Evaluation of the active concentration of two disinfectants based on glutaraldehyde and benzalkonium chloride and antimicrobial activity in vitro against Salmonella Heidelberg and Salmonella Typhimurium

Biosecurity, cleaning and disinfection of swine and poultry facilities are fundamental for the reduction of pathogenic microorganisms of importance for public and animal health. The objective of this work was to compare the levels of active ingredient described on the label and the real levels detected in high-performance liquid chromatography (HPLC) of two disinfectants., then evaluate the antimicrobial activity since, following the Germicidal Sanitizing Action and Disinfectant Detergent (Official Method AOAC 960.09) in four different dilutions with the presence of 3% organic matter during 15 min of contact, against Salmonella Heidelberg and Salmonella Typhimurium (ST). The product "A" presents active levels of agreement according to the label. The content of quantified assets for product "B" was lower than that recorded on the label. The disinfectant "A" was effective in microbiological evaluation while the disinfectant "B" had microbiocidal activity compromised by the deficit of assets.

Anti-glaucoma agents-induced pseudodendritic keratitis presumed to be herpetic simplex keratitis: a clinical case series.

Anti-glaucoma agents-induced corneal toxicity may be misdiagnosed as herpetic simplex keratitis (HSK). In our study, nineteen glaucoma patients were presumed to have HSK before referral. Corneal lesions were classified into (I) linear pseudodendritic lesions formed by elevated opacified cells, (II) linear pseudodendritic lesions formed by grouped superficial punctate keratitis (SPK), (III) satellite full-thickness epithelial defects, (IV) satellite lesions formed by elevated opacified cells, and (V) geographic lesions formed by grouped SPK. We observed thirty-one events, with 15 in the lower and 16 in the central corneas. There were 21 (67.7%) type II, five (16.1%) type V, two (6.5%) of each for types III and IV, and one (3.2%) type I events. Among linear lesions (types I and II), 17 (77.3%) had horizontal and 5 (22.7%) had curvilinear orientations. Exposure duration to the last-added anti-glaucoma agent was three days to 14.5 years. About half of the events (16/31, 51.6%) used prostaglandin analogues, and 30/31 (96.8%) applied benzalkonium chloride (BAK)-containing agents. All lesions resolved within two months after decreasing offending medications or enhancing protection of ocular surface. In conclusion, anti-glaucoma agents-induced pseudodendritic keratitis presents majorly in central-lower cornea as horizontally linear lesions, and BAK-containing agents are observed in the most events.

Induction of mucosal immunity by pulmonary administration of a cell-targeting nanoparticle.

We previously found that a nanoparticle constructed with an antigen, benzalkonium chloride (BK) and γ-polyglutamic acid (γ-PGA) showed high Th1 and Th2-type immune induction after subcutaneous administration. For prophylaxis of respiratory infections, however, mucosal immunity should be induced. In this study, we investigated the effect of pulmonary administration of a nanoparticle comprising ovalbumin (OVA) as a model antigen, BK, and γ-PGA on induction of mucosal immunity in the lungs and serum. The complex was strongly taken up by RAW264.7 and DC2.4cells. After pulmonary administration, lung retention was longer for the OVA/BK/γ-PGA complex than for OVA alone. OVA-specific serum immunoglobulin (Ig)G was highly induced by the complex. High IgG and IgA levels were also induced in the bronchoalveolar lavage fluid, and in vivo toxicities were not observed. In conclusion, we effectively and safely induced mucosal immunity by pulmonary administration of an OVA/BK/γ-PGA complex.

Targeting Antibacterial Effect and Promoting of Skin Wound Healing After Infected with Methicillin-Resistant Staphylococcus aureus for the Novel Polyvinyl Alcohol Nanoparticles.

INTRODUCTION: Topical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective. METHODS: The novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied. RESULTS: These novel nanoparticles were found to have a significant antibacterial activity (p<0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 µg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity. CONCLUSION: Taken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds.

Systemic absorption of benzalkonium chloride after maximal use of a consumer antiseptic wash product.

An in vivo pharmacokinetic study was conducted using consumer antiseptic wash containing 0.13% benzalkonium chloride (BAC) to assess the effect of dermal absorption on long-term systemic exposure to BAC. The objective of the study was to determine blood levels of BAC under maximal use conditions. Subjects were enlisted to wash their hands 60 s with soap containing 0.13% BAC 30 times per day over an 8-9 h time period for 5 consecutive days. The test product with the highest absorption potential was selected based on market share and results from in vitro permeation testing. Blood plasma was collected from subjects on 32 occasions over the 6-day study period. Plasma samples were analyzed for the C12 and C14 homologs of BAC using LC-MS/MS with a lower limit of quantitation (LLOQ) of 106.9 and 32.6 ng/L, respectively. For the 32 subjects, C12 homolog was detected above the LLOQ in only four of 1,024 plasma samples at 117.8-191.7 ng/L, and C14 homolog was detected in only one sample at 59.5 ng/L. Consequently, systemic exposure to BAC in antimicrobial soap is very low and below the level of concern identified by the U.S. Food and Drug Administration (500 ng/L) even under maximal use conditions.

NCX 1741, a Novel Nitric Oxide-Donating Phosphodiesterase-5 Inhibitor, Exerts Rapid and Long-Lasting Intraocular Pressure-Lowering in Cynomolgus Monkeys.

Purpose: We studied the IOP-lowering effects of NCX 1741, a novel nitric oxide (NO)-donating derivative of the phosphodiesterase type-5 inhibitor, avanafil, in Cynomolgus monkey with laser-induced ocular hypertension (OHT-monkeys). NCX 1193 (NO-donating moiety), NCX 1744 (NCX 1741 without ester nitrate moiety), and travoprost (PGF2α analogue) were used for comparison. Ocular exposure after NCX 1741 dosing also was addressed. Methods: Vehicle (phosphate buffer pH 6.0, Kolliphor® 5%, DMSO 0.3%, benzalkonium chloride 0.02%), NCX 1741, NCX 1193, NCX 1744, or travoprost were instilled (30 µL; single dose) masked and conscious IOPs were measured by pneumatonometry. LC-MS/MS-based methods were employed to monitor ocular exposure of NCX 1741 and main metabolites after ocular dosing in New Zealand White rabbits. Results: NCX 1741 (2.2%, 0.8 µmol/eye) lowered IOP with an Emax (ΔΔIOP, IOP change vs. pre-dose and vehicle) between 5 and 8 h post-dosing (ΔΔIOP5h, -5.3 ± 2.0 mmHg and ΔΔIOP8h, -6.0 ± 2.1 mmHg). Conversely, equimolar (0.47%, 0.8 µmol/eye) NCX 1193 IOP-lowering effects were maximal 3 h post-dosing (ΔΔIOP3h, -4.7 ± 1.6 mmHg) and declined thereafter (ΔΔIOP5h, -1.6 ± 1.1 mmHg). In a follow-up study, NCX 1741 (1.5%, 0.5 µmol/eye) was more effective than NCX 1744 despite a similar duration. Further, NCX 1741 was as effective as travoprost (0.1%, 0.06 µmol/eye) at 5 and 8 h post-dosing (travoprost, ΔΔIOP5h, -3.4 ± 2.2 mmHg and ΔΔIOP8h, -4.9 ± 1.3 mmHg) but had shorter duration (NCX 1741, ΔΔIOP24h, -1.5 ± 1.1 mmHg; travoprost, ΔΔIOP24h, -7.1 ± 2.8 mmHg). NCX 1741 resulted in significant aqueous humor exposure, as determined by the levels of the main metabolite, avanafil. Conclusions: NCX 1741 rapidly and effectively lowers IOP in OHT-monkeys for several hours post-dosing. How these effects translate in humans is still to be defined.

Kinetics and distribution of benzalkonium compounds with different alkyl chain length following intravenous administration in rats.

Benzalkonium chloride is widely used in disinfectants. Several toxicological and fatal cases have been reported; however, little is known about its kinetics and distribution. We investigated the kinetic characteristics and distribution of benzalkonium cation (BZK) based on the length of the alkyl chains C12, C14, and C16. Rats were treated intravenously with BZK solution (dose, 13.9 mg/kg) containing equal amounts of the three homologues. Kinetic parameters in the blood were assessed, and BZK distribution in the blood and tissues was examined both in rapid intravenous (IV) and drip intravenous (DIV) administrations. BZK concentrations were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). BZK with longer alkyl chains showed lower elimination tendencies and remained in the blood for a longer duration. Concentrations of BZK were higher in the heart, lung, spleen, and kidney than those in the blood, and lower in the brain and fat. In both the IV and DIV groups, the lung, liver, spleen, and fat samples showed higher concentrations of the longer alkyl chains (BZK-C12 < -C14 < -C16), and the opposite trend was observed in the kidney (BZK-C16 < -C14 < -C12). Only the heart and muscle samples displayed the homologues in ratios comparable to the original administered solutions. Differences between IV and DIV groups could be identified by comparing concentrations of BZK homologues in the heart, lung, spleen, and kidney samples. We found that the kinetics and distribution of BZK were influenced by the alkyl chain length, and analysing each BZK homologues in blood and tissue samples may provide useful information.

High-Frequency Application of Cationic Agents Containing Lubricant Eye Drops Causes Cumulative Corneal Toxicity in an Ex Vivo Eye Irritation Test Model.

Purpose: High-frequency applied cetalkonium chloride (CAC) and benzalkonium chloride (BAC) 0.02% did not hamper corneal healing in a living rabbit model of induced corneal erosion. In contrast, the ex vivo eye irritation test (EVEIT) shows inhibition of healing for these substances. In a systematic ex vivo reproduction of the in vivo experiments, we discuss the background of these differences. Methods: Excised rabbit corneas (n = 5 per group) were cultured in artificial anterior chambers (EVEIT). Four erosions were induced for each cornea before starting regular 21 installations/day over 3 days of (1) CAC containing eye drops (Cationorm®), (2) 0.02% BAC. Corneal fluorescein staining, quantification of glucose-/lactate consumption, and histology were performed. Results: BAC 0.02% treated corneas showed increased epithelial lesions from 10.13 ± 0.65 mm2 to 10 ± 0.8 mm2 on day 0, to 86.82 ± 5.18 mm2 (P < 0.0001) by day 3. After a trend toward smaller lesions for CAC on day 1, erosion sizes increased significantly by day 3 from 9.82 ± 0.30 mm2 to 29.51 ± 16.87 mm2 (P < 0.05). For 1 cornea, corneal erosions nearly disappeared on day 3 (0.89 mm2). Corneal lactate increased significantly for BAC and CAC, whereas glucose concentrations were unchanged. Histology revealed disintegration of the corneal structures for both compounds. Conclusions: The data underline the EVEIT as a predictive toxicity test to show side effects in a time-compressed manner. The consistency of these predictions was previously demonstrated by the EVEIT for BAC, phosphate buffer, and others. The EVEIT is suited for a chronic application prediction of tolerability and toxic side effects of eye drops in particular, and other chemicals in general.

Influence of timolol, benzalkonium-preserved timolol, and benzalkonium-preserved brimonidine on oxidative stress biomarkers in the tear film.

PURPOSE: The objective of this study was to investigate the influence of topical preservative-free timolol, benzalkonium chloride(BAC)-preserved timolol, BAC-preserved timolol, and BAC-preserved brimonidine on total protein concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response, and Oxidative Stress Index (OSI) in the tear film. METHODS: The patients were divided into four groups: group C (n = 25)-control group-subjects who did not use topical antiglaucoma medications, group T (n = 17)-patients using topical preservative-free timolol, group T + BAC (n = 24)-patients using topical BAC-preserved timolol, and group BR + BAC (n = 19)-patients using topical BAC-preserved brimonidine. RESULTS: The SOD, CAT, and GPx activities as well as AOPP, TOS, and OSI were found to be higher in the tear film of patients treated with BAC-preserved topical timolol or brimonidine in comparison with patients treated with preservative-free timolol or patients who did not use antiglaucoma topical medications. CONCLUSIONS: This indicates that using BAC-preserved topical medications increases oxidative stress in the tear film and may, in the long-term, contribute to the clinical presentation of dry eye disease.

Effects of Benzalkonium Chloride and Preservative-Free Composition on the Corneal Epithelium Cells.

Purpose: Benzalkonium Chloride (BAK) is reported to have the potential to damage the cornea. We developed a composition with broad-spectrum antimicrobial activity without preservatives by combining trometamol, boric acid, and ethylenediaminetetraacetic acid (TBE). This study aimed at evaluating the corneal damage caused by TBE and comparing it with that caused by BAK. Methods: SV40-immortalized human corneal epithelial cell line (HCE-T) was treated with BAK or TBE, and the cell viability was measured. The exposure time that caused 50% cell death (CDT50) was calculated. Transepithelial electrical resistance (TEER) was measured before and after treatment with BAK or TBE. Occludin was detected with immunostaining and Western blotting after treatment with BAK or TBE. The effect of BAK or TBE on membrane-associated mucins was evaluated with rose bengal (RB) staining. Results: In the BAK group, cell viability decreased in a dose-dependent manner. The viability of the TBE group was significantly greater than that of the BAK group. The CDT50 of the TBE group is greater than that of the BAK groups. In the BAK groups, the recovery of TEER was delayed in a dose-dependent manner, whereas in the TBE group, the recovery occurred earlier. Localization of occludin was disrupted, and the amount of occludin was significantly reduced among the cells exposed to BAK. The area stained with RB in the BAK groups increased, whereas that in the TBE group did not increase. Conclusion: These results suggest that the application of TBE would be useful for developing preservative-free ophthalmic preparations that offer both sufficient safety and antimicrobial activity.

Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections.

BACKGROUND: Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. This is an update of a Cochrane Review first published in 2010 and subsequently updated in 2012, twice in 2014, in 2017 and 2018. OBJECTIVES: To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We also assessed the side effects of vaginal cleansing solutions to determine adverse events associated with the intervention. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (7 July 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. Cluster-RCTs were eligible for inclusion, but we did not identify any. We excluded trials that utilized vaginal preparation during labor or that did not use antibiotic surgical prophylaxis. We also excluded any trials using a cross-over design. We included trials published in abstract form only if sufficient information was present in the abstract on methods and outcomes to analyze. DATA COLLECTION AND ANALYSIS: At least three of the review authors independently assessed eligibility of the studies. Two review authors were assigned to extract study characteristics, quality assessments, and data from eligible studies. MAIN RESULTS: We included 21 trials, reporting results for 7038 women evaluating the effects of vaginal cleansing (17 using povidone-iodine, 3 chlorhexidine, 1 benzalkonium chloride) on post-cesarean infectious morbidity. Trials used vaginal preparations administered by sponge sticks, douches, or soaked gauze wipes. The control groups were typically no vaginal preparation (17 trials) or the use of a saline vaginal preparation (4 trials). One trial did not report on any outcomes of interest. Trials were performed in 10 different countries (Saudi Arabia, Pakistan, Iran, Thailand, Turkey, USA, Egypt, UK, Kenya and India). The overall risk of bias was low for areas of attrition, reporting, and other bias. About half of the trials had low risk of selection bias, with most of the remainder rated as unclear. Due to lack of blinding, we rated performance bias as high risk in nearly one-third of the trials, low risk in one-third, and unclear in one-third. Vaginal preparation with antiseptic solution immediately before cesarean delivery probably reduces the incidence of post-cesarean endometritis from 7.1% in control groups to 3.1% in vaginal cleansing groups (average risk ratio (aRR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; 20 trials, 6918 women; moderate-certainty evidence). This reduction in endometritis was seen for both iodine-based solutions and chlorhexidine-based solutions. Risks of postoperative fever and postoperative wound infection are also probably reduced by vaginal antiseptic preparation (fever: aRR 0.64, 0.50 to 0.82; 16 trials, 6163 women; and wound infection: RR 0.62, 95% CI 0.50 to 0.77; 18 trials, 6385 women; both moderate-certainty evidence). Two trials found that there may be a lower risk of a composite outcome of wound complication or endometritis in women receiving preoperative vaginal preparation (RR 0.46, 95% CI 0.26 to 0.82; 2 trials, 499 women; low-certainty evidence). No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing. Subgroup analysis suggested a greater effect with vaginal preparations for those women in labour versus those not in labour for four out of five outcomes examined (post-cesarean endometritis; postoperative fever; postoperative wound infection; composite wound complication or endometritis). This apparent difference needs to be investigated further in future trials. We did not observe any subgroup differences between women with ruptured membranes and women with intact membranes. AUTHORS' CONCLUSIONS: Vaginal preparation with povidone-iodine or chlorhexidine solution compared to saline or not cleansing immediately before cesarean delivery probably reduces the risk of post-cesarean endometritis, postoperative fever, and postoperative wound infection. Subgroup analysis found that these benefits were typically present whether iodine-based or chlorhexidine-based solutions were used and when women were in labor before the cesarean. The suggested benefit in women in labor needs further investigation in future trials. There was moderate-certainty evidence using GRADE for all reported outcomes, with downgrading decisions based on limitations in study design or imprecision. As a simple intervention, providers may consider implementing preoperative vaginal cleansing with povidone-iodine or chlorhexidine before performing cesarean deliveries. Future research on this intervention being incorporated into bundles of care plans for women receiving cesarean delivery will be needed.

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma.

BACKGROUND AND OBJECTIVES: The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. METHODS: We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A P value <.05 was considered significant. RESULTS: A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .001). CONCLUSIONS: BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization.

Topical hyaluronan alone promotes corneal epithelial cell migration whereas combination with benzalkonium chloride impairs epithelial wound healing.

Purpose: To evaluate the effects of topical hyaluronan (HA) on corneal epithelial wound healing when administered with or without benzalkonium chloride (BAC).Methods: A cultured human corneal epithelial cell line (HCE-T) was subjected to in vitro scratch assays and in situ epithelial migration was evaluated in organ-cultured rabbit corneas. The corneal epithelium of C57BL/6J mice was also evaluated to determine in vivo wound healing. An in vivo imaging system was also used to evaluate the effects of HA on eye drop retention on the ocular surface.Results: The findings revealed the promotion of HCE-T migration, in situ rabbit corneal epithelial migration, and in vivo wound healing in mouse corneal epithelium by HA. Pre-treatment with HA also protected against delayed epithelial wound healing in BAC in vitro. However, pre-treatment with 3 mg/mL HA did not show a protective effect against BAC in vivo, but instead delayed epithelial wound healing and increased detection of cleaved caspase-3. This suggested that HA promotes the retention of BAC on the ocular surface. The instilled HA was retained after 15 min, at a significantly higher rate than for phosphate-buffered saline.Conclusions: The combination of HA and BAC impaired wound healing in the corneal epithelium.

Optimization of the Interaction between Diclofenac and Ibuprofen with Benzalkonium Chloride to Prepare Ocular Nanosuspension.

BACKGROUND: Non-steroidal anti-inflammatory drugs are most commonly used in the management of ocular inflammations. These drugs have poorly aqueous solubility and weakly acidic nature. They interact with cationic quaternary ammonium compound benzalkonium chloride, used as a preservative in ophthalmic formulations, to form insoluble complexes. To overcome this incompatibility solubilizers like polysorbate 80, lysine salts, tocopheryl polyethylene glycol succinate etc. are used which are quite irritating and affect the corneal integrity. OBJECTIVE: The objective of the present study is to formulate nonirritating, compatible, microbiologically stable ophthalmic formulation with good corneal permeation characteristics. The interaction between diclofenac sodium or ibuprofen with benzalkonium chloride was optimized using a central composite experimental design to prepare nanosuspensions by nanoprecipitation. METHODS: The optimized batches of nanosuspensions were evaluated for ex vivo corneal permeation study, preservative challenge test and physical stability. The optimal concentrations of benzalkonium chloride for diclofenac sodium (0.1%, w/v) and ibuprofen (0.1% w/v) nanosuspensions were determined to be 0.002%(w/v), which had a respective average particle size of 440 nm and 331 nm, respectively. The nanosuspensions of diclofenac sodium and ibuprofen provided 1.6 and 2.1- fold higher ex vivo corneal permeation than their respective conventional aqueous solution dosage forms. Further, the concentration of benzalkonium chloride used in the formulations showed adequate preservative efficacy. RESULTS: The optimized nanosuspension formulations of diclofenac and ibuprofen were found to be physically stable and microbiologically safe with greater corneal penetration than the conventional solution dosage forms.

Nanoemulsion as an Effective Treatment against Human-Pathogenic Fungi.

Infections triggered by pathogenic fungi cause a serious threat to the public health care system. In particular, an increase of antifungal drug-resistant fungi has resulted in difficulty in treatment. A limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study, we demonstrate the efficacy of the nanoemulsion NB-201, which utilizes the surfactant benzalkonium chloride, against human-pathogenic fungi. We found that NB-201 exhibited in vitro activity against Candidaalbicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented an enhanced healing process after subcutaneous infections by multidrug-resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp., Aspergillus fumigatus, and Mucorales Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance developing, presenting a novel treatment to control fungal wound or skin infections.IMPORTANCE Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development.

Comparison of disinfection effect between benzalkonium chloride and povidone iodine in nasotracheal intubation: a randomized trial.

BACKGROUND: Nasotracheal intubation can potentially result in microbial contamination from the upper respiratory tract to the lower respiratory tracts. However, an ideal nasotracheal disinfection method is yet to be determined. Therefore, we compared the disinfection effects between benzalkonium chloride and povidone iodine in nasotracheal intubation. METHODS: Overall, this study enrolled 53 patients aged 20-70 years who were classified into classes 1 and 2 as per American Society of Anesthesiologists-physical status and were scheduled to undergo general anesthesia with NTI. Patients who did not give consent (n = 2) and who has an allergy for BZK or PVI were excluded from the study. The patients were randomly divided into two groups on the basis of the disinfection method: BZK (n = 26, one patient was discontinued intervention) and PVI (n = 25). 50 patients were assessed finally. The subjects' nasal cavities were swabbed both before (A) and after disinfection (B), and the internal surface of the endotracheal tube was swabbed after extubation (C). The swabs were cultured on Brain heart infusion agar and Mannitol salt agar. The number of bacteria per swab was determined and the rates of change in bacterial count (B/A, C/B) were calculated. The growth inhibitory activity of the disinfectants on Staphylococcus aureus were also investigated in vitro. RESULTS: Although the initial disinfection effects (B/A) were inferior for benzalkonium chloride compared with those for povidone iodine, the effects were sustained for benzalkonium chloride (C/B). In the in vitro growth inhibitory assay against S. aureus, benzalkonium chloride showed higher inhibitory activity than povidone iodine. CONCLUSION: Although both disinfectants were inactivated or diffused/diluted over time, benzalkonium chloride maintained the threshold concentration and displayed antimicrobial effects longer than povidone iodine; therefore, benzalkonium chloride appeared to show a better sustained effect. Benzalkonium chloride can be used for creating a hygienic nasotracheal intubation environment with sustained sterilizing effects. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000029645 ). Registered 21 Oct 2017.

Antileishmanial Activity of Niosomal Combination Forms of Tioxolone along with Benzoxonium Chloride against Leishmania tropica.

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 µg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.

Noninferiority of Preservative-free Versus BAK-preserved Latanoprost-timolol Fixed Combination Eye Drops in Patients With Open-angle Glaucoma or Ocular Hypertension.

PRéCIS:: Noninferiority of efficacy was demonstrated for a preservative-free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. PURPOSE: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprost-timolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. METHODS: Phase III, randomized, parallel-group, investigator-masked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preserved latanoprost-timolol fixed combination (15.7±2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservative-free alternative T2347 (N=127) or remain on the preserved comparator (N=115) for 84 days. Intraocular pressure changes from day 0 were measured at 9:00 am (±1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. RESULTS: The mean change in intraocular pressure from baseline to day 84 was -0.49±1.80 mm Hg for preservative-free T2347 and -0.49±2.25 mm Hg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P=0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P<0.001), and itching (P<0.01) on day 84. CONCLUSIONS: Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated.