Evidence of incompatibility for topical anionic agents used in conjunction with chlorhexidine gluconate: A systematic review

Gary Tran, Thy N Huynh, Finola M Bruins, Najeah Ahmad, William A Budris, Alba Posligua, Josh A Hammel, Beatrice Nardone, Dennis P West


Chlorhexidine gluconate (CHG) is a widely used antiseptic agent for skin and wound disinfection. The cationic properties of CHG may allow its inactivation and precipitation by anionic agents in commonly used topical agents. We conducted a systematic review by searching through PubMed, Cochrane Library, and Web of Science databases and selected original research articles reporting on CHG incompatibility, defined as inactivation or precipitation. The search yielded 22 publications that demonstrated CHG incompatibility via: 1) reduced antibacterial activity (carbomer, acrylates/C10-C30 alkyl acrylate crosspolymer, dentin, bovine serum albumin, copolymer M239144, sodium lauryl sulfate, heat-killed microbes, triethanolamine, and bark cork); and 2) visible precipitate formation (sodium hypochlorite, EDTA, saline, ethanol, andnystatin). Only three publications reported on CHG incompatibility in dermatology, specifically for carbomer, triethanolamine, and acrylates/C10-C30 alkyl acrylate crosspolymer. Although limited evidence linking CHG incompatibility and anionic agents exists, clinicians should carefully consider the nature of topical agents used if CHG is concurrently applied. Increased awareness of CHG incompatibility may result in better antibacterial activity thus ensuring optimal patient management.


chlorhexidine; incompatibility; inactivation; skin; reduced antibacterial activity; precipitation; systematic review

Included Database


McDonnell G, Russell AD. Antiseptics and disinfectants: Activity, action, and resistance. Clin Microbiol Rev 1999; 12(1): 147–79.

Abdallah C. Perioperative chlorhexidine allergy: Is it serious? J Anaesthesiol Clin Pharmacol 2015; 31(2): 152– 154. doi: 10.4103/0970-9185.155140.

Jones CG. Chlorhexidine: Is it still the gold standard? Periodontol 2000 1997; 15(1): 55–62. doi: 10.1111/j.1600-0757.1997.tb00105.x.

Aly R, Maibach HI. Comparative study on the antimicrobial effect of 0.5% chlorhexidine gluconate and 70% iso-propyl alcohol on the normal flora of hands. Appl Environ Microbiol 1979; 37(3): 610–613.

Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009; 151(4): 264–269. doi: 10.7326/0003-4819-151-4-200908180-00135.

Kaiser N, Klein D, Karanja P, Greten Z, Newman J. Inac-tivation of chlorhexidine gluconate on skin by incompatible alcohol hand sanitizing gels. Am J Infect Control 2009; 37(7): 569–573. doi: 10.1016/j.ajic.2008.12.008.

Benson L, LeBlanc D, Bush L, White J. The effects of surfactant systems and moisturizing products on the residual activity of a chlorhexidine gluconate hand wash using a pigskin substrate. Infect Control Hosp Epidemiol 1990; 11(2): 67–70. doi: 10.2307/30144264.

Walsh B, Blakemore PH, Drabu YJ. The effect of hand cream on the antibacterial activity of chlorhexidine gluconate. J Hosp Infect 1987; 9(1): 30–33. doi: 10.1016/0195-6701(87)90091-0.

Portenier I, Haapasalo H, Ørstavik D, Yamauchi M, Haapasalo M. Inactivation of the antibacterial activity of iodine potassium iodide and chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix, type-I collagen, and heat-killed microbial whole cells. J Endod 2002; 28(9): 634–637. doi: 10.1097/00004770-200209000-00002.

Haapasalo HK, Sirén EK, Waltimo TMT, Ørstavik D, Haapasalo MPP. Inactivation of local root canal medicaments by dentine: An in vitro study. IntEndod J 2000; 33(2): 126–131. doi: 10.1046/j.1365-2591.2000.00291.x.

Portenier I, Haapasalo H, Rye A, Waltimo T, Ørst- avik D, et al. Inactivation of root canal medicaments by dentine, hydroxylapatite and bovine serum albumin. Int Endod J 2001; 34(3): 184–188. doi: 10.1046/j.1365-2591.2001.00366.x.

Mohammadi Z, Shalavi S. The effect of heat-killed Candida albicans and dentin powder on the antibacterial activity of chlorhexidine solution. Iran Endod J 2012; 7(2): 63–67.

Claydon N, Addy M, Ridge D, Jackson R. An evaluation of an antiadhesive copolymer agent on plaque inhibition by chlorhexidine. J Clin Periodontol 1996; 23(10): 952–954. doi: 10.1111/j.1600-051X.1996.tb00517.x.

Barkvoll P, Rølla G, Svendsen K. Interaction between chlorhexidine digluconate and sodium lauryl sulfate in vivo. J Clin Periodontol 1989; 16(9): 593–595.

doi: 10.1111/j.1600-051X.1989.tb02143.x.

Linton KB, George E. Inactivation of chlorhexidine ("hibitane") by bark corks. Lancet 1966; 1(7451): 1353–1355. doi: 10.1016/S0140-6736(66)92141-6.

Prado M, Santos Júnior HMS, Rezende CM,Pinto AC, Faria RB, et al. Interactions between irrigants commonly used in endodontic practice: A chemical analysis. J Endod 2013; 39(4): 505–510. doi: 10.1016/j.joen.2012.11.050.

Rossi-Fedele G, Doğramaci EJ, Guastalli AR, Steier L, de Figueiredo JAP. Antagonistic interactions between sodium hypochlorite, chlorhexidine, EDTA, and citric acid. J Endod 2012; 38(4): 426–431. doi: 10.1016/j.joen.2012.01.006.

Shenoy A, Bolla N, Sayish, Sarath RK, Ram CHS, et al. Assessment of precipitate formation on interaction of irrigants used in different combinations: An in vitro study. Indian J Dent Res 2013; 24(4): 451–455. doi: 10.4103/0970-9290.118392.

Gasic J, Popovic J, Živković S, Petrovic A, Barac R, et al. Ultrastructural analysis of the root canal walls after simultaneous irrigation of different sodium hypochlorite concentration and 0.2% chlorhexidine gluconate. Microsc Res Tech 2012; 75(8): 1099–1103. doi: 10.1002/jemt.22036.

Krishnamurthy S, Sudhakaran S. Evaluation and preven-tion of the precipitate formed on interaction between sodium hypochlorite and chlorhexidine. J Endod 2010; 36(7): 1154–1157. doi: 10.1016/j.joen.2010.01.012.

Akisue E, Tomita VS, Gavini G, de Figueiredo JAP. Effect of the combination of sodium hypochlorite and chlorhexidine on dentinal permeability and scanning elect-ron microscopy precipitate observation. J Endod 2010; 36(5): 847–850. doi: 10.1016/j.joen.2009.11.019.

Bui TB, Baumgartner JC, Mitchell JC. Evaluation of the interaction between sodium hypochlorite and chlorhexidine gluconate and its effect on root dentin. J Endod 2008; 34(2): 181–185. doi: 10.1016/j.joen.2007.11.006.

Cintra LTA, Watanabe S, Samuel RO, da Silva Facundo AC, de Azevedo Queiroz ÍO, et al. The use of NaOCl in combination with CHX produces cytotoxic product. Clin Oral Investig 2014; 18(3): 935–940. doi: 10.1007/s00784-013-1049-5.

Nowicki JB, Sem DS. An in vitro spectroscopic analysis to determine the chemical composition of the precipitate formed by mixing sodium hypochlorite and chlorhexidine. J Endod 2011; 37(7): 983–988. doi: 10.1016/j.joen.2011.03.033.

Basrani BR, Manek S, Sodhi RNS, Fillery E, Manzur A. Interaction between sodium hypochlorite and chlorhexidine gluconate. J Endod 2007; 33(8): 966–969. doi: 10.1016/j.joen.2007.04.001.

Rasimick BJ, Nekich M, Hladek MM, Musikant BL, Deutsch AS. Interaction between chlorhexidine digluconate and EDTA. J Endod 2008; 34(12): 1521–1523. doi: 10.1016/j.joen.2008.08.039.

Barkvoll P, Attramadal A. Effect of nystatin and chlorhexidine digluconate on Candida albicans. Oral Surg Oral Med Oral Pathol 1989; 67(3): 279–281. doi: 10.1016/0030-4220(89)90354-X.

Fiume MM, Heldreth B, Bergfeld WF, Belsito DV, Hill RA, et al. Safety assessment of triethanolamine and tri-ethanolamine-containing ingredients as used in cosmetics. Int J Toxicol 2013; 32(3 Suppl): 59S–83S. doi: 10.1177/1091581813488804.

Cosmetic Ingredient Review Expert Panel. Annual review of cosmetic ingredient safety assessments – 2001/2002. Int J Toxicol 2003; 22(Suppl 1): 1–35.

Cosmetic Ingredient Review [Internet]. Final Safety Assessment: Crosslinked alkyl acrylates as used in cosmetics. [cited 2015 December 15]. Available from:


Maki DG, Ringer M, Alvarado CJ, Ringer M. Prospective randomised trial of povidone-iodine, alcohol, and chlor-hexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338(8763): 339–343. doi: 10.1016/0140-6736(91)90479-9.

Darouiche RO, Wall MJ Jr, Itani KMF, Otterson MF, Webb AL, et al. Chlorhexidine-alcohol versus povidone- iodine for surgical-site antisepsis. N Engl J Med 2010; 362(1): 18–26. doi: 10.1056/NEJMoa0810988.

Macias JH, Arreguin V, Munoz JM, Alvarez JA, Mosqueda JL, et al. Chlorhexidine is a better antiseptic than povidone iodine and sodium hypochlorite because of its substantive effect. Am J Infect Control 2013; 41(7): 634– 637. doi: 10.1016/j.ajic.2012.10.002.

Popovich KJ, Lyles R, Hayes R, Hota B, Trick W, et al. Relationship between chlorhexidine gluconate skin con-centration and microbial density on the skin of critically ill patients bathed daily with chlorhexidine gluconate. Infect Control Hosp Epidemiol 2012; 33(9): 889–896. doi: 10.1086/667371.

Adams D, Quayum M, Worthington T, Lambert P, Elliott T. Evaluation of a 2% chlorhexidine gluconate in 70% isopropyl alcohol skin disinfectant. J Hosp Infect 2005; 61(4): 287–290. doi: 10.1016/j.jhin.2005.05.015.

DeBaun B. Evaluation of the antimicrobial prope- rties of an alcohol-free 2% chlorhexidine gluconate solution. AORN J 2008; 87(5): 925–933. doi: 10.1016/j.aorn.2008.02.001.

Rutter JD, Angiulo K, Macinga DR. Measuring residual activity of topical antimicrobials: Is the residual activity of chlorhexidine an artefact of laboratory methods? J Ho¬sp Infect 2014; 88(2): 113–115. doi: 10.1016/j.jhin.2014.06.010.

Marino C, Cohen M. Washington State hospital survey 2000: Gloves, handwashing agents, and moisturizers. Am J Infect Control 2001; 29(6): 422–424. doi: 10.1067/mic.2001.117298.

DOI: http://dx.doi.org/10.18282/jsd.v6.i1.21


  • There are currently no refbacks.