What is the mechanism of action of chlorhexidine (CHX), an antimicrobial agent?

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Last updated: May 9, 2025View editorial policy

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From the Guidelines

Chlorhexidine works primarily by disrupting bacterial cell membranes, causing leakage of cellular components and inhibiting membrane-bound enzymes, leading to a bacteriostatic or bactericidal effect, depending on the concentration. This antiseptic agent carries a positive charge that attracts it to the negatively charged bacterial cell surfaces, where it binds to phospholipids in the cell membrane 1. At low concentrations, chlorhexidine causes leakage of low-molecular-weight cellular components and inhibits membrane-bound enzymes, creating a bacteriostatic effect. At higher concentrations, it penetrates the cell membrane completely, causing precipitation of cellular contents and cell death, making it bactericidal.

Key Characteristics of Chlorhexidine

  • Chlorhexidine demonstrates substantivity, meaning it binds to oral tissues and skin, allowing for prolonged antimicrobial activity for up to 12 hours after application 1
  • It has a broad spectrum of activity against gram-positive and gram-negative bacteria, some viruses, and fungi, though it is less effective against bacterial spores
  • Chlorhexidine is commonly used as a 0.12% or 0.2% oral rinse for dental applications, and as a 2-4% solution for skin antisepsis before surgical procedures

Important Considerations for Use

  • For optimal effectiveness in oral applications, chlorhexidine should be used after brushing, with at least 30 minutes between brushing and rinsing, as toothpaste surfactants can inactivate chlorhexidine 1
  • The prolonged contact time and persistent activity make chlorhexidine particularly valuable for infection control in both dental and medical settings
  • Chlorhexidine has been shown to be more effective than povidone iodine in reducing bacterial colonization and infection rates in certain clinical settings 1

From the FDA Drug Label

CLINICAL PHARMACOLOGY Paroex ® provides antimicrobial activity during oral rinsing. The mechanism of action of chlorhexidine is not explicitly stated in the drug label, but it is known to provide antimicrobial activity.

  • The label mentions a general reduction of counts of certain assayed bacteria, both aerobic and anaerobic, but does not explain how this reduction occurs.
  • It is implied that chlorhexidine gluconate has antibacterial properties, but the exact mechanism is not described. 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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