Cetylpyridinium Chloride: Mechanism of Action, Antimicrobial Efficacy in Biofilms, and Potential Risks of Resistance

Abstract

Antimicrobial resistance is a serious issue for public health care all over the world. While resistance toward antibiotics has attracted strong interest among researchers and the general public over the last 2 decades, the directly related problem of resistance toward antiseptics and biocides has been somewhat left untended. In the field of dentistry, antiseptics are routinely used in professional care, but they are also included in lots of oral care products such as mouthwashes or dentifrices, which are easily available for consumers over-the-counter. Despite this fact, there is little awareness among the dental community about potential risks of the widespread, unreflected, and potentially even needless use of antiseptics in oral care. Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which was first described in 1939, is one of the most commonly used antiseptics in oral care products and included in a wide range of over-the-counter products such as mouthwashes and dentifrices. The aim of the present review is to summarize the current literature on CPC, particularly focusing on its mechanism of action, its antimicrobial efficacy toward biofilms, and on potential risks of resistance toward this antiseptic as well as underlying mechanisms. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward antiseptics in general.

Limited antimicrobial efficacy of oral care antiseptics in microcosm biofilms and phenotypic adaptation of bacteria upon repeated exposure

“…Currently, a wide range of antiseptic mouthwashes is available as over-the-counter consumer products, comprising various antiseptics or essential oils [15,16,19]. While the bis-biguanide chlorhexidine digluconate (CHX) is considered the goldstandard antiseptic in oral care [20,21], also quaternary ammonium compounds (QACs) such as cetylpyridinium chloride (CPC), benzalkonium chloride (BAC) and dequalinium chloride (DQC), or the bis-biguanide alexidine dihydrochloride (ALX) have been investigated [15,16,19,22].…”

“…Although it is well established that these antiseptics provide clinical benefits in terms of reducing oral biofilm formation and managing gingivitis (mostly by decreasing the salivary bacterial load), their antimicrobial efficacy toward preformed, mature oral biofilms may be limited when applied for clinically realistic treatment periods [21][22][23]. For instance, treatment with 0.2% CHX for 1 min only affected the outer layers of biofilms formed in situ for 48 h, as it was shown in a classic study by confocal laser scanning microscopy combined with LIVE/DEAD staining [24].…”

“…For instance, treatment with 0.2% CHX for 1 min only affected the outer layers of biofilms formed in situ for 48 h, as it was shown in a classic study by confocal laser scanning microscopy combined with LIVE/DEAD staining [24]. Therefore, clinical use of an antiseptic mouthwash may result in concentration gradients in oral biofilms, with lower biofilm strata being exposed to sub-inhibitory concentrations of the antiseptics [21,22]. Upon multiple exposures to such sub-inhibitory concentrations, oral bacteria may be able to phenotypically adapt toward these antiseptics by employing analogous mechanisms as known for resistance against antibiotics [21,22,[25][26][27].…”

“…Therefore, clinical use of an antiseptic mouthwash may result in concentration gradients in oral biofilms, with lower biofilm strata being exposed to sub-inhibitory concentrations of the antiseptics [21,22]. Upon multiple exposures to such sub-inhibitory concentrations, oral bacteria may be able to phenotypically adapt toward these antiseptics by employing analogous mechanisms as known for resistance against antibiotics [21,22,[25][26][27]. Since the oral cavity may be considered potential reservoir of resistance genes, antimicrobial resistance may easily be spread among oral biofilm bacteria via horizontal gene transfer [28][29][30].…”

Rhamnolipid coating reduces microbial biofilm formation on titanium implants: an in-vitro study

“…Such strategies can act through different mechanisms including anti-adhesive treatments able to modify implant surface energy and bacterial adhesion, surface coatings with molecules having biocidal or photocatalytic activity, or capable to sustain a controlled release of antimicrobial and/or antiseptic agents at the implant/tissue interface [16][17][18]. Despite the antimicrobial effectiveness of some implant coatings, there are relevant limitations such as a limited e cacy over time, the possible induction of antibiotic and/or antiseptic resistance, a decreased biocompatibility or even the cytotoxicity of some antimicrobial agents [19][20][21][22].…”