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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave 2014 Ene;15(1):e6069 doi: 10.5867/medwave.2015.01.6069
Does antibiotic lock therapy prevent catheter-associated bacteremia in hemodialysis?
Macarena Jiménez, Trinidad Madrid
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Abstract

Central venous catheter-related blood stream infection is a major cause of morbidity and mortality in patients with renal disease treated with hemodialysis. Antibiotic lock solutions can be effective in preventing this complication in patients with hemodialysis. Searching in Epistemonikos database, which is maintained by screening more than twenty databases, we identified eight systematic reviews including seventeen randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that antibiotic lock solutions probably decrease catheter-related blood stream infection in hemodialysis patients.


 
Problem

Central venous catheter-related blood stream infections can lead to serious infectious complications in patients with renal disease treated with hemodialysis, such as infective endocarditis, septic pulmonary emboli, osteomyelitis and abscesses as a result of hematogenous seeding.

Despite the risks associated to this type of vascular access, many times it is the only option because of temporary loss of permanent hemodialysis access, peripheral vascular disease or as transitory alternative while waiting for the maturation of arteriovenous fistula. Intraluminal antibiotic lock solutions that are maintained for a specified time before being removed can be useful for decreasing the risk of central venous catheter-related blood stream infections.

Methods

We used Epistemonikos database, which is maintained by screening more than 20 databases, to identify systematic reviews and their included primary studies.

With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • Antibiotic lock solutions probably decrease catheter-related blood stream infections in hemodialysis patients.
  • The benefit/risk and benefit/cost balance probably favor the intervention
About the body of evidence for this question

What is the evidence
See evidence matrix in Epistemonikos later.

We found 8 systematic reviews [1],[2],[3],[4],[5],[6],[7],[8]
that include 17 randomized trials [9],[10],[11],[12],[13],
[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25]. 

What types of patients were included

The trials included patients with no distinction by sex or age.

All of the trials included hemodialysis patients, using tunneled (11 trials), non-tunneled (4 trials) or both types of catheters (2 trials).

The randomized trials included 1921 adult patients.

What types of interventions were included

The studies employed different kind of antibiotics as lock therapy (vancomycin, gentamicin, minocicline, cefotaxime, cefazoline and linezolid; associated to heparin, tricitasol, citrate or etildiaminotetraacetic acid).

All trials compared against heparin in the control group.

What types of outcomes were measured

  

Bacteremia/ central venous catheter-related blood stream infection, time until infection, exit-site infection, catheter-associated mortality, total mortality.

 
Summary of findings

This information is based on 17 randomized trials. All of them reported central venous catheter-related blood stream infection.

  •  Antibiotic lock solutions probably decrease catheter-related blood stream infection in hemodialysis patients.

Other considerations for decision-making                                              

To whom this evidence does and does not apply
  •  Trials included patients treated with hemodialysis, with tunneled or non tunneled catheter, so this evidence applies to all these groups.  
  • This evidence does not apply directly to other kind of users of central venous catheter, such as hematologic patients or children. 
 About the outcomes included in this summary
  • Most guidelines consider central venous catheter –related blood stream infection as the critical outcome for decision making. 
  • There is no description of adverse effects in the included trials,  being this an important outcome.

Balance between benefits and risks, and certainty of the evidence
  • There is certainty about the benefits. However, the uncertainty about the adverse effects, such as toxicity or antibiotic resistance, limit the ability to estimate the risk/benefit. 
  • However, it seems likely that the balance is favorable, especially in patients at increased risk of infection
 What do patients and their doctors think about
  • Due to the high incidence of central venous catheter-related blood stream infections in patients treated with hemodialysis, with consequent morbidity and mortality, longer hospital stay  and associated costs, patients and their physicians will be probably inclined to use this option.

Resource considerations 
  • It is difficult to estimate costs given the heterogenity in type and dose of drugs in use.
  • However, it is likely that this balance will be favorable to the intervention.  

Feasibility and implementation
  •  Given the variety of antibiotics and preparations used it is difficult to implement a uniform prevention strategy for different health centers.  Availability and local microbiological data are key to implement the most appropriate option. 

Differences between this summary and other sources
  • The key messages of our summary are consistent with the findings of the individual systematic reviews identified. 
  • The key messages of our summary are discordant with the main clinical practice guideline identified (26) which recommends its use only in patients with multiple central venous catheter-related blood stream infections. The guideline states that  current evidence supports its use, but more trials are lacking with more patients and more homogeneity in the therapy implemented.   

Could this evidence change in the future? 
  • The probability that new trials change the conclusions of this summary is very low, because the certainty of the evidence is high. 
  • New trials comparing different antibiotics could give relevant information for the implementation in specific setting, but the availability and local microbiology might be sufficient to make a decision. 
  • As trials with longer follow up are conducted, we will know if there are adverse effects related to this intervention.


How we conducted this summary
Using automated and collaborative means we compiled all the relevant evidence for the question of interest and we present a matrix of evidence

Matrix of evidence

Follow the link to access the interactive version: Antibiotic lock therapy for prevention of central venous catheter-related blood stream infection in hemodialysis

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary.

Even though the project considers the periodical update of these summaries, users are invited to comment in the website of Medwave or to contact the authors through email if they realize there is new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce this summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organisation aiming to bring information closer to those making health decisions, through the use of technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Follow the link to access the interactive version Antibiotic lock therapy for prevention of central venous catheter-related blood stream infection in hemodialysis

Matrix of evidence
Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Las infecciones del torrente sanguíneo asociadas a catéteres venosos centrales son una de las principales complicaciones de su uso, lo cual conlleva a un aumento de morbimortalidad en pacientes con insuficiencia renal en hemodiálisis. El uso de soluciones de sellado con antibióticos podría ser efectivo para prevenir esta complicación. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en más de veinte bases de datos, identificamos ocho revisiones sistemáticas que en conjunto incluyen diecisiete estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de soluciones de sellado con antibióticos probablemente disminuye el número de infecciones del torrente sanguíneo asociadas a catéteres venosos centrales en pacientes en hemodiálisis.

Authors: Macarena Jiménez[1], Trinidad Madrid[1]

Affiliation:
[1] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: mtmadrid@uc.cl

Author address:
[1] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

Citation: Jiménez M, Madrid T. Does antibiotic lock therapy prevent catheter-associated bacteremia in hemodialysis?. Medwave 2014 Ene;15(1):e6069 doi: 10.5867/medwave.2015.01.6069

Publication date: 22/1/2015

PubMed record

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  1. Jaffer Y, Selby NM, Taal MW, Fluck RJ, McIntyre CW. A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection. Am J Kidney Dis. 2008 Feb;51(2):233-41. | CrossRef | PubMed |
  2. James MT, Conley J, Tonelli M, Manns BJ, MacRae J, Hemmelgarn BR. Meta-analysis: antibiotics for prophylaxis against hemodialysis catheter-related infections. Ann Intern Med. 2008 Apr 15;148(8):596-605. | CrossRef | PubMed |
  3. Labriola L, Crott R, Jadoul M. Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials. Nephrol Dial Transplant. 2008 May;23(5):1666-72. | CrossRef | PubMed |
  4. Rabindranath KS, Bansal T, Adams J, Das R, Shail R, MacLeod AM, et al. Systematic review of antimicrobials for the prevention of haemodialysis catheter-related infections. Nephrol Dial Transplant. 2009 Dec;24(12):3763-74. | CrossRef | PubMed |
  5. Snaterse M1, Rüger W, Scholte Op Reimer WJ, Lucas C. Antibiotic-based catheter lock solutions for prevention of catheter-related bloodstream infection: a systematic review of randomised controlled trials. J Hosp Infect. 2010 May;75(1):1-11. | CrossRef | PubMed |
  6. Wang AY, Ivany JN, Perkovic V, Gallagher MP, Jardine MJ. Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials. Nephrol Dial Transplant. 2013 Nov;28(11):2875-88. | CrossRef | PubMed |
  7. Yahav D, Rozen-Zvi B, Gafter-Gvili A, Leibovici L, Gafter U, Paul M. Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: systematic review and meta-analysis of randomized, controlled trials. Clin Infect Dis. 2008 Jul 1;47(1):83-93. | CrossRef | PubMed |
  8. Zacharioudakis IM, Zervou FN1, Arvanitis M1, Ziakas PD1, Mermel LA1, Mylonakis E1. Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014 Dec 15;59(12):1741-9. | CrossRef | PubMed |
  9. Al-Hwiesh AK, Abdul-Rahman IS. Successful prevention of tunneled, central catheter infection by antibiotic lock therapy using vancomycin and gentamycin. Saudi J Kidney Dis Transpl. 2007 Jun;18(2):239-47. | PubMed |
  10. Bleyer AJ, Mason L, Russell G, Raad II, Sherertz RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocycline-EDTA) in temporary hemodialysis access. Infect Control Hosp Epidemiol. 2005 Jun;26(6):520-4. | PubMed |
  11. Campos RP, do Nascimento MM, Chula DC, Riella MC. Minocycline-EDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol. 2011 Oct;22(10):1939-45. | CrossRef | PubMed |
  12. Cooper RI, Saad TF. Prevention of bacteremia in patients with tunneled cuffed "permanent" hemodialysis catheters (PCs) using gentamicin catheter packing. J Am Soc Nephrol. 1999;10:203A.
  13. Dogra GK, Herson H, Hutchison B, Irish AB, Heath CH, Golledge C, et al. Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: a randomized controlled study. J Am Soc Nephrol. 2002 Aug;13(8):2133-9. | CrossRef | PubMed |
  14. Filiopoulos V, Hadjiyannakos D, Koutis I, Trompouki S, Micha T, Lazarou D, Vlassopoulos D. Approaches to prolong the use of uncuffed hemodialysis catheters: results of a randomized trial. Am J Nephrol. 2011;33(3):260-8. | CrossRef | PubMed |
  15. Kim SH, Song KI, Chang JW, Kim SB, Sung SA, Jo SK, et al. Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: a prospective, randomized clinical trial. Kidney Int. 2006 Jan;69(1):161-4. | CrossRef | PubMed |
  16. McIntyre CW, Hulme LJ, Taal M, Fluck RJ. Locking of tunneled hemodialysis catheters with gentamicin and heparin. Kidney Int. 2004 Aug;66(2):801-5. | CrossRef | PubMed |
  17. Moran J, Sun S, Khababa I, Pedan A, Doss S, Schiller B. A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients. Am J Kidney Dis. 2012 Jan;59(1):102-7. | CrossRef | PubMed |
  18. Nori US, Manoharan A, Yee J, Besarab A. Comparison of low-dose gentamicin with minocycline as catheter lock solutions in the prevention of catheter-related bacteremia. Am J Kidney Dis. 2006 Oct;48(4):596-605. | CrossRef | PubMed |
  19. Pervez A, Ahmed M, Ram S, Torres C, Work J, Zaman F, et al. Antibiotic lock technique for prevention of cuffed tunnel catheter associated bacteremia. J Vasc Access. 2002 Jul-Sep;3(3):108-13. | CrossRef |
  20. Saxena AK, Panhotra BR. The impact of catheter-restricted filling with cefotaxime and heparin on the lifespan of temporary hemodialysis catheters: a case controlled study. J Nephrol. 2005 Nov-Dec;18(6):755-63. | PubMed |
  21. Saxena AK, Panhotra BR, Sundaram DS, Al-Hafiz A, Naguib M, Venkateshappa CK, et al. Tunneled catheters' outcome optimization among diabetics on dialysis through antibiotic-lock placement. Kidney Int. 2006 Nov;70(9):1629-35. | CrossRef | PubMed |
  22. Saxena AK, Panhotra BR, Sundaram DS, Morsy MN, Al-Ghamdi AM. Enhancing the survival of tunneled haemodialysis catheters using an antibiotic lock in the elderly: a randomised, double-blind clinical trial. Nephrology (Carlton). 2006 Aug;11(4):299-305. | CrossRef | PubMed |
  23. Sofroniadou S, Revela I, Smirloglou D, Makriniotou I, Zerbala S, Kouloubinis A, et al. Linezolid versus vancomycin antibiotic lock solution for the prevention of nontunneled catheter-related blood stream infections in hemodialysis patients: a prospective randomized study. Semin Dial. 2012 May;25(3):344-50. | CrossRef | PubMed |
  24. Zhang P, Yuan J, Tan H, Lv R, Chen J. Successful prevention of cuffed hemodialysis catheter-related infection using an antibiotic lock technique by strictly catheter-restricted antibiotic lock solution method. Blood Purif. 2009;27(2):206-11. | CrossRef | PubMed |
  25. Zhang P, Zhang W, Qiang H, Yuan J, Xie W, Jiang H. A randomized controlled study on prevention of cuff-tunneled catheter related bacteremia with gentamicin-heparin lock solution. Renal Week, San Diego; 2006: 592A.
  26. O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011 May;52(9):e162-93. | CrossRef | PubMed |
Jaffer Y, Selby NM, Taal MW, Fluck RJ, McIntyre CW. A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection. Am J Kidney Dis. 2008 Feb;51(2):233-41. | CrossRef | PubMed |

James MT, Conley J, Tonelli M, Manns BJ, MacRae J, Hemmelgarn BR. Meta-analysis: antibiotics for prophylaxis against hemodialysis catheter-related infections. Ann Intern Med. 2008 Apr 15;148(8):596-605. | CrossRef | PubMed |

Labriola L, Crott R, Jadoul M. Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials. Nephrol Dial Transplant. 2008 May;23(5):1666-72. | CrossRef | PubMed |

Rabindranath KS, Bansal T, Adams J, Das R, Shail R, MacLeod AM, et al. Systematic review of antimicrobials for the prevention of haemodialysis catheter-related infections. Nephrol Dial Transplant. 2009 Dec;24(12):3763-74. | CrossRef | PubMed |

Snaterse M1, Rüger W, Scholte Op Reimer WJ, Lucas C. Antibiotic-based catheter lock solutions for prevention of catheter-related bloodstream infection: a systematic review of randomised controlled trials. J Hosp Infect. 2010 May;75(1):1-11. | CrossRef | PubMed |

Wang AY, Ivany JN, Perkovic V, Gallagher MP, Jardine MJ. Anticoagulant therapies for the prevention of intravascular catheters malfunction in patients undergoing haemodialysis: systematic review and meta-analysis of randomized, controlled trials. Nephrol Dial Transplant. 2013 Nov;28(11):2875-88. | CrossRef | PubMed |

Yahav D, Rozen-Zvi B, Gafter-Gvili A, Leibovici L, Gafter U, Paul M. Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: systematic review and meta-analysis of randomized, controlled trials. Clin Infect Dis. 2008 Jul 1;47(1):83-93. | CrossRef | PubMed |

Zacharioudakis IM, Zervou FN1, Arvanitis M1, Ziakas PD1, Mermel LA1, Mylonakis E1. Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014 Dec 15;59(12):1741-9. | CrossRef | PubMed |

Al-Hwiesh AK, Abdul-Rahman IS. Successful prevention of tunneled, central catheter infection by antibiotic lock therapy using vancomycin and gentamycin. Saudi J Kidney Dis Transpl. 2007 Jun;18(2):239-47. | PubMed |

Bleyer AJ, Mason L, Russell G, Raad II, Sherertz RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocycline-EDTA) in temporary hemodialysis access. Infect Control Hosp Epidemiol. 2005 Jun;26(6):520-4. | PubMed |

Campos RP, do Nascimento MM, Chula DC, Riella MC. Minocycline-EDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol. 2011 Oct;22(10):1939-45. | CrossRef | PubMed |

Cooper RI, Saad TF. Prevention of bacteremia in patients with tunneled cuffed "permanent" hemodialysis catheters (PCs) using gentamicin catheter packing. J Am Soc Nephrol. 1999;10:203A.

Dogra GK, Herson H, Hutchison B, Irish AB, Heath CH, Golledge C, et al. Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: a randomized controlled study. J Am Soc Nephrol. 2002 Aug;13(8):2133-9. | CrossRef | PubMed |

Filiopoulos V, Hadjiyannakos D, Koutis I, Trompouki S, Micha T, Lazarou D, Vlassopoulos D. Approaches to prolong the use of uncuffed hemodialysis catheters: results of a randomized trial. Am J Nephrol. 2011;33(3):260-8. | CrossRef | PubMed |

Kim SH, Song KI, Chang JW, Kim SB, Sung SA, Jo SK, et al. Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: a prospective, randomized clinical trial. Kidney Int. 2006 Jan;69(1):161-4. | CrossRef | PubMed |

McIntyre CW, Hulme LJ, Taal M, Fluck RJ. Locking of tunneled hemodialysis catheters with gentamicin and heparin. Kidney Int. 2004 Aug;66(2):801-5. | CrossRef | PubMed |

Moran J, Sun S, Khababa I, Pedan A, Doss S, Schiller B. A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients. Am J Kidney Dis. 2012 Jan;59(1):102-7. | CrossRef | PubMed |

Nori US, Manoharan A, Yee J, Besarab A. Comparison of low-dose gentamicin with minocycline as catheter lock solutions in the prevention of catheter-related bacteremia. Am J Kidney Dis. 2006 Oct;48(4):596-605. | CrossRef | PubMed |

Pervez A, Ahmed M, Ram S, Torres C, Work J, Zaman F, et al. Antibiotic lock technique for prevention of cuffed tunnel catheter associated bacteremia. J Vasc Access. 2002 Jul-Sep;3(3):108-13. | CrossRef |

Saxena AK, Panhotra BR. The impact of catheter-restricted filling with cefotaxime and heparin on the lifespan of temporary hemodialysis catheters: a case controlled study. J Nephrol. 2005 Nov-Dec;18(6):755-63. | PubMed |

Saxena AK, Panhotra BR, Sundaram DS, Al-Hafiz A, Naguib M, Venkateshappa CK, et al. Tunneled catheters' outcome optimization among diabetics on dialysis through antibiotic-lock placement. Kidney Int. 2006 Nov;70(9):1629-35. | CrossRef | PubMed |

Saxena AK, Panhotra BR, Sundaram DS, Morsy MN, Al-Ghamdi AM. Enhancing the survival of tunneled haemodialysis catheters using an antibiotic lock in the elderly: a randomised, double-blind clinical trial. Nephrology (Carlton). 2006 Aug;11(4):299-305. | CrossRef | PubMed |

Sofroniadou S, Revela I, Smirloglou D, Makriniotou I, Zerbala S, Kouloubinis A, et al. Linezolid versus vancomycin antibiotic lock solution for the prevention of nontunneled catheter-related blood stream infections in hemodialysis patients: a prospective randomized study. Semin Dial. 2012 May;25(3):344-50. | CrossRef | PubMed |

Zhang P, Yuan J, Tan H, Lv R, Chen J. Successful prevention of cuffed hemodialysis catheter-related infection using an antibiotic lock technique by strictly catheter-restricted antibiotic lock solution method. Blood Purif. 2009;27(2):206-11. | CrossRef | PubMed |

Zhang P, Zhang W, Qiang H, Yuan J, Xie W, Jiang H. A randomized controlled study on prevention of cuff-tunneled catheter related bacteremia with gentamicin-heparin lock solution. Renal Week, San Diego; 2006: 592A.

O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis. 2011 May;52(9):e162-93. | CrossRef | PubMed |

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