Skip Navigation U.S. Department of Health and Human Services www.hhs.gov
Agency for Healthcare Research Quality www.ahrq.gov
Archive print banner

This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: https://info.ahrq.gov. Let us know the nature of the problem, the Web address of what you want, and your contact information.

Please go to www.ahrq.gov for current information.

Chapter 16. Prevention of Intravascular Catheter-Associated Infections (continued)

Subchapter 16.3. Use of Chlorhexidine Gluconate at the Central Venous Catheter Insertion Site

Practice Description

Microbial populations on the skin are routinely suppressed with antiseptic agents prior to catheter insertion. Using an antiseptic solution for skin disinfection at the catheter insertion site helps to prevent catheter-related infections. The physician uses an agent that has antimicrobial properties to thoroughly cleanse the skin just prior to insertion of a central venous catheter. In the United States, povidone-iodine (PI) is overwhelmingly the most commonly used agent for this purpose. Recently, several studies have compared the efficacy of PI and chlorhexidine gluconate (CHG) solutions in reducing vascular catheter-related infections.

Opportunities for Impact

If PI is the most commonly used agent for site disinfection in the United States even though CHG may be superior, substantial opportunity exists for impact by switching to CHG.

Study Designs

The study characteristics of 6 randomized trials48-53 comparing any type of CHG solution with PI solution for vascular catheter site care are shown in Table 16.3.1. The mean duration of catheterization for the CHG and PI groups was comparable in most of the studies. There was no significant difference in the sites at which catheters were inserted between the CHG and PI groups. Several formulations of CHG were used, including9,12-14 an alcoholic solution and an aqueous solution. All studies used 10% PI solution for the control arm.

Study Outcomes

All studies48-53 evaluated catheter colonization (Level 2 outcome) and all but one52 evaluated CR-BSI (Level 1 outcome). All studies evaluating CR-BSI as an outcome required the recovery of the same microbial species from both the catheter segment and a blood culture.

Evidence for Effectiveness of the Practice

Most clinical trials have revealed that the use of CHG solution results in a significant decrease in catheter colonization, but the evidence is not clear for CR-BSI (Table 16.3.2). Most of the individual trials showed a trend in reducing CR-BSI incidence in patients using CHG solution. The lack of significant results may be a result of insufficient statistical power in the individual studies. A formal meta-analysis of the published trials would be valuable in assessing the comparative efficacy of PI versus CHG for central venous catheter site disinfection. Using explicit inclusion criteria and accepted quantitative methods, a meta-analysis54-56 can often help clarify the features of individual studies that have divergent results and increase statistical power since several small studies can be pooled.58

Potential for Harm

Only one study reported adverse effects from the use of either antiseptic solution. Maki et al48 found erythema at the insertion site in 28.3% of catheters in the PI group and in 45.3% of catheters in the CHG group (p=0.0002). However, there was no statistically significant difference in erythema among these 2 groups and those patients whose site was disinfected with alcohol. Hypersensitivity reactions to chlorhexidine-silver sulfadiazine impregnated central venous catheters and to use of CHG for bathing have been reported. Hypersenstivity reactions were not reported in any of the studies, but clinicians should be aware of such potential side effects. Another concern is the development of bacterial resistance. However, there have been few reports of bacterial resistance to CHG despite its widespread use for several decades.

Costs and Implementation

The cost of CHG is approximately twice that of PI with an absolute difference of $0.51 (approximately $0.92 versus $0.41 for a quantity sufficient to prepare a central venous catheter insertion site). If meta-analysis suggests that CHG use is effective in reducing the risk of CR-BSI, a formal economic evaluation of this issue is required.

Comment

The use of chlorhexidine gluconate rather than povidone-iodine solution for catheter site care may be an effective and simple measure for improving patient safety by reducing vascular catheter-related infections. Formal meta-analysis and economic evaluations are required before strongly recommending that CHG replace PI for central venous catheter site disinfection in appropriate patient populations.

Table 16.3.1. Characteristics of studies comparing chlorhexidine gluconate (CHG) and povidone-iodine (PI) solutions for vascular catheter site care*

Study Descriptiona Number of Catheters (Treatment, Control) Mean Catheter Duration in Days (Treatment, Control) Catheter Colonizationb Catheter-Related Bloodstream Infectionb
Maki48: 441 ICU patients (2% aqueous CHG solution in 214, PI in 227) 214, 227 5.3, 5.3 SQ (>15 CFU) CX, NoSource, Sx
Sheehan49: 189 ICU patients (2% aqueous CHG solution in 94, PI in 95) 169,177 NA SQ (>15 CFU) CX, NoSource, Sx
Meffre50: 1117 hospital patients (CHG solution of 0.5% alcohol 70% in 568, PI in 549) 568, 549 1.6, 1.6 SQ (>15 CFU) or QN (>103 CFU/mL) [Local or Sx] or [CX, NoSource]
Mimoz51: ICU patients (Biseptine® c vs. PI) 170, 145 4.5, 3.9 QN (>103 XFU/mL) CX, Sx
Cobett and LeBlanc52: 244 hospital patients (0.5% alcohol 70% in 8, PI in 161) 83, 161 1.6, 1.7 SQ (>15 CFU)d NA
Humar et al53: 3374 ICU patients (0.5% alcohol in 193 and 181/193 193, 181 5.3, 6. SQ (>15 CFU) CX, Molec, NoSource

* CFU indicates colony forming units; CX, same organism or species matched between blood and catheter segment culture; ICU: intensive care units; Local: local signs of infection; Molec: same organism confirmed by molecular subtyping; NA:not available; NoSource: no other source of infection; QN: quantitative; Sx: clinical symptoms of bloodstream infection; SQ: semiquantitative.

a All studies used 10% povidone-iodine solution.

b Catheter segments (or site) cultured and criteria for a positive culture are given in parenthesis.

c Biseptine® consists of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, 4% benzyl alcohol.

d Required one of the following symptoms: fever, erythema, heat at the site, and pain.

Table 16.3.2. Results of Studies Comparing Chlorhexidine Gluconate (CHG) and Povidone-iodine (PI) Solutions for Vascular Catheter Site Care*

Study Catheter Colonization (Positive Cultures) RR (95% CI)
CHG vs. PI
Catheter Related Bloodstream Infection RR (95% CI)
CHG vs. PI
CHG Solution PI Solution CHG Solution PI Solution
Maki48 5/214 21/227 0.25 (0.10,0.66) 1/214 6/227 0.18 (0.02,1.46)
Sheehan9 3/169 12/177 0.22 (0.06,0.75) 1/169 1/177 1.05 (0.07,16.61)
Meffre50 9/568 22/549 0.40 (0.18,0.85) 3/568 3/549 0.97 (0.20,4.77)
Mimoz51 12/170 24/145 0.43 (0.22,0.82) 3/170 4/145 0.64 (0.15,2.81)
Cobett and LeBlanc52a 6/83 23/161 0.49 (0.31,0.77) - - -
Humar53 36/116 27/116 1.33 (0.87,2.04) 4/193 5/181 0.75 (0.20,2.75)

* CI indicates confidence interval; RR, relative risk.

a Additional information was provided by authors.

Return to Contents

Subchapter 16.4. Other Practices

Practices That Appear Promising

Use of heparin with central venous catheters. Because an association has been shown between thrombus formation and catheter-related infection, clinicians usually use heparin, in a variety of forms: 1) as flushes to fill the catheter lumens between use; 2) injected subcutaneously; or 3) bonded on the catheter. A meta-analysis of 12 randomized trials evaluating prophylactic use of heparin in patients using central venous catheters has shown that prophylactic heparin decreases catheter-related venous thrombosis (Level 2 outcome; RR 0.43, 95% CI: 0.23-078) and bacterial colonization (Level 2 outcome; RR 0.18, 95% CI: 0.06-0.60) and may decrease CR-BSI (Level 1 outcome; RR 0.26, 95% CI: 0.07-1.03).59 Since subcutaneous heparin also offers benefit in reducing venous thromboembolism in certain patient populations (see Chapter 31), this is likely to be a reasonable strategy even though CR-BSIs have not definitely been shown to be reduced. However use of heparin is associated with several side effects, such as heparin-induced thrombocytopenia and bleeding.

Tunneling short-term central venous catheters. Since the primary site of entry for microorganisms on the central venous catheter is the site of cutaneous insertion,60 tunneling the catheter through the subcutaneous tissue may decease the incidence of infection. Several trials have evaluated the effect of tunneling on catheter-related infection. A recent meta-analysis has summarized the potential benefit.61 The meta-analysis included 7 trials and found that compared with patients receiving standard catheter placement, tunneling decreased bacterial colonization (Level 2 outcome; RR 0.61, 95% CI: 0.39-0.95) and decreased CR-BSI (Level 1 outcome; RR 0.56, 95% CI: 0.31-1).61 However, the benefit of tunneling came primarily from one trial using the internal jugular as the site of catheter placement; the reduction in CR-BSI no longer reached statistical significance when data from the several subclavian catheter trials were pooled (RR 0.71; 95% CI 0.36-1.43).61 The authors concluded appropriately that current evidence does not support the routine use of tunneling central venous catheters. This could change if the efficacy of tunneling is clearly demonstrated at different placement sites and relative to other interventions (e.g., antiseptic coated catheters).61

Ineffective Practices

Intravenous antimicrobial prophylaxis. There is no evidence to support the systemic use of either vancomycin62 or teicoplanin63 during insertion of central venous catheters. The randomized studies evaluating the use on intravenous vancomycin or teicoplanin have failed to demonstrate that this intervention reduces CR-BSI (Level 1 outcome).62,63 Given the theoretical risk of developing resistance to the antimicrobial agents used for prophylaxis, this practice is not recommended.

References

1. Raad II, Bodey GP. Infectious complications of indwelling vascular catheters. Clin Infect Dis 1992;15:197-208.

2. Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997;24:584-602.

3. Maki DG. Infections caused by intravascular devices used for infusion therapy. In: Bistro AI, F.A. W, eds. Infections Associated with Indwelling Medical Devices. Washington, DC: ASM Press, 1994:155-205.

4. Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med 2000; 132:391-402.

5. Guideline for prevention of intravascular device-related infections. Am J Infect Control 1996; 24:261-293.

6. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med 1977;296:1305-1309.

7. Sherertz RJ, Heard SO, Raad, II. Diagnosis of triple-lumen catheter infection: comparison of roll plate, sonication, and flushing methodologies. J Clin Microbiol 1997;35:641-646.

8. Flynn PM, Shenep JL, Barrett FF. Differential quantitation with a commercial blood culture tube for diagnosis of catheter-related infection. J Clin Microbiol 1988;26:1045-1046.

9. Blot F, Nitenberg G, Chachaty E, et al. Diagnosis of catheter-related bacteremia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 1999;354:1071-1077.

10. Bozzetti F, Terno G, Camerini E, Baticci F, Scarpa D, Pupa A. Pathogenesis and predictability of central venous catheter sepsis. Surgery 1982;91:383-389.

11. Hampton AA, Sherertz RJ. Vascular-access infections in hospitalized patients. Surg Clin North Am 1988;68:57-71.

12. Corona ML, Peters SG, Narr BJ, Thompson RL. Infections related to central venous catheters. Mayo Clin Proc 1990;65:979-986.

13. Snydman DR, Gorbea HF, Pober BR, Majka JA, Murray SA, Perry LK. Predictive value of surveillance skin cultures in total-parenteral-nutrition-related infection. Lancet 1982;2:1385-1388.

14. Sitges Serra A, Puig P, Linares J, et al. Hub colonization as the initial step in an outbreak of catheter-related sepsis due to coagulase negative staphylococci during parenteral nutrition. JPEN J Parenter Enteral Nutr 1984;8:668-672.

15. Kovacevich DS, Faubion WC, Bender JM, Schaberg DR, Wesley JR. Association of parenteral nutrition catheter sepsis with urinary tract infections. JPEN J Parenter Enteral Nutr 1986;10:639-641.

16. Maki DG, Rhame FS, Mackel DC, Bennett JV. Nationwide epidemic of septicemia caused by contaminated intravenous products. I. Epidemiologic and clinical features. Am J Med 1976;60:471-485.

17. Saint S, Veentra DL, Lipsky BA. The clinical and economic consequences of nosocomial central venous catheter-related infection: are antimicrobial catheters useful? Infect Control Hosp Epidemiol 2000;21:375-380.

18. Anonymous. National Nosocomial Infections Surveillance (NNIS) System report, data summary from October 1986-April 1998, issued June 1998. Am J Infect Control 1998;26:522-533.

19. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1994;271:1598-601.

20. Pittet D, Wenzel RP. Nosocomial bloodstream infections in the critically ill [letter]. JAMA 1994;272:1819-1820.

21. Smith RL, Meixler SM, Simberkoff MS. Excess mortality in critically ill patients with nosocomial bloodstream infections. Chest 1991;100:164-167.

22. Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med 1999;160:976-981.

23. Soufir L, Timsit JF, Mahe C, Carlet J, Regnier B, Chevret S. Attributable morbidity and mortality of catheter-related septicemia in critically ill patients: a matched, risk-adjusted, cohort study. Infect Control Hosp Epidemiol 1999;20:396-401.

24. Cook D, Randolph A, Kernerman P, et al. Central venous catheter replacement strategies: a systematic review of the literature. Crit Care Med 1997;25:1417-1424.

25. Eyer S, Brummitt C, Crossley K, Siegel R, Cerra F. Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. Crit Care Med 1990;18:1073-1079.

26. Cobb DK, High KP, Sawyer RG, et al. A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters . N Engl J Med 1992;327:1062-8.

27. Nystrom B. Impact of handwashing on mortality in intensive care: examination of the evidence. Infect Control Hosp Epidemiol 1994;15:435-436.

28. Doebbeling BN, Stanley GL, Sheetz CT, et al. Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med 1992;327:88-93.

29. Raad, II, Hohn DC, Gilbreath BJ, et al. Prevention of central venous catheter-related infections by using maximal sterile barrier precautions during insertion. Infect Control Hosp Epidemiol 1994;15:231-238.

30. Sherertz RJ, Ely EW, Westbrook DM, et al. Education of physicians-in-training can decrease the risk for vascular catheter infection. Ann Intern Med 2000;132:641-648.

31. Tennenberg S, Lieser M, McCurdy B, et al. A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections. Arch Surg 1997;132:1348-1351.

32. Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med 1997;127:257-266.

33. van Heerden PV, Webb SA, Fong S, Golledge CL, Roberts BL, Thompson WR. Central venous catheters revisited-infection rates and an assessment of the new Fibrin Analysing System brush. Anaesth Intensive Care 1996;24:330-333.

34. Hannan M, Juste R, Shankar U, Nightingale C, Azadian B, Soni N. Colonization of triple lumen catheters. A study on antiseptic-bonded and standard catheters [abstract]. Clin Intensive Care 1996;7:56.

35. Bach A, Bohrer H, Bottiger BW, Motsch J, Martin E. Reduction of bacterial colonization of triple-lumen catheters with antiseptic bonding in septic patients [abstract]. Anesthesiology 1994;81:A261.

36. Bach A, Schmidt H, Bottiger B, et al. Retention of antibacterial activity and bacterial colonization of antiseptic-bonded central venous catheters. J Antimicrob Chemother 1996;37:315-322.

37. Heard SO, Wagle M, Vijayakumar E, et al. Influence of triple-lumen central venous catheters coated with chlorhexidine and silver sulfadiazine on the incidence of catheter-related bacteremia. Arch Intern Med 1998;158:81-87.

38. Collin GR. Decreasing catheter colonization through the use of an antiseptic-impregnated catheter: a continuous quality improvement project. Chest 1999;115:1632-1640.

39. Ciresi DL, Albrecht RM, Volkers PA, Scholten DJ. Failure of antiseptic bonding to prevent central venous catheter-related infection and sepsis. Am Surg 1996;62:641-646.

40. Pemberton LB, Ross V, Cuddy P, Kremer H, Fessler T, McGurk E. No difference in catheter sepsis between standard and antiseptic central venous catheters. A prospective randomized trial. Arch Surg 1996;131:986-989.

41. Ramsay J, Nolte F, Schwarmann S. Incidence of catheter colonization and catheter-related infection with an antiseptic-impregnated triple lumen catheter [abstract]. Crit Care Med 1994;22:A115.

42. Trazzera S, Stern G, Rakesh B, Sinha S, Reiser P. Examination of antimicrobial-coated central venous catheters in patients at high risk for catheter-related infections in a medical intensive care unit and leukemia/bone marrow transplant unit [abstract]. Crit Care Med 1995;23:A152.

43. George SJ, Vuddamalay P, Boscoe MJ. Antiseptic-impregnated central venous catheters reduce the incidence of bacterial colonization and associated infection in immunocompromised transplant patients. Eur J Anaesthesiol 1997;14:428-431.

44. Veenstra DL, Saint S, Saha S, Lumley T, Sullivan SD. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis. JAMA 1999;281:261-267.

45. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group. Ann Intern Med 1997;127:267-274.

46. Darouiche RO, Raad, II, Heard SO, et al. A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl J Med 1999;340:1-8.

47. Veenstra DL, Saint S, Sullivan SD. Cost-effectiveness of antiseptic-impregnated central venous catheters for the prevention of catheter-related bloodstream infection. JAMA 1999;282:554-560.

48. Maki DG, Ringer M, Alvarado CJ. 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.

49. Sheehan G, Leicht K, O'Brien M, Taylor G, Rennie R. Chlorhexidine versus povidone-iodine as cutaneous antisepsis for prevention of vascular-catheter infection [abstract]. Program and abstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy 1993;33:A1616.

50. Meffre C, Girard R, Hajjar J, Fabry J. Is peripheral venous catheter colonisation related to antiseptic used for disinfection of the insertion site? Hygiene 1995;9:45.

51. Mimoz O, Pieroni L, Lawrence C, 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. Crit Care Med 1996;24:1818-1823.

52. Cobett S, LeBlanc A. IV site infection: a prospective, randomized clinical trial comparing the efficacy of three methods of skin antisepsis: CINA conference '99. CINA: Official Journal of the Canadian Intravenous Nurses Association 1999;15:48-49.

53. Humar A, Ostromecki A, Direnfeld J, et al. Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection. Clin Infect Dis 2000;31:1001-1007.

54. Yusuf S. Obtaining medically meaningful answers from an overview of randomized clinical trials. Stat Med 1987;6:281-294.

55. Light RJ. Accumulating evidence from independent studies: what we can win and what we can lose. Stat Med 1987;6:221-231.

56. Hennekens CH, Buring JE, Hebert PR. Implications of overviews of randomized trials. Stat Med 1987;6:397-409.

57. Sacks HS, Berrier J, Reitman D, Ancona Berk VA, Chalmers TC. Meta-analyses of randomized controlled trials. N Engl J Med 1987;316:450-455.

58. Gelber RD, Goldhirsch A. Interpretation of results from subset analyses within overviews of randomized clinical trials. Stat Med 1987;6:371-388.

59. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials. Chest 1998;113:165-171.

60. Mermel LA, McCormick RD, Springman SR, Maki DG. The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a prospective study utilizing molecular subtyping. Am J Med 1991;91:197S-205S.

61. Randolph AG, Cook DJ, Gonzales CA, Brun-Buisson C. Tunneling short-term central venous catheters to prevent catheter-related infection: a meta-analysis of randomized, controlled trials. Crit Care Med 1998;26:1452-1457.

62. McKee R, Dunsmuir R, Whitby M, Garden OJ. Does antibiotic prophylaxis at the time of catheter insertion reduce the incidence of catheter-related sepsis in intravenous nutrition? J Hosp Infect 1985;6:419-425.

63. Ljungman P, Hagglund H, Bjorkstrand B, Lonnqvist B, Ringden O. Peroperative teicoplanin for prevention of gram-positive infections in neutropenic patients with indwelling central venous catheters: a randomized, controlled study. Support Care Cancer 1997;5:485-488.

Final Comment to Chapter 16

Infections due to central venous catheters are common and lead to substantial morbidity and healthcare costs. Several practices will likely reduce the incidence of this common patient safety problem, including the use of maximum sterile barrier precautions during catheter insertion, use of catheters coated with antibacterial or antiseptic agents, and use of chlorhexidine gluconate at the insertion site. Additionally, use of heparin and tunneling of the central venous catheter may prove to be effective in reducing CR-BSI. However, the relative efficacy of these interventions is unclear. Also, a clear and formal delineation of the economic consequences of combining several of these patient safety practices is necessary.

Return to Contents
Proceed to Next Chapter

 

The information on this page is archived and provided for reference purposes only.

 

AHRQ Advancing Excellence in Health Care