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

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 µg/ml for Gram-positive cocci (155 strains), 109 µg/ml for Gram-positive bacilli (29 strains), and 434 µg/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 µg/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.

Human noroviruses are the major cause of non-bacterial acute gastroenteritis worldwide. Since no therapeutic agent has been proven to prevent human norovirus infection yet, preventive healthcare interventions to block the infection routes play an important role in infection control. One of the possible infection routes of human noroviruses are through contaminated hands, but no hand antiseptics have been proven effective. Olanexidine gluconate is a new biguanide compound that has already been approved for sale as an antiseptic for the surgical field in Japan. A new hand antiseptic was developed using olanexidine gluconate in this study, and its virucidal efficacy against human noroviruses was evaluated using modified RT-qPCR that can account for genome derived from intact viruses using RNase A and photo-reactive intercalators. We tested the virucidal efficacy of five materials; two olanexidine gluconate antiseptics (hand rub formulation and surgical field formulation), two kinds of ethanol solutions at different pH (approx. 3 or 7), and a base component of olanexidine gluconate hand rub formulation against 11 human norovirus genotypes by culture-independent methods. The infectivity of murine norovirus (MNV), a surrogate for human norovirus, was significantly reduced after use of the antiseptics. The olanexidine gluconate hand rub demonstrated the strongest virucidal efficacy against human norovirus among the five tested materials. This study showed that olanexidine gluconate has the potential to become a strong tool for the prevention of human norovirus infection.

Evaluation of fast-acting bactericidal activity and substantivity of an antiseptic agent, olanexidine gluconate, using an ex vivo skin model.

PURPOSE: We assessed the fast-acting bactericidal activity and substantivity of olanexidine gluconate (OLG) to investigate its remaining bactericidal activity on the skin after rinsing and drying by using an ex vivo Yucatan micropig (YMP) skin model. METHODOLOGY: The fast-acting bactericidal activity was evaluated in pigskin models inoculated with methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, vancomycin-resistant Enterococcus faecalis (VRE), Acinetobacter baumannii, Corynebacterium minutissimum and Cutibacterium acnes. To evaluate substantivity, the YMP skin piece first had 1.5 % OLG, chlorhexidine gluconate (CHG) formulations or 10 % povidone-iodine (PVP-I) applied to it, and was then rinsed with distilled water, incubated for 4, 6, 8 or 12 h and inoculated with the test bacteria (MRSA, S. epidermidis and VRE). The viable bacteria remaining at 1 min of exposure of bacteria were counted to measure the quantity of antiseptic molecules retaining bactericidal activity. To determine the factors contributing to the substantivity, the stratum corneum (SC) of the YMP skin that had had OLG or CHG applied to it was exfoliated using a tape-stripping method and the amount of antiseptic was quantitated. RESULTS: OLG showed a fast-acting bactericidal activity that was similar to or stronger than that of CHG formulations up to a concentration of 1 % and PVP-I with a short exposure time of 30 s, and substantivity until 12 h after rinsing, whereas the other antiseptics hardly showed any substantivity. There was 2.8 times or more OLG in the SC than CHG. CONCLUSION: OLG has fast-acting activity and substantivity, which are required properties for an antiseptic, and is useful for preventing infections.

Effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys.

PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: OPB-2045G), against transient or resident bacterial flora on the skin of cynomolgus monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine. After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts were measured again and log10 reductions were calculated. In addition, we determined the bactericidal effects on the skin contaminated with blood before or after applying the antiseptics. RESULTS: In the non-blood-contaminated condition, the mean log10 reductions of olanexidine at doses of 1-2 % were significantly higher than those of saline (negative control), but did not significantly differ from those of 0.5 % chlorhexidine and 10 % povidone-iodine at either time point. But olanexidine was significantly more effective at both time points than chlorhexidine and povidone-iodine when applied after the site was contaminated with blood. Olanexidine was also significantly more effective than chlorhexidine and as effective as or more effective than povidone-iodine at both time points when skin was contaminated with blood after the antiseptics were applied. CONCLUSION: The bactericidal effects of olanexidine were comparable to those of commercial antiseptics such as chlorhexidine and povidone-iodine in non-blood-contaminated conditions. More importantly, the effect of olanexidine was hardly affected by blood unlike commercial antiseptics. Thus, it is considered that olanexidine has a favourable property for skin preparation in various types of surgical treatments.

Central Retinal Artery Occlusion after the Endovascular Treatment of Unruptured Ophthalmic Artery Aneurysm: A Case Report and a Literature Review.

Endovascular coil embolization for ophthalmic artery (OphA) aneurysms has a risk of occlusion of the OphA, which can lead to loss of vision. The authors report a patient with unruptured OphA aneurysm which treated with endovascular coiling and were complicated by blindness due to OphA thromboembolic occlusion after the procedure. The OphA successfully recanalized using local intra-arterial fibrinolysis with complete regain of visual acuity. The risk of visual loss due to thromboembolic complications cannot be ignored during endovascular coiling of the OphA aneurysm despite of good retrograde flow during OphA occlusion test using a balloon catheter. Rapid intervention is required for recovering visual disturbance in such a situation.

Novel antiseptic compound OPB-2045G shows potent bactericidal activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus both in vitro and in vivo: a pilot study in animals.

There is a need for new compounds to effectively treat methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The novel monobiguanide compound 1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate (OPB-2045G) has potential bactericidal activity. We sought to elucidate the potency of OPB-2045G bactericidal activity against MRSA and VRE compared to those of chlorhexidine digluconate (CHG) and povidone iodine (PVP-I). In vitro bactericidal activity was analysed using minimum bactericidal concentration (MBC) as the index. The in vivo bactericidal efficacy of OPB-2045G was examined by determining MRSA and VRE contamination of the normal dorsal skin of mice following removal of hair. After a 3 min treatment period, the MBC of OPB-2045G was lower than that of CHG and PVP-I against standard strains and clinical isolates. Additionally, in our in vivo mouse model, the in vivo bactericidal activity of 1.5 % OPB-2045G (a clinically relevant dose) was higher than that of 0.5 % CHG and equivalent to that of 10 % PVP-I against MRSA. Similarly, the in vivo bactericidal activity of OPB-2045G was higher than that of 0.5 % CHG and 10 % PVP-I against VRE. OPB-2045G showed more potent bactericidal activity against MRSA and VRE both in vitro and in vivo compared to CHG and PVP-I, indicating that OPB-2045G may provide better protection against health care-associated infections caused by these pathogens.

Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats.

NO-1886 is a lipoprotein lipase (LPL) activator. Administration of NO-1886 results in an increase in plasma high-density lipoprotein cholesterol (HDL-C) and a decrease in plasma triglyceride (TG) levels. The aim of this study was to ascertain whether NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin (STZ)-induced diabetic rats. Administration of NO-1886 resulted in increased plasma HDL-C levels and decreased TG levels without affecting total cholesterol and glucose levels in the diabetic rats. NO-1886 dose-dependently decreased liver TG contents and cholesterol contents, resulting in improvement of fatty liver. NO-1886 also reduced plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that accompany fatty liver. The liver cholesterol contents were inversely correlated with plasma HDL-C levels (r = -0.5862, P <.001) and were positively correlated with plasma TG levels (r = 0.4083, P <.003). The liver TG contents were inversely correlated with plasma HDL-C levels (r = -0.6195, P <.001) and were positively correlated with plasma TG levels (r = 0.5837, P <.001). There was no correlation between plasma cholesterol levels, and cholesterol and TG contents in liver. These results indicate that reducing plasma TG levels and elevating in HDL-C levels may result in improving fatty liver.

Benign esophageal schwannoma compressing the trachea in pregnancy.

A rare case of esophageal schwannoma compressing the trachea in pregnancy is presented. A 29-year-old pregnant woman was hospitalized due to severe dyspnea. Imaging studies revealed a homogeneous tumor (8 cm in diameter) in the posterior mediastinum with compression of the lower trachea. After an uneventful cesarean section, the patient underwent a mini-axillary thoracotomy with video-assisted thoracic surgery. The tumor arose from within the muscular layers of the esophagus and was enucleated by gentle blunt dissection. Pathologic and immunohistochemical examinations revealed a benign esophageal schwannoma.

The relationship between lipoprotein lipase activity and respiratory quotient of rats in circadian rhythms.

Plasma lipid levels and lipoprotein lipase (LPL) are known to follow circadian rhythms in rats. However, very little information is available on the variations in respiratory quotient (RQ) during the 24-h period in rats. The aims of this study were to provide an overall view of the effects of circadian rhythm on RQ and to determine the relationship of LPL and RQ with metabolic parameters in these animals. Male rats were fed ad libitum and were kept under a 12 :12-h light-dark cycle. Rats were killed every 2 h over a 24-h period for measurement of metabolic parameters and tissue LPL activity. The RQ was measured every 4 h over the same 24-h period. The gastric contents increased during the dark phase and decreased during the light phase. For the metabolic parameters, circadian rhythms were detected for plasma glucose, triglycerides, high-density lipoprotein cholesterol and non esterified free fatty acids, but not for plasma total cholesterol or phospholipids. The RQ and adipose tissue LPL activity increased during the dark phase, while skeletal muscle LPL activity decreased during this phase. The RQ was inversely correlated with skeletal muscle LPL activity (r = -0.880) and positively correlated with adipose tissue LPL activity (r = 0.937). These results appear to show that rats tend toward consumption of fat by accelerating fat oxidation, resulting in suppression of fat accumulation in the light phase, while tending toward fat accumulation by the suppression of fat oxidation in the dark phase.