at least one positive blood culture and no other obvious cause of infection | Trisodium citrate 30% | Heparin 5000 U/ml | Bloodstream infection | 1.1 versus 4.1 | <0.001 | —- |
| Winnett et al. (78) | 413 | Multicenter, case-control study | No | Fever and one positive blood culture result with no other obvious source of infection | Trisodium citrate 46.7% | Heparin 5000 U/ml | Bloodstream infection | 0.81 versus 2.13 | <0.001 | Not FDA approved, excessive overfill may result in death |
| Power et al. (79) | 232 | Single-center, randomized, controlled trial | No | Symptomatic febrile patient with positive blood cultures | Trisodium citrate 46.7% | Heparin 5000 U/ml | Bloodstream infection | 0.7 versus 0.7 | 0.9 | Lack of efficacy |
| Venditto et al. (56) | 265 | Single-center, prospective, cohort study compared with historical controls | Yes | CDC (10) | Trisodium citrate 46% | Heparin (n/a) | Bloodstream infection | 3.4 versus 2.9 | 0.6 | Lack of efficacy |
| Correa Barcellos et al. (80) | 464 | Single-center, double-blind, randomized, controlled trial | Yes | CDC (10) | Trisodium citrate 30% | Heparin 5000 U/ml | Bloodstream infection | Rate ratio 1.53 (95% CI, 0.9–2.58) | — | Lack of efficacy |
| Hemmelgarn et al. (81) | 225 | Multicenter, double-blind, randomized, controlled trial | Yes | Health Canadian 1997 Guidelines (7) | Recombinant tissue plasminogen activator once a wk +heparin 5000 U/ml twice a wk | Heparin 5000 U/ml | Bloodstream infection | 0.4 versus 1.37 | 0.02 | Cost |
| Maki et al. (82) | 407 | Multicenter, open-label, randomized, controlled trial | No | Definite catheter-related: fever with concordant positive blood cultures drawn from the catheter and a peripheral vein or a peripheral blood culture and a concordant exit-site culture; concordant catheter-related bloodstream infection: two concordant positive blood cultures but with temperature not exceeding 38.0°C; probable catheter-related bloodstream infection: fever with one positive blood culture | Citrate 7%+methylene blue+methylparabens/propylparaben | Heparin 5000 U/ml | Bloodstream infection | 0.24 versus 0.82 | 0.005 | Not FDA approved |
| Broom et al. (83) | 49 | Multicenter, open-label, randomized, controlled trial | Yes | KDOQI (8) | Ethanol 70% once a wk+heparin 1000 U/ml twice a wk | Heparin 1000 U/ml | Bloodstream infection | 0.28 versus 0.85 | 0.12 | Small proof-of-concept study. potential symptoms, hepatotoxicity and mechanical changes in catheter polymer using high-dose ethanol |
| Sofroniadou et al. (84) | 103 | Single-center, randomized, controlled trial | Yes | CDC/IDSA (11) | Ethanol 70%+heparin 2000 U/ml | Heparin 2000 U/ml | Bloodstream infection | 2.53 versus 6.7 | 0.04 | Short-term study, potential symptoms, hepatotoxicity and mechanical changes in catheter polymer using high-dose ethanol |
| Vercaigne et al. (85) | 40 | Multicenter, randomized, controlled trial | No | Two or more positive blood cultures of the same organism from any source (peripheral or intravascular device cultures) from a patient with no other source of infection | Ethanol 30%+citrate 4% | Heparin 1000 U/ml | Bloodstream infection | 0 versus 0.75 | 0.12 | Small pilot study |
| El-Hennawy et al. (86) | 452 | Single-center, open-label, randomized, controlled trial | Yes | CDC/IDSA (10) | Sodium bicarbonate (7.5% or 8.4%) | Normal saline 0.9% | a) Bloodstream infection b) Catheter loss due to thrombosis c) Catheter loss due to bloodstream infection | a) 0.17 versus 2.6 b) 0.4% versus 0.6% c) 0.4% versus 6.6% | 0.01 <0.001 <0.001 |
N/A, not available; CDC, Centers for Disease Control and Prevention; IDSA, Infectious Disease Society of America; MRSA, methicillin resistant Staphylococcus aureus; NHSN, National Healthcare Safety Network; KDOQI, Kidney Disease Outcomes Quality Initiative; FDA, Food and Drug Administration.