Chlorhexidine Gluconate topical

Pronunciation

Class: Local Anti-infectives, Miscellaneous
Chemical Name: N,N′′-Bis(4-chlorophenyl)-3,12-diimino- 2,4,11,13-tetraazatetradecanediimidamide di-d-gluconate
Molecular Formula: C22H30Cl2N10•2C6H12O7
CAS Number: 18472-51-0
Brands: Avagard, Betasept, Biopatch, Chlorostat, Hibiclens, Hibistat

Introduction

Cationic bisbiguanide; a topical anti-infective agent.1 4 5

Uses for Chlorhexidine Gluconate

Surgical Hand Antisepsis

Preoperative hand antisepsis in health-care personnel1 18 105 107 108 to inactivate microorganisms (normal and transient flora) present on the hands and forearms.5 18 104

Chlorhexidine gluconate 2 or 4% skin cleanser solutions have more persistent anti-infective activity compared with other available anti-infective cleansers.105

Surgical Site Preparation

Anti-infective skin cleanser for preoperative skin preparation at the surgical site.1 15 18 107

Preoperative Whole-body Disinfection

Anti-infective skin cleanser for patient preoperative showering and bathing5 18 35 36 37 39 44 to decrease bacterial flora on the skin.18

Slideshow: 18 Herbal Supplements with Risky Drug Interactions

Herbal and Dietary Supplements Deserve Your Attention

Hand Hygiene in Health-care Personnel

Routine hand hygiene in health-care personnel1 2 18 105 107 to prevent transmission of nosocomial infection.5 17 25 83 105

Considered an alternative for decontaminating hands; alcohol-based preparations are recommended instead for decontaminating hands (if they are not visibly soiled) since alcohol-based preparations are most effective for standard hand antisepsis by health-care personnel.105

Superficial Skin Wound and General Skin Cleansing

Used as a cleanser of superficial skin wounds and for general cleansing of skin.1 53 54 78

Should not be used routinely in wounds that involve more than the superficial layers of the skin.1 78

Advantage over alcohol because of a duration of action of 5–6 hours and retention of the drug’s activity in the presence of blood and organic material.1 5 54

Catheter Site Preparation and Catheter Site Care

Skin disinfection prior to insertion of intravascular, central venous, or arterial catheters and for postinsertion site care to prevent catheter-related infections in patients with vascular and nonvascular percutaneous devices.47 51 55 100 11

Chlorhexidine gluconate 2% solution is the preferred agent for such antisepsis.106

Burns

Management of burns to clean the affected area and prevent wound infection.4 5 56

Blood Collection Site Preparation

Skin disinfection prior to collection of venous blood cultures7 or blood donations.116

Genitourinary Uses

Periurethral cleansing prior to urinary catheterization.103

Topical lubricant on urinary catheters.3 5

Bladder irrigation5 57 104 in an attempt to decrease the incidence of bacteriuria and bacteremia associated with the use of indwelling catheters.3 5 103 (See Hypersensitivity Reactions under Cautions.)

Prevent maternal-fetal transmission of vaginal bacteria, including Streptococcus agalactiae (group B streptococci), to reduce maternal and neonatal infections.95 96 97 98 115

Chlorhexidine Gluconate Dosage and Administration

Administration

Topical Administration

Preparations are for external use only; avoid contact with the eyes, ears, or mouth.1 2 78 107 108

Apply solutions in a sudsing base (skin cleanser) and solutions in an alcohol base with emollients (hand rub) topically to the skin and hands.1 2 78 107 108

Do not use solutions in sudsing base on the face or head for preoperative skin preparation.1 78 107

Apply chlorhexidine containing dressings at the site of vascular and nonvascular percutaneous devices.111

Dosage

Adults

Surgical Hand Antisepsis
Chlorhexidine Gluconate Solution 2 or 4% (Skin Cleanser)
Topical

Wet hands and forearms with water.1 78 107 Apply approximately 5 mL of the skin cleanser onto the hands and rub into a copious lather by adding small amounts of water.1 78 107

Spread suds over the hands and forearms and scrub well with a wet brush for the time interval recommended by the manufacturer (e.g., 3 minutes).1 78 107

Pay particular attention to the nails, cuticles, and interdigital spaces; a separate nail cleaner may be used.1 78 107

After scrubbing, rinse the hands and forearms thoroughly under running water.1 78 107

Apply a second application (5 mL) and scrub the hands and forearms for an additional 3 minutes.1 78 107 Then rinse thoroughly with running water and dry with a sterile towel.1 18 78 107

Prolonged scrub times (e.g., 10 minutes) not necessary and may increase incidence of skin damage.105

Sponge/brush containing 4% skin cleanser: open package and remove nail cleaner.1 Wet hands with water and use nail cleaner under fingernails and to clean cuticles.1 Wet hands and forearms to elbows with warm water (avoid use of very cold or very warm water).1 Wet sponge side of sponge/brush; squeeze and pump immediately to work up adequate lather.1 Apply lather to hands and forearms using only sponge side of product; then start 3-minute scrub using brush side of product to scrub only nails, cuticles, and interdigital areas.1 Rinse hands and forearms thoroughly with warm water, then scrub for an additional 3 minutes using sponge side only.1 Rinse hands and forearms thoroughly with running water and dry with sterile towel.1

Chlorhexidine Gluconate 1% Solution in Alcohol Base (Hand Rub)
Topical

Wash hands, forearms, and nails with an unmedicated soap (without an anti-infective) and dry completely.105 108 Apply 2 mL of solution onto palm of one hand; dip fingertips of other hand into solution and massage under nails.108

Spread remaining solution over hand and forearms, up to just above the elbow, making certain to cover all surfaces.108

Repeat procedure using another 2 mL of solution using opposite hand.108

Finally, apply additional 2 mL of solution onto palm of either hand and reapply to both hands, up to wrists.108

Rub hands together briskly until all solution is rubbed into hands and forearms and dries completely; do not use towels to dry since this decreases solution efficacy.108

Hands and forearms should be completely dry prior to donning surgical gloves.105 108

Never use water in conjunction with the alcohol-based solution.108

Surgical Site Preparation
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)
Topical

Apply liberally to the incision site and swab for at least 2 minutes; dry with a sterile towel.1 78 107

Repeat procedure for an additional 2 minutes and dry area again with a sterile towel.1 78 107

Hand Hygiene in Health-care Personnel
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)
Topical

Wet hands with warm water (avoid use of very cold or very hot water); dispense approximately 5 mL of the skin cleanser into cupped hands.1 78 107 Work up a lather (do not use excessive pressure to produce additional lather) and wash hands for 15 seconds.1 78 Rinse hands thoroughly with warm water, then dry.1 78 107

Chlorhexidine Gluconate 0.5 or 1% in Alcohol Base (Hand Rub)
Topical

Hands must first be physically clean and dry before application of solution.2 108 Dispense approximately 5 mL of the 0.5% solution or 2 mL of 1% solution into cupped hands and rub vigorously until dry (about 15 seconds); pay particular attention to nails and interdigital spaces.2 108 Solution dries rapidly while hands are rubbed; do not use water or other toweling.2 108

Pledgets: vigorously rub hands with a hand wipe for approximately 15 seconds, paying particular attention to nails and interdigital spaces.2 Solution dries rapidly while hands are rubbed; do not use water or other toweling.2

Superficial Skin Wound and General Skin Cleansing
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)
Topical

Rinse the area thoroughly with water before application of the solution.1 78 107 Apply the minimum amount of skin cleanser to cover the skin or wound area.1 78 107 Wash the area gently with the skin cleanser, then thoroughly rinse again.1 78 107

Catheter Site Preparation and Catheter Site Care
Topical

Apply solution and air dry before catheter insertion.106

Dressing: Apply to the site using aseptic technique.111 Dressing may be left in place for up to 7 days.111 Consult manufacturer’s information for details.111

Cautions for Chlorhexidine Gluconate

Contraindications

  • Contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.1 2 78 107 108

Warnings/Precautions

Warnings

Topical Use

Skin cleanser and alcohol-based solutions are for external use only; do not use in eyes, ears, or mouth.1 2 78 107 108 Skin cleanser should not be used for preoperative skin preparation of the face or head.1

Skin cleanser and alcohol-based chlorhexidine solutions should not be used routinely on individuals who have wounds involving more than the superficial layers of the skin.1 78 107 108

Use with caution on mucous membranes and apply on wound surfaces at the lowest bactericidal concentration (0.05%) (not commercially available in the US) to decrease the risk of anaphylactic reactions.63

Avoid direct contact of the drug with brain tissue or meninges.1 105 107

Ocular and Otic Effects

Possible irreversible corneal damage after accidental ocular exposure.60

Do not touch eyes with hands that have been treated with chlorhexidine.108 If ocular contact occurs, rinse eye promptly and thoroughly with water.1 2 78 107 108

Possible sensorineural deafness after direct application for perioperative disinfection of the ear prior to vascular myringoplasty.1 5

Flammability

Alcohol-based preparations (Hibistat, Avagard) should not be exposed to excessive heat (i.e., temperatures exceeding 40°C); keep away from flames or devices that may generate an electric spark.2 108 These preparations dry rapidly as the hands are rubbed together2 108 and are no longer flammable after drying.108

Sensitivity Reactions

Hypersensitivity Reactions

Serious, systemic hypersensitivity reactions, including hypotension, tachycardia, shortness of breath, skin erythema, and anaphylaxis, have been reported with preparations applied topically to the skin3 4 63 64 66 or given intraurethrally,3 4 64 65 intranasally,67 or on central venous catheter (CVCs) impregnated with the drug.3 4 68 69

Dermatitis

Local contact dermatitis reported when chlorhexidine-impregnated dressings were used to cover CVC insertion site in neonates.3 62 100 May be severe, may require discontinuance of the chlorhexidine dressing, and have occurred most frequently in low birthweight neonates.62 100

General Precautions

Fabric Stains

Binds to many fabrics, particularly cotton, and may not be removed by washing.79 Permanent brown stain may occur if sufficient chlorine is present during washing.79 Consult manufacturer’s recommendations for laundering advice.79

Specific Populations

Pregnancy

Category B.b

Lactation

Unlikely to be distributed into human milk following topical or intravaginal application.71

Multiple episodes of bradycardia and cyanosis reported in a neonate when chlorhexidine was applied to the nursing mother’s breasts for prevention of mastitis.74 Wash nipples thoroughly with water prior to nursing if used for skin cleansing.71

Pediatric Use

Keep preparations out of the reach of children.1 2 107 108

Common Adverse Effects

Irritation, sensitization, generalized allergic reactions,1 2 4 5 100 107 108 118 especially when used in the genital area.1 2 78 107 108

Interactions for Chlorhexidine Gluconate

No formal drug interaction studies to date.1 2 3

Chlorhexidine Gluconate Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from GI tract4 or percutaneously following topical application to skin.1 4 5

Low concentrations appear to be absorbed systemically following intravaginal administration.71

Adsorbed onto outer layers of skin following topical application to intact skin, resulting in a persistent (residual) antimicrobial effect.1 5 6 14

In pregnant women who received a 2% solution intravaginally as a vaginal wash during labor, concentrations ranging from 0.01–0.083 mcg/mL were detected in the blood (limits of detection 0.01 mcg/mL) of approximately 33% of these women.71

Serum concentrations of 11 ng/mL reported in a neonate after oral exposure when chlorhexidine gluconate was used on the nursing mother’s nipples to prevent mastitis.74

Special Populations

Possible systemic absorption when topical preparations used as skin cleansers in neonates or infants.4 5 12 13

Distribution

Extent

Not known whether chlorhexidine crosses the placenta or is distributed into milk.a

Elimination

Elimination Route

If absorbed percutaneously following topical application to the skin, appears to be mainly excreted unchanged in feces.5

Stability

Storage

Topical

Dressing, Pledgets, Solution

Tight, light resistant containers; protect from excessive heat (i.e., >40°C).1 2 11

Keep alcohol-based preparations (Hibistat and Avagard) away from flames or devices that may generate an electric spark.2 108

Actions and Spectrum

  • Bacteriostatic or bactericidal in action, depending on concentration attained at site and susceptibility of organism.5 15

  • Cationic compound;5 6 adsorbed onto negatively charged cell surfaces of susceptible organisms, with specific and strong adsorption to certain phosphate-containing compounds.5 6 Integrity of the cell membrane is disrupted, resulting in increased permeability.5 6

  • Active against some aerobic and anaerobic gram-positive and gram-negative bacteria.1 2 4 5 6 102 Also has some activity against Chlamydia trachomatis,77 certain fungi,4 5 6 and certain viruses,4 5 52 but inactive against mycobacteria48 and generally inactive against bacterial spores.15

Advice to Patients

  • Importance of avoiding contact with eyes, ears, and mouth.1 2 78 107 108 If ocular contact occurs, rinse eye promptly and thoroughly with water to prevent irreversible injury.1 2 60 78 107 108

  • Avoid exposure to excessive heat (i.e., >40°C) with alcohol-based preparations (Hibistat, Avagard); keep away from flames or devices that may generate an electric spark.2 108

  • Importance of discontinuing drug and informing clinician if an allergic or hypersensitivity reaction occurs.1 2 108

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.71 93

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 2 108

  • Importance of informing patients of other important precautionary information. (See Cautions.)1 2 108

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Chlorhexidine Gluconate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Dressing

20% w/w

Biopatch

J & J

Pledgets (saturated with solution)

0.5% w/w with isopropyl alcohol 70%

Hibistat Hand Wipe

Regent Medical

Solution

0.5% w/w with isopropyl alcohol 70%

Hibistat Hand Rinse

Regent Medical

1% w/w with alcohol 61%

Avagard Hand Antiseptic

3M

2% w/w

Chlorostat Skin Cleaner and Surgical Scrub

King

4% w/v

Betasept Surgical Scrub

Purdue Frederick

Hibiclens Skin Cleanser

Regent Medical

Sponge/Brush

4% w/v

Hibiclens Skin Cleanser

Regent Medical

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Regent Medical. Information sheet for Hibiclens (chlorhexidine gluconate) antiseptic/antimicrobial skin cleanser and Hibiclens sponge/brush (undated). From website ().

2. AstraZeneca. Hibistat (chlorhexidine gluconate) germicidal hand rinse and Hibistat (chlorhexidine gluconate) germicidal handwipe prescribing information (undated). From website ().

3. Burlington DB. Potential hypersensitivity reactions to chlorhexidine-impregnated medical devices. FDA Public Health Notice. Rockville MD: Food and Drug Administration; 1998 Mar 11.

4. Parfitt K, ed. Martindale: the complete drug reference. 32nd ed. London: Pharmaceutical Press; 1999:1229-31.

5. Denton DW. Chlorhexidine. In: Block SS, ed. Disinfection, sterilization, and preservation. 4th edition. Philadelphia: Lea & Febiger; 1991:274-89.

6. Stuart Pharmaceuticals. Product information on Hibiclens (chlorhexidine gluconate) skin cleanser. Wilmington, DE.(undated)

7. Mimoz O, Karim A, Mercat A et al. Chlorhexidine compared with povidone-iodine as skin preparation before blood culture. Ann Intern Med. 1999; 131:834-7. [IDIS 437441] [PubMed 10610628]

8. Farndal O, Turnbull RS. A review of the literature on use of chlorhexidine in dentistry. J Am Dent Assoc. 1986; 112:863-9. [IDIS 216528] [PubMed 2940282]

9. Millns B, Martin MV, Field EA et al. The sensitivity to chlorhexidine and cetyl pyridinium chloride of staphylococci on the hands of dental students and theatre staff exposed to these disinfectants. J Hosp Infect. 1994; 26:99-104. [PubMed 7911154]

10. Barry AL, Fuchs PC, Brown SD. Lack of effect of antibiotic resistance on susceptibility of microorganisms to chlorhexidine gluconate or povidone iodine. Eur J Clin Microbiol Infect Dis. 1999; 18:920-1. [PubMed 10691210]

11. Regent Medical. Material safety data sheets for Hibiclens (chlorhexidine gluconate). From website ().

12. Cowen J, Ellis SH, McAinsh J. Absorption of chlorhexidine from the intact skin of newborn infants. Arch Dis Child. 1979; 54:379-83. [PubMed 475414]

13. Aggett PJ, Cooper LV, Ellis SH et al. Percutaneous absorption of chlorhexidine in neonatal cord care. Arch Dis Child. 1981; 56:878-80. [IDIS 143296] [PubMed 7305432]

14. Carret L, Reverdy ME, Lafforgue C et al. Kinetics of chlorhexidine on intact skin following a single application. Pathol Biol. 1997; 45:737-40. [PubMed 9538472]

15. Russell AD, Day MJ. Antibacterial activity of chlorhexidine. Hosp Infect. 1993; 25:229-38.

16. Nicoletti G, Boghossian V, Gurevitch F et al. The antimicrobial activity in vitro of chlorhexidine, a mixture of isothiazolinones (‘Kathon’ CG) and cetyl trimethyl ammonium bromide (CTAB). J Hosp Infect. 1993; 23:87-111. [PubMed 8097222]

17. Ford-Jones EL. Antiseptics, disinfectants, and sterilization. In: Kalant H and Roschlau WH, eds. Principles of medical pharmacology. 6th edition. New York: Oxford University Press; 1998:746-55.

18. Mangram AJ, Horan TC, Pearson ML et al. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999; 20:250-78. [PubMed 10219875]

19. Babb JT, Davies JG, Ayliffe GA. A test for evaluating surgical hand disinfection. J Hosp Infect. 1991; 18(Suppl B):41-9. [PubMed 1679446]

20. Bending JW. Surgical hand disinfection: comparison of 4% chlorhexidine detergent solution and 2% triclosan detergent solution. J Hosp Infect. 1990; 15:143-8. [PubMed 1969436]

21. Pereira LJ, Lee GM, Wade KJ. The effect of surgical handwashing routines on the microbial counts of operating room nurses. Am J Infect Control. 1990; 18:354-64. [PubMed 2285173]

22. Babb JR, Davies JG, Ayliffe GA. A test procedure for evaluating surgical hand disinfection. J Hosp Infect. 1991; 18(Suppl B):41-9. [PubMed 1679446]

23. Paulson DS. Comparative evaluation of five surgical hand scrub preparations. AORN J. 1994; 60:246,249-56. [PubMed 7944323]

24. Aly R, Maibach HI. Comparative evaluation of chlorhexidine gluconate (Hibiclens) and povidone-iodine (E-Z Scrub) sponge/brushes for presurgical hand scrubbing. Curr Ther Res. 1983; 34:740-5.

25. 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. [IDIS 298628] [PubMed 1285746]

26. Wade JJ, Casewell MW. The evaluation of residual antimicrobial activity on hands and its clinical relevance. J Hosp Infect. 1991; 18(Suppl B):23-8. [PubMed 1679443]

27. Ayliffe GA, Babb JR, Davies JG et al. Hand disinfection: a comparison of various agents in laboratory and ward studies. J Hosp Infect. 1988 11:226-43.

28. Faoagali JL, George N, Fong J et al. Comparison of the antibacterial efficacy of 4% chlorhexidine gluconate and 1% triclosan handwash products in an acute clinical ward. Am J Infect Control. 1999; 27:320-6. [PubMed 10433670]

29. Larson EL, Eke PI, Wilder MP et al. Quantity of soap as a variable in handwashing. Infect Control. 1987; 8:371-5. [PubMed 3654132]

30. Larson E, Mayur K, Laughon BA. Influence of two handwashing frequencies on reduction in colonizing flora with three handwashing products used by health care personnel. Am J Infect Control. 1989; 17:83-8. [PubMed 2729661]

31. Larson E, Leyden JJ, McGinley KJ et al. Physiologic and microbiologic changes in skin related to frequent handwashing. Infect Control. 1986; 7:59-63. [PubMed 3633879]

32. Paulson DS. Efficacy evaluation of a 4% chlorhexidine gluconate as a full-body shower wash. Am J Infect Control. 1993; 21:205-9. [PubMed 8239051]

33. Byrne DJ, Napier A, Phillips G et al. Effects of whole body disinfection on skin flora in patients undergoing elective surgery. J Hosp Infect. 1991; 17:217-22. [PubMed 1675650]

34. Byrne DJ, Napier A, Cuschieri A. Rationalizing whole body disinfection. J Hosp Infect. 1990; 15:183-7. [PubMed 1969442]

35. Garibaldi RA. Prevention of intraoperative wound contamination with chlorhexidine shower and scrub. J Hosp Infect. 1988; 11(Suppl B):5-9. [PubMed 2898503]

36. Hayek LJ, Emerson JM. Preoperative whole body disinfection—a controlled clinical study. J Hosp Infect. 1988; 11(Suppl B):15-9. [PubMed 2898499]

37. Garibaldi RA, Skolnick D, Lerer T et al. The impact of preoperative skin disinfection on preventing intraoperative wound contamination. Infect Control Hosp Epidemiol. 1988; 9:109-13. [PubMed 3351267]

38. Kaiser AB, Kernodle DS, Barg NL et al. Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers. Ann Thorac Surg. 1988; 45:35-8. [IDIS 238027] [PubMed 3337574]

39. Hayek LJ, Emerson JM, Gardner AM. A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on postoperative wound infection rates. J Hosp Infect. 1987; 10:165-72. [PubMed 2889770]

40. Wihlborg O. The effect of washing with chlorhexidine soap on wound infection rate in general surgery. A controlled study. Ann Chir Gynaecol. 1987; 76:263-5. [PubMed 3324917]

41. Leigh DA, Stronge JL, Marriner J et al. Total body bathing with ‘Hibiscrub’ (chlorhexidine) in surgical patients: a controlled trial. J Hosp Infect. 1983; 4:229-35. [PubMed 6195235]

42. Ayliffe GA, Noy MF, Babb JR et al. A comparison of pre-operative bathing with chlorhexidine-detergent and non-medicated soap in the prevention of wound infection. J Hosp Infect. 1983; 4:237-44. [PubMed 6195236]

43. Rotter ML, Larsen SO, Cooke EM et al et al. A comparison of the effects of preoperative whole-body bathing with detergent alone and with detergent containing chlorhexidine gluconate on the frequency of wound infections after clean surgery. J Hosp Infect. 1988; 11:310-20. [PubMed 2899582]

44. Earnshaw JJ, Berridge DC, Slack RC et al. Do prepoperative chlorhexidine baths reduce the risk of infection after vascular reconstruction? Eur J Vasc Surg. 1989; 3:323-6.

45. Aly R, Maibach HI. Comparative study on the antimicrobial effect of 0.5% chlorhexidine gluconate and 70% isopropyl alcohol on the normal flora of hands. Appl Environ Microbiol. 1979; 37:610-3. [PubMed 453833]

46. Larson EL, Eke PI, Laughon BE. Efficacy of alcohol-based hand rinses under frequent-use conditions. Antimicrob Agents Chemother. 1986; 30:542-4. [PubMed 3789690]

47. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of providone-iodine, alcohol, and chlorhexidine for prevention of infection associated with central venous and arterial catheters. Lancet. 1991; 338:339-43. [IDIS 284105] [PubMed 1677698]

48. Rikimaru T, Kondo M, Kondo S et al. Efficacy of common antiseptics against mycobacteria. Int J Tuberc Lung Dis. 2000; 4:570-6. [PubMed 10864189]

49. Darouiche RO, Raad II, Heard SO et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med. 1999; 340:1-8. [IDIS 417707] [PubMed 9878638]

50. Veenstra DL, Saint S, Saha S et al. Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection. JAMA. 1999; 281:261-7. [IDIS 417497] [PubMed 9918482]

51. Mermel LA. Prevention of intravascular catheter-related infections. Ann Intern Med. 2000; 132:391-402. [IDIS 448160] [PubMed 10691590]

52. Montefiori DC, Robinson WE Jr, Modliszewski A et al. Effective inactivation of human immunodeficiency virus with chlorhexidine antiseptics containing detergents and alcohol. J Hosp Infect. 1990; 15:279-82. [PubMed 1971635]

53. Hayward PF, Morrison WA. Current concepts in wound dressings. Australian Prescriber. 1996; 19:11-13.

54. Laufman H. Current use of skin and wound cleansers and antiseptics. Am J Surg. 1989; 157: 3:359-65. [IDIS 308909] [PubMed 2645807]

55. 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; 31:1001-7. [IDIS 456002] [PubMed 11049783]

56. Monafo WW, West MA. Current treatment recommendations for topical burn therapy. Drugs. 1990; 40:364-73. [PubMed 2226220]

57. Ball AJ, Thomas WC, Gillesie WA et al. Bladder irrigation with chlorhexidine for the prevention of urinary infection after transurethral operations: a prospective controlled study. J Urol. 1987; 138:491-4. [IDIS 234474] [PubMed 3625846]

58. Russell AD, McDonnell G. Concentration: a major factor in studying biocidal action. J Hosp Infect. 2000; 44:1-3. [PubMed 10633046]

59. Aursnes J. Cochlear damage from chlorhexidine in guinea pigs. Acta Otolaryngol. 1981; 92:259-71. [PubMed 7324895]

60. Tabor E, Bostwick DC, Evans CC et al. Corneal damage due to eye contact with chlorhexidine gluconate. JAMA. 1989; 261:557-8. [IDIS 249661] [PubMed 2909794]

61. MacRae SM, Brown B, Edelhauser HF. The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol. 1984; 97:221-32. [PubMed 6696033]

62. Garland JS, Alex CP, Mueller CD et al. Local reactions to a chlorhexidine gluconate-impregnated antimicrobial dressing in very low birth weight infants. Pediatr Infect Dis J. 1996; 15:912-4. [IDIS 373256] [PubMed 8895928]

63. Okano M, Nomura M, Hata S et al. Anaphylactic symptoms due to chlorhexidine gluconate. Arch Dermatol. 1989; 125:50-2. [IDIS 249624] [PubMed 2910207]

64. Snellman E, Rantanen T. Severe anaphylaxis after a chlorhexidine bath. J Am Acad Dermatol. 1999; 40:771-2. [IDIS 428002] [PubMed 10321611]

65. Yong D, Parker FC, Foran SM. Severe allergic reactions and intra-urethral chlorhexidine gluconate. Med J Aust. 1995; 162:257-8. [IDIS 344854] [PubMed 7891607]

66. Evans RJ. Acute anaphylaxis due to topical chlorhexidine acetate. BMJ. 1992; 304:686. [IDIS 293607] [PubMed 1571641]

67. Chisholm DG, Calder I, Peterson D et al. Intranasal chlorhexidine resulting in anaphylactic circulatory arrest. BMJ. 1997; 315:785. [IDIS 392651] [PubMed 9345172]

68. Terazawa E, Shimonaka H, Nagase K. Severe anaphylactic reaction due to a chlorhexidine-impregnated central venous catheter. Anesthesiology. 1998; 89:1296-8. [IDIS 417095] [PubMed 9822040]

69. Oda T, Hamasaki J, Kanda N et al. Anaphylactic shock induced by an antiseptic-coated central venous catheter. Anesthesiology. 1997; 87:1242-3. [IDIS 396954] [PubMed 9366479]

70. Sakagami Y, Yamazaki H, Ogasawara N et al. The evaluation of genotoxic activities of disinfectants and their metabolites by umu test. Mutat Res. 1988; 209:155-60. [PubMed 3143068]

71. Briggs GG, Freeman RK, Sumner JY. Drugs in pregnancy and lactation. 5th ed. Baltimore: Williams & Wilkins; 1998.

72. Ellenhorn MJ, Schonwald S, Ordog G et al. eds. Ellenhorn’s medical toxicology. 2nd ed. Baltimore: Williams & Wilkins; 1997.

73. Massano G, Ciocatto E, Rosabianca C et al. Striking aminotransferase rise after chlorhexidine self-poisoning. Lancet. 1982; 1:289. [IDIS 144932] [PubMed 6120309]

74. Quinn MW, Bini RM. Bradycardia associated with chlorhexidine spray. Arch Dis Child. 1989; 64:892-3. [IDIS 256065] [PubMed 2774629]

75. Tattawasart U, Maillard JY, Furr JR et al. Development of resistance to chlorhexidine diacetate and cetylpyridinium chloride in Pseudomonas stutzeri and changes in antibiotic susceptibility. J Hosp Infect. 1999; 42:219-29. [PubMed 10439995]

76. Rosenberg A, Alatary SD, Peterson AF. Safety and efficacy of the antiseptic chlorhexidine gluconate. Surg Gynecol Obstet. 1976; 789-92.

77. Lampe MF, Ballweber LM, Stamm WE. Susceptibility of Chlamydia trachomatis to chlorhexidine gluconate gel. Antimicrob Agents Chemother. 1998; 42:1726-30. [PubMed 9661012]

78. Purdue Frederick. Betasept (chlorhexidine gluconate) surgical scrub 4% prescribing information. In: Physician’s desk reference. 56th ed. Montvale NJ: Medical Economics Company Inc; 2002:2895.

79. Regent Medical. Hibiclens laundry instructions. From website ().

80. Garvey LH, Petersen JR, Husum B. Anaphylactic reactions in anaesthetised patients—four cases of chlorhexidine allergy. Acta Anaesthesiol Scand. 2001; 45:1290-4. [PubMed 11736685]

81. Lauerma AI. Simultaneous immediate and delayed hypersensitivity to chlorhexidine digluconate. Contact Derm. 2001; 44:59. [PubMed 11156034]

82. Goroncy-Bermes P, Schouten MA, Voss A. In vitro activity of a nonmedicated handwash product, chlorhexidine, and an alcohol-based hand disinfectant against multiply resistant gram-positive microorganisms. Infect Control Hosp Epidemiol. 2001; 22:194-6. [PubMed 11379706]

83. Guilhermetti M, Hernandes SED, Fukushigue Y et al. Effectiveness of hand-cleansing agents for removing methicillin-resistant Staphylococcus aureus from contaminated hands. Infect Control Hosp Epidemiol. 2001; 22:105-8. [PubMed 11232870]

84. Knight BA, Puy R, Douglass J et al. Chlorhexidine anaphylaxis: a case report and review of the literature. Intern Med J. 2001; 31:436-7. [PubMed 11584911]

85. Baqui AAMA, Kelley JI, Jabra-Rizk MA et al. In vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1. J Clin Periodontol. 2001; 28:610-16. [PubMed 11422581]

86. Block C, Robenshtok E, Simhon A et al. Evaluation of chlorhexidine and povidone iodine activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis using a surface test. J Hosp Infect. 2000; 46:147-52. [PubMed 11049709]

87. Suller MTE, Russell AD. Antibiotic and biocide resistance in methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus. J Hosp Infect. 1999; 43:281-91. [PubMed 10658804]

88. Kampf G, Hofer M, Wendt C. Efficacy of hand disinfectants against vancomycin-resistant enterococci in vitro. J Hosp Infect. 1999; 42:143-50. [PubMed 10389064]

89. Kampf G, Jarosch R, Ruden H. Limited effectiveness of chlorhexidine based hand disinfectants against methicillin-resistant Staphylococcus aureus (MRSA). J Hosp Infect. 1998; 38:297-303. [PubMed 9602978]

90. Ellepola AN, Samaranayake LP. The effect of brief exposure to sub-therapeutic concentrations of chlorhexidine gluconate on the germ tube formation of oral Candida albicans and its relationship to post-antifungal effect. Oral Dis. 2000; 6:166-71. [PubMed 10822360]

91. MacNeill S, Rindler E, Walker A et al. Effects of tetracycline hydrochloride and chlorhexidine gluconate on Candida albicans. An in vitro study. J Clin Periodontol. 1997; 24:753-60. [PubMed 9350560]

92. Meiller TF, Kelley JI, Jabra-Rizk MA et al. In vitro studies of the efficacy of antimicrobials against fungi. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001; 91:663-70.

93. Colgate Oral Pharmaceuticals. PerioGard (chlorhexidine gluconate) oral rinse prescribing information. Canton, MA; 1999 Jul.

94. Gaillard P, Mwanyumba F, Verhofstede C et al. Vaginal lavage with chlorhexidine during labour to reduce mother-to-child HIV transmission: clinical trial in Mombasa, Kenya. AIDS. 2001; 15:389-96. [PubMed 11273219]

95. Stray-Pedersen B, Bergan T, Hafstad A et al. Vaginal disinfection with chlorhexidine during childbirth. Int J Antimicrob Agents. 1999; 12:245-51. [PubMed 10461843]

96. Taha TE, Biggar RJ, Broadhead RL et al. Effect of cleansing the birth canal with antiseptic solution on maternal and newborn morbidity and mortality in Malawi: clinical trial. BMJ. 1997; 315:216-9. [IDIS 389177] [PubMed 9253269]

97. Rouse DJ, Hauth JC, Andrews WW et al. Chlorhexidine vaginal irrigation for the prevention of peripartal infection: a placebo-controlled randomized clinical trial. Am J Obstet Gynecol. 1997; 176:617-22. [IDIS 383440] [PubMed 9077616]

98. Bigger RJ, Miotti PG, Taha TE et al. Perinatal intervention trial in Africa: effect of a birth canal cleansing intervention to prevent HIV transmission. Lancet. 1996; 347:1647-50. [IDIS 366599] [PubMed 8642957]

99. Adriaanse AH, Kollee LA, Muytjens HL et al. Randomized study of vaginal chlorhexidine disinfection during labor to prevent vertical transmission of group B streptococci. Eur J Obstet Gynecol Reprod Biol. 1995; 61:135-41. [PubMed 7556834]

100. Garland JS, Alex CP, Mueller CD et al. A randomized trial comparing povidone-iodine to a chlorhexidine gluconate-impregnated dressing for prevention of central venous catheter infections in neonates. Pediatrics. 2001; 107:1431-6. [IDIS 466274] [PubMed 11389271]

101. Odore R, Colombatti Valle V, Re G. Efficacy of chlorhexidine against some strains of cultured and clinically isolated microorganisms. Vet Res Commun. 2000; 24:229-38. [PubMed 10836268]

102. Rabe LK, Hillier SL. Effect of chlorhexidine on genital microflora, Neisseria gonorrhoeae, and Trichomonas vaginalis in vitro. Sex Transm Dis. 2000; 74-8.

103. Webster J, Hood RH, Burridge CA et al. Water or antiseptic for periurethral cleaning before urinary catheterization: a randomized controlled trial. Am J Infect Control. 2001; 29:389-94. [PubMed 11743486]

104. Adesanya AA, Osegbe DN, Amaku EO. The use of intermittent chlorhexidine bladder irrigation in the prevention of post-prostatectomy infective complications. Int Urol Nephrol. 1993; 25:359-67. [PubMed 7506239]

105. Centers for Disease Control and Prevention. Guideline for hand hygiene in health-care settings: recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR Morb Mortal Wkly Rep. 2002; 51(No. RR-16):1-45.

106. Centers for Disease Control and Prevention. Guidelines for the prevention of intravascular catheter-related infections. MMWR Morb Mortal Wkly Rep. 2002; 51(No. RR-10):1-26.

107. Jones Pharma. Chlorostat (chlorhexidine gluconate 2% w/w) antimicrobial skin cleaner and surgical scrub. St. Louis, Mo. 1999 Jun. 108.

108. 3M Pharmaceuticals. Avagard (chlorhexidine gluconate 1% solution and ethyl alcohol 61% w/w) surgical and healthcare personnel hand antiseptic with moisturizers. St. Paul, MN. 2001.

109. Mulberry G, Snyder AT, Heilman J et al. Evaluation of a waterless, scrubless, chlorhexidine gluconate/ethanol surgical scrub for antimicrobial efficacy. Am J Infect Control. 2001: 29:377-82.

110. Chalyakunapruk N, Veenstra DL, Lipsky BA et al. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med. 2002; 136:792-801. [IDIS 481472] [PubMed 12044127]

111. Johnson and Johnson. Biopatch antimicrobial dressing. From the Johnson and Johnson web site: (Accessed 2002 Dec.)

112. Case DE. Safety of Hibitane. I. Laboratory experiments. J Clin Periodontol. 1977; 4:68-72.

113. Anderson MH, Bales DJ, Omnell KA. Modern-management of dental caries: the cutting edge is not the dental bur. J Amer Dent Assoc. 1993; 124:37-44.

114. Maki DG, Mermel LA, Kluger D et al. The efficacy of a chlorhexidine-impregnated sponge (Biopatch) for the prevention of intravascular catheter-related infection – a prospective, randomized, controlled multicenter study. [abstract 1430]. In: Program and abstracts of the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto). Washington, DC: American Society for Microbiology, 2000:422.

115. Faccinetti F, Piccinini F, Mordini B et al. Chlorhexidine vaginal flushings versus systemic ampicillin in the prevention of vertical transmission of neonatal group B streptococcus, at term. J Matern Fetal Neonatal Med. 2002; 11:84-8. [PubMed 12375548]

116. Lee CK, Ho PL, Chan NK et al. Impact of donor arm skin disinfection on the bacterial contamination rate of platelet concentrates. Vox Sang. 2002; 83:204-8. [PubMed 12366760]

117. Brooks SE, Walczak MA, Hameed R et al. Chlorhexidine resistance in antibiotic-resistant bacteria isolated from the surfaces of dispensers of soap containing chlorhexidine. Infect Control Hosp Epidemiol. 2002; 23:692-5. [PubMed 12452299]

118. Cimiotti JP, Marmur ES, Nesin M et al. Adverse reactions associated with an alcohol-based hand antiseptic among nurses in a neonatal intensive care unit. Am J Infect Control. 2003; 31:43-8. [PubMed 12548257]

119. Walder B, Pittet D, Tramer MR. Prevention of bloodstream infections with central venous catheters treated with anti-infective agents depends on catheter type and insertion time: evidence from a meta-analysis. Infect Control Hosp Epidemiol. 2002; 23:748-56. [PubMed 12517018]

a. AHFS Drug Information 2004. McEvoy GK, ed. Chlorhexidine Gluconate. American Society of Health-System Pharmacists; 2004:3385-90.

b. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Baltimore, MD: Williams & Wilkins; 2002:237.

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