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Can a Patient Become Resistant to Chlorhexidine Mouthrinse?

What amount and what length of regimen are too much?

QUESTION: Can a patient become resistant to chlorhexidine mouthrinse? What amount and what length of regimen are too much?

ANSWER: Antiseptic mouthrinses have well-documented benefits as adjuncts to mechanical plaque removal methods for reducing supragingival plaque and gingivitis. Antiseptic mouthrinses reviewed by the United States Food and Drug Administration and those carrying the American Dental Association Seal of Acceptance have been proven in clinical trials to be safe and effective. Most patients can improve their oral health by incorporating an efficacious mouthrinse into their daily regimen of brushing and flossing.1,2

Many question whether antiseptic mouthrinses produce selective effects against pathogens only, or if chronic use will kill or inhibit normal flora, increasing the risk for repopulation of the mouth with opportunistic and/or more pathogenic/resistant organisms. This concern seems logical, given the microbial diversity and complex dynamics of the oral cavity, and widespread concerns about increased microbial resistance. If normal flora were adversely affected, the clinical results would most certainly be unfavorable.

We have known for more than 30 years that chronic use of antiseptic mouthrinses does not promote microbial resistance. Many clinical studies evaluated the potential for this phenomenon. Five studies document no adverse effects on supragingival dental plaque microflora after 6 months of continued use with 0.12% chlorhexidine gluconate (CHX) mouthrinse.3–7 In long-term studies of at least 6 months, dental plaque was harvested at baseline, at midpoint, and at the end of the trial. The microbial organisms and quantitative data were compiled and the minimum inhibitory concentration (MIC) for isolates was determined. The data from these investigations documented that the routine use of CHX mouthrinse on a long-term basis (6 months) was not associated with adverse shifts in plaque ecology, emergence of opportunistic pathogens or resistance strains, or changes in microbial susceptibility.3,4 Investigators from a more recent laboratory study reported that two of five strains of the periodontal pathogen, Porphyromonas gingivalis, may have the potential to develop resistance with prolonged exposure; however, this finding has not been reported in vivo by any other group.8 In fact, another laboratory study found that a number of tested CHX formulations were active against common oral organisms.9

Clinicians should feel confident that CHX mouthrinse is safe for patients as an adjunct to treating gingivitis. However, current recommendations stipulate that CHX mouthrinse use should be limited to 6 weeks, with patient re-evaluation to determine the need for continued therapy. Clinicians must also weigh side effects with long-term use against potential benefits, including staining, taste alteration, and supragingival calculus formation, which can negatively influence compliance. For some patients, the cost and inconvenience of using a prescription product may also be factors for consideration.


  1. DePaola LG, Spolarich AE. Safety and efficacy of antimicrobial mouthrinses in clinical practice. J Dent Hyg. 2007;81(Suppl Pt 2):13–25.
  2. Ciancio S. Biofilm dynamics at the gingival frontier. Int Dent J. 2010;60:200–203.
  3. Minah GE, DePaola LG, Overholser CD, et al. Effects of 6 months use of an antiseptic mouthrinse on supragingival dental plaque microflora. J Clin Periodontol. 1989;16:347–352.
  4. Walker C, Clark W, Tyler K, Ross N, Dills S. Evaluation of microbial shifts following long-term antiseptic mouthrinse use. J Dent Res. 1989;68:412.
  5. Emilson CG, Fornell J. Effect of toothbrushing with chlorhexidine gel on salivary microflora, oral hygiene, and caries. Scand J Dental Res. 1976;84:308–319.
  6. Schiott CR, Briner WW, Loe H. Two year oral use of chlorhexidine in man. II. The effect on the salivary bacterial flora. J Periodontal Res. 1976;11:145–152.
  7. Briner WW, Grossman E, Buckner RY, et al. Effect of chlorhexidine gluconate mouthrinse on plaque bacteria. J Periodontal Res. 1986;21(Suppl):44–52.
  8. Kulik EM, Waltimo T, Weiger R, et al. Development of resistance of mutans streptococci and Prophyromonas gingivalis to chlorhexidine digluconate and amine fluoride/ stannous fluoride-containing mouthrinses, in vitro. Clin Oral Investig. 2015;19:1547–1553.
  9. Eick S, Goltz S, Nietzsche S, Jentsch H, Pfister W. Efficacy of chlorhexidine digluconate-containing formulations and other mouthrinses against periodontopathogenic microorganisms. Quintessence Int. 2011;42:687–700.


The Ask the Expert column features answers to your most pressing clinical questions provided by Dimensions of Dental Hygiene’s online panel of key opinion leaders, including: Jacqueline J. Freudenthal, RDH, MHE, on anesthesia; Nancy K. Mann, RDH, MSEd, on cultural competency; Claudia Turcotte, CDA, RDH, MSDH, MSOSH, on ergonomics; Van B. Haywood, DMD, and Erin S. Boyleston, RDH, MS, on esthetic dentistry; Michele Carr, RDH, MA, and Rachel Kearney, RDH, MS, on ethics and risk management; Durinda Mattana, RDH, MS, on fluoride use; Kandis V. Garland, RDH, MS, on infection control; Mary Kaye Scaramucci, RDH, MS, on instrument sharpening; Stacy A. Matsuda, RDH, BS, MS, on instrumentation; Karen Davis, RDH, BSDH, on insurance coding; Cynthia Stegeman, EdD, RDH, RD, LD, CDE, on nutrition; Olga A.C. Ibsen, RDH, MS, on oral pathology; Jessica Y. Lee, DDS, MPH, PhD, on pediatric dentistry; Bryan J. Frantz, DMD, MS, and Timothy J. Hempton, DDS, on periodontal therapy; Ann Eshenaur Spolarich, RDH, PhD, on pharmacology; and Caren M. Barnes, RDH, MS, on polishing. Log on to to submit your question.

From Dimensions of Dental Hygiene. February 2019;17(2):46.

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