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Maki, 1991
Nimoz, 1996
Humar, 2000
Langgartner.2004
Chaiyakunapruk, 2002

 

Efficacy of Chlorhexidine-Containing Cutaneous Antiseptics in Prevention of (Vascular) Catheter Related Infection. 

Andrew Longmate on behalf of the SICS EBM group 

Intensive Care Unit, Stirling Royal Infirmary, Livilands,  Stirling FK8 2AU

Correspondence: Andrew.Longmate@fvah.scot.nhs.uk

Citation: EBM Reviews. Scottish Intensive Care Society EBM Group. Andrew Longmate. Efficacy of Chlorhexidine-Containing Cutaneous Antiseptics in Prevention of (Vascular) Catheter Related Infection. 2005

Background: (Vascular) Catheter related bloodstream infection is associated with an increased morbidity, mortality, length of hospitalization and medical costs. The pathophysiology of catheter related infection  remains uncertain but three main possibilities have been identified. These include skin colonisation and invasion of the transcutaneous insertion tract by micro-organisms of the patient ‘s own flora, hub colonisation with contiguous intraluminal spread or infusate contamination. Heavy cutaneous colonisation is a risk factor for CVC related BSI and chlorhexidine is a potent germicide that has been used for many years for skin disinfection. Multimodal strategies are important in the prevention of intensive care associated infections including catheter related blood stream infections. However Chlorhexidine containing cutaneous antiseptics have been widely recommended for use prior to catheter insertion to prevent CrBSI. 

Objectives: The objectives of this search was to assess published RCTs and meta-analyses that have attempted to address whether the use of chlorhexidine skin preparation may be beneficial in preventing catheter related bloodstream infection.

Search strategy: Medline(1) catheterisation (explode) (2) catheterisation/ or catheterization, Swan-Ganz/ or Heart Catheterization/ or ctaheterisation.mp or Catheterization, Central venous (3) 1 and 2 (4)infection or infection m.p. (5) 3 and 4 (6) limit 5 to English language and "all adult(19 plus years)" and meta analysis. (7) limit 5 to "all adult(19 plus years)" and randomised controlled trial (8) 6 or 7. This resulted in 21 publications. Additional hand searches of reference lists from these publications and review articles. 

Selection criteria: RCTs or meta-analysis published in peer reviewed journals comparing rates of catheter colonization or infection between different antiseptic skin regimes prior to insertion of vascular catheter (arterial or central venous catheter).

Excluded tunnelled catheters, antimicrobial impregnated catheters, non adult patients and non ITU patients, insertion site infections and articles not published in English language. Studies presented at meetings or in abstract form were also excluded. 

Definitions: Definitions used vary between different studies which  can make comparisons confusing. For the purposes of this review the results have been limited to 2 main groups: catheter colonization and bacteraemic catheter related blood stream infection.  

  1. Colonisation:  is clearly a surrogate marker which fits with one potential mechanism of infection which assumes that catheter colonisation is a key step to catheter related blood stream infection. It may not have direct clinical implications. The 3  main ways to define colonisation include

•      Qualitative: isolation of organism from catheter tip.

•      Semiquantative: Greater or equal to 15 colony forming units (by roll plate technique)

•      Quantitative estimation: greater than 10 3 bacteria

  1. Bacteraemic Catheter Related Blood Stream Infection: can be defined as bacteraemia (or fungaemia) in a patient with an intravascular catheter with at least one positive blood culture obtained from a peripheral vein , clinical manifestations of infection (ie fever, chills and/or hypotension) and no apparent source of BSI except the catheter. One of the following should be present: a positive semiquantitative (>15cfu/catheter segment) or quantitative (>103 cfu/catheter segment cartheter) culture whereby the same organism  (species and antibiogram) is isolated from the catheter segment and the peripheral blood.  (from CDC definition)

Search results: Produce 5 papers – Four  RCTs1-4, one meta-analysis5.

Analysis of the Evidence:

  1. Colonisation (Data was analysed by CATmakerTM software)

  • 2 Trials showed a significant reduction in colonisation using chlorhexidine compared to povidone iodine(1,2).
  • 2 Trials showed no significant difference (3,4). One study was not adequately powered to detect a difference(3) and the other (4) showed a trend towards reduction.
  • 1 Trial Showed that combination iodine/chlorhexidine better than either alone for prevention of colonisation (4).

 

Central Venous Catheters

First Author of Trial (refernce):

Maki (1)

Mimoz (2)

Humar (3)

Langgartner (4)

Colonisation definition

> 15cfus

>/=103 cfus/ml

> 15cfus

> 15cfus

 

 

Control

Group

 

 

Control Agent(s)

10% povidone iodine or 70% alcohol

10% povidone iodine

10% povidone iodine

10%                    povidone  iodine

% incidence

18.3%

 

27%

30.8%

(numbers)

20/109

 

24/88

16/52

per 1000 pat days

 

31

46

21

 

Chlorhexidine

Formulation

2% aqueous

0.25%

4% alcohol

0.5% tincture

0.5%

70% alcohol

% incidence

5.9%

 

34%

24.4%

(numbers)

4/67

 

31/92

11/45

per 1000 pat days

 

8

34

18.8

Sequential

% incidence

 

 

 

4.7%

 

(numbers)

 

 

 

2/43

 

per 1000 pat days

not tested

not tested

not tested

3.5

Chlorhex. v. Iodine

RR(95% CI)

Relative Risk

0.33

(0.26-0.39)

reduction

 

1.24

(1.16-1.31)

N/S

0.79                         (0.71-0.87)

*

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

* Apparently shows significant reduction.  Not verified by authors.

 

Central Venous Catheters  and Arterial Catheters

First Author of Trial:

Maki

Mimoz

Humar

Langgartner

Colonisation definitions

> 15cfus

>/=103 cfus per ml

 

 

 

 

Control

Group

 

 

Control Agent(s)

10% povidone iodine or 70% alcohol

10% povidone iodine

 

 

% incidence

7%

17%

 

 

(numbers)

32/454

24/145

 

 

per 1000 pat days

not given

31

 

 

 

Chlor hex.

Formulation

2% aqueous

0.25%

4% alcohol

 

 

% incidence

2.3%

7.1%

 

 

(numbers)

5/214

12/170

 

 

per 1000 pat days

not given

12

 

 

Sequential

% incidence

 

 

 

 

 

(numbers)

 

 

 

 

 

per 1000 pat days

not tested

not tested

 

 

Chlor hex. v. Iodine

RR(95% CI)

Relative Risk

0.33

(0.3-0.37)

reduction

0.43 check

(0.37-0.48)

reduction

 

 

 

  1. Catheter Related Bacteraemic Blood Stream Infection (BSI)

  • The definition used for purposes of this review includes isolation of the same organism from the catheter tip and peripheral blood culture.

  • One trial showed a benefit for one definition of catheter related blood stream infection. (2). However their definition was non standard and did not require positive blood culture of the same organism from a peripheral vein as was isolated from the catheter tip segment. They were unable to show any difference for bacteraemic CrBSI. One trial did not look at bacteraemic infection as an end point. (4)

  • The other 2 studies failed to show a statistically significant difference in catheter related bloodstream infection. (bacteraemic catheter related blood stream infection).

 

CVCs and a lines

First Author of Trial:

Maki

Mimoz

Humar

Catheter Realated Bacteraemia

 

 

 

 

 

Control

Group

 

 

Control Agent(s)

10% povidone iodine or 70% alcohol

10% povidone iodine

 

% incidence

1.98

 

 

(numbers)

9/54

 

 

per 1000 pat days

 

4

 

 

Chlor hexidine

Formulation

 

 

 

% incidence

0.46

 

 

(numbers)

1/214

 

 

per 1000 pat days

 

 

 

Sequential

% incidence

 

 

 

 

(numbers)

 

 

 

 

per 1000 pat days

 

3

 

Chlor hexidine v. Iodine

RR(95% CI)

Relative Risk

N/S

RR 0.7

95%CI 0.1-2.2 p=0.4

N/S

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  

CVCs Only

First Author of Trial (refernce):

Maki (1)

Mimoz (2)

Humar (3)

Catheter Related Bacteraemia

 

 

 

 

 

Control

Group

 

 

Control Agent(s)

10% povidone iodine or 70% alcohol

10% povidone iodine

10% povidone iodine

% incidence

6.4

 

3.4

(numbers)

7/109

 

4/117

per 1000 pat days

 

 

4.1

 

Chlor hexidine

Formulation

2% aqueous

0.25%

4% alcohol

0.5% tincture

% incidence

1.4

 

3.2

(numbers)

1/67

 

4/125

per 1000 pat days

 

 

4.6

Sequential

% incidence

 

 

 

 

(numbers)

 

 

 

 

per 1000 pat days

not tested

not tested

not tested

Chlor hexidine v. Iodine

RR(95% CI)

Relative Risk

 

 

N/S
 
 
 
 
 
 

 

 

 

 

 

 

 

 

 Meta analysis:

One meta analysis was reviewed (5). The Meta analysis used the 4 studies noted above and an additional  5 other studies which are listed below and have not been assessed separately in this review. The meta-analysis included non ITU patients and all vascular catheters including peripheral venous lines.

There was significant reduction in colonisation rates associated with use of chlorhexidine but authors correctly stated that the study populations were too heterogenous to allow their results to be collated.

When applied to Catheter related bloodstream infections the study populations were homogenous enough to allow collation. They found that use of chlorhexidine gluconate can reduce the risk for catheter related bloodstream infection by approximately 50%.

 

Reviewers conclusions: 

 

·       In ITU adult patients there is some evidence to support the preferential use of chlorhexidine over povidone iodine for skin antisepsis before catheter insertion to prevent catheter colonisation. Certainly chlorhexidine is no worse than povidone iodine. One trial has shown a benefit when using the combination of sequential chlorhexidine and povidone iodine4 over either agent alone.

 

·       Different studies use different formulations (aqueous or alcoholic) and concentrations (0.5% to 2%). of chlorhexidine Different formulations of iodine and or alcohol were used as control groups. 

 

·        A chlorhexidine containing solution should be considered for use as skin asepsis prior to vascular catheter insertion (arterial catheter or CVC) with the aim of reducing catheter colonization.

 

·        Consideration should be made to using sequential chlorhexidine and povidone iodine skin preparation to prevent catheter colonization.

 Areas of further research:  Further trials using combined sequential antisepsis would be useful to examine the effects on colonisation. Further trails assessing effects on catheter related bloodstream infection would be difficult because of the number of potential confounding variables and would require large numbers of patients.

 Citations with links to CATs: 

  1. Maki DG, et al. Prospective Randomised Trial of Povidone-Iodine, Alcohol, and Chlorhexidine for Prevention of Infection Associated with Central Venous and Arterial Catheters. Lancet, 1991: 338; 339-343.CAT.

  2. Mimoz O, et al. Prospective , randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients. Critical Care Medicine, 1996;24 18818-23. CAT.

  3. Humar A, et al. Prospective Randomised Trial of 10% Povidone-Iodine versus 0.5% Tincture of Chlorhexidine as Cutaneous Antisepsis for Prevention of Central Venous Catheter Infection. Clinical Infectious Disease 2000; 31: 1001-7. CAT.

  4.  Langgartner J, et al. Combined skin disinfection with chlorhexidine/propanol and aqueous povidone iodine reduces bacterial colonization of central venous catheters. Intensive Care Medicine (2004) 30: 1081-1088. CAT.

  5. Chaiyakunapruk N, et al. Chlorhexidine Campared with Povidone-Iodine Solution for Vascular Catheter-Site Care: A Meta-Analysis. Ann Intern Med. 2002;136:792-801. CAT.

The meta analysis reviewed the papers above (1-4) and the 5 studies below.

•Sheehan et al Chlorhexidine versus povidone iodine as cutaneous antisepsis for prevention of vascular catheter infections. Abstract 1993 Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology

•Meffre et al Is peripheral venous catheter colonisation related to the antiseptic used for disinfection of the insertion site ? Povidone iodine vs alcoholic chlkorhexidine: a multicentre randomised prospective study. Abstract 1995. Catheter Study Group. Hygienes

•Legras et al. Etude prospectitive randomisee pour la prevntion des infections liees aux catheters: chlorhexidine alcoolique contre povidone iodee. 1997 Reanimation et Urgences

•LeBlanc and Cobett. IV site infection: a prospective randomised clinical trial comparing the efficacy of three methods of asepsis. 1999 Canadian Intravenous Nurses Association Journal.

•Knasinski and Maki. A prospective randomised controlled trial of 1% chlorhexidine 75% alcohol vs 10% povidone iodine for cutaneous disinfection and follow up site care with central venous and arterial catheters. 2000. Presented paper. National Association of Vascular Access Network Conference.

 Reviewed & Edited DS, CC, BC, MD

 

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