Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic

Abstract

Olanexidine gluconate [1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate] (development code OPB-2045G) is a new monobiguanide compound with bactericidal activity. In this study, we assessed its spectrum of bactericidal activity and mechanism of action. The minimal bactericidal concentrations of the compound for 30-, 60-, and 180-s exposures were determined with the microdilution method using a neutralizer against 320 bacterial strains from culture collections and clinical isolates. Based on the results, the estimated bactericidal olanexidine concentrations with 180-s exposures were 869 g/ml for Gram-positive cocci (155 strains), 109 g/ml for Gram-positive bacilli (29 strains), and 434 g/ml for Gram-negative bacteria (136 strains). Olanexidine was active against a wide range of bacteria, especially Gram-positive cocci, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, and had a spectrum of bactericidal activity comparable to that of commercial antiseptics, such as chlorhexidine and povidone-iodine. In vitro experiments exploring its mechanism of action indicated that olanexidine (i) interacts with the bacterial surface molecules, such as lipopolysaccharide and lipoteichoic acid, (ii) disrupts the cell membranes of liposomes, which are artificial bacterial membrane models, (iii) enhances the membrane permeability of Escherichia coli, (iv) disrupts the membrane integrity of S. aureus, and (v) denatures proteins at relatively high concentrations (>160 g/ ml). These results indicate that olanexidine probably binds to the cell membrane, disrupts membrane integrity, and its bacteriostatic and bactericidal effects are caused by irreversible leakage of intracellular components. At relatively high concentrations, olanexidine aggregates cells by denaturing proteins. This mechanism differs slightly from that of a similar biguanide compound, chlorhexidine.

Virucidal Efficacy of Olanexidine Gluconate as a Hand Antiseptic Against Human Norovirus

“…Thus, the difference in the virucidal efficacy of OLG-HR and other antiseptics is thought to be due to differences in the capsid structure stability by a trivial difference in the amino acid sequence structure, which needs to be addressed in a future study. The mechanism of action of virucidal efficacy of OLG-HR against human norovirus is not well understood, but it is known that at relatively high concentrations, olanexidine aggregates the cells through a protein-denaturing effect (Hagi et al 2015;Sakagami et al 2000). Furthermore, the virucidal effect of OLG-HR against non-enveloped viruses such as feline calicivirus and bacteriophage MS2 has been found to be stronger under basic conditions (data not shown).…”

“…Olanexidine gluconate is a novel antimicrobial compound developed by Otsuka Pharmaceutical Factory, Inc. and has been used in Japan clinically for preoperative skin preparation [Product name: Olanedine Antiseptic Solution 1.5% (OLG)] (Hagi et al 2015;Inoue et al 2015;Nakata et al 2017). The virucidal efficacy of OLG against feline calicivirus at 60-s and 10 min were 0.60, and 2.85, respectively (unpublished data).…”

“…Because European Committee for Standardization states that "the product shall demonstrate at least a decimal log reduction of 4 in virus titre" (EN 14476 2013), the virucidal activity of OLG against a non-enveloped virus is not enough as well as other biguanide compounds (Iwasawa et al 2012;Sickbert-Bennett et al 2005). The mode of action of OLG is similar to that of chlorhexidine gluconate, a biguanide antiseptic, but OLG has also been confirmed to have a stronger protein denaturation effect than chlorhexidine gluconate (Hagi et al 2015).…”

Evaluation of <i>in Vitro</i> Bactericidal Activity of 1.5% Olanexidine Gluconate, a Novel Biguanide Antiseptic Agent

“…Among these bacteria, emergence of CHG tolerant-bacteria has become a worldwide healthcare concern. 7,8) Olanexidine gluconate, a novel biguanide antiseptic agent, was launched in 2015 in Japan for use as skin disinfectant for surgical sites. Olanexidine gluconate exerts strong and fastacting bactericidal activity against wide range of bacteria.…”

Allergic contact dermatitis caused by Olanedine® (olanexidine gluconate), a new antiseptic

“…799787‐53‐4; Fig. ), which has been shown to exert a significant bactericidal effect against a wide range of bacteria, especially gram‐positive cocci, including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant enterococci . We present the first 2 cases of allergic contact dermatitis (ACD) caused by this antiseptic.…”