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Background: Nasotracheal intubation (NTI) is necessary during surgeries requiring clear access to the surgical field and in patients with respiratory issues. This study investigates the pre-NTI nasal disinfection efficacy of different cotton swab sizes, hypothesizing that smaller swabs could minimize bleeding while maintaining disinfection efficacy. Methods: Patients classified as American Society of Anesthesiologists-physical status (ASA-PS) class 1 or 2 scheduled for general anesthesia with NTI were randomly assigned to either a large cotton swabs (LCS) or fine cotton swabs (FCS) group in this randomized controlled trial (RCT)." After anesthesia, a fine cotton swab was inserted into the inferior nasal meatus in both groups to collect bacteria (sample A). Next, the nasal cavity was disinfected with LCS or FCS according to the patient group. Bacteria were collected by inserting a fine cotton swab into the inferior nasal meatus (sample B). After surgery, bacteria were collected from the endotracheal tube tip using a fine cotton swab in both groups (sample C). The samples were cultured for 24 hours, and the colonies from samples A–C were counted. The changes in bacteria count between samples A and B and samples A and C were determined. Nasal bleeding from cotton swab insertion was assessed as a secondary outcome. Student's t-tests, a chi-square independence test, and Mann–Whitney U tests were used for the statistical analysis. The statistical significance level was set at p < 0.05. Results: Between samples A and B, the change in bacteria count was 7.2% (1.4–26.1%) (median[interquartile range]) in the LCS group and 6.9% (0.9–22%) in the FCS group (p = 0.90). Between samples A and C, the change in bacteria count was 7.5% (0.2–44%) in the LCS group and 8.3% (0.3–39%) in the FCS group (p = 0.55). We examined 62 subjects in each group (LCS and FCS), and samples A, B, and C were collected from all participants in both groups. Nasal bleeding occurred in 42/62 in the LCS group and 22/62 in the FCS group (p < 0.01). Conclusion: Cotton swab thickness did not impact disinfection efficacy, but large swabs increased the risk of nasal bleeding. We recommend FCS for nasal disinfection prior to NTI in ASA 1–2 patients, as they reduce bleeding risk without compromising disinfection. Trial registration: UMIN-CTR (registration no. UMIN000051495), June 30, 2023. [ABSTRACT FROM AUTHOR]

Purpose: Candida auris, a multidrug-resistant yeast, poses significant challenges in healthcare settings due to its ability to form biofilms and resistance to common disinfectants. Understanding its susceptibility to biocides used in hospital disinfection practices is crucial for infection control. We investigated the biocide sensitivity of eight clinical C. auris strains from different patients and one reference strain (CDC B11903) using the biocide activity tests. Methods: Species identification was confirmed through MALDI-TOF MS, while clade differentiation and phylogenetic classification were determined via whole-genome sequencing. Biofilm formation was assessed using the MTT assay. Antifungal susceptibilities were tested according to CLSI standards. The effectiveness of biocides, including chlorine, chlorhexidine, and benzalkonium chloride, was evaluated through broth microdilution following CLSI standards and quantitative suspension and carrier tests, following EN standards. Results: All clinical strains were identified as clade 1, and the reference strain as clade 4, with all exhibiting biofilm formation. Clade 1 strains showed resistance to fluconazole, with MIC values ranging from 8 to 32 µg/ml, while being susceptible to other antifungals. Broth microdilution MIC assays for biocides demonstrated that all strains exhibited resistance to benzalkonium chloride. Chlorine and chlorhexidine showed variable efficacy, dependent on concentration and environmental cleanliness. Alcohol-based hand sanitizers demonstrated effectiveness against C. auris from the first minute of application. Conclusion: The study highlights the variable susceptibility of C.auris to different biocides, underscoring the challenge in eradicating this pathogen from healthcare environments. Our findings advocate for the careful selection of disinfectants in hospital settings, emphasizing the need for high-concentration chlorine and chlorhexidine solutions to combat C. auris, even in especially clean environments. [ABSTRACT FROM AUTHOR]

Background/Objectives: Listeria monocytogenes is a foodborne pathogen that can infect both humans and animals and cause noninvasive gastrointestinal listeriosis or invasive listeriosis. The objectives of this study were to determine the genetic diversity of L. monocytogenes; the genes associated with its resistance to antibiotics, benzalkonium chloride (BC), and cadmium chloride (CdCl2); and its biofilm formation. Methods: A total of 132 fresh fruits (44 samples) and vegetables (88 samples) were selected for this study. The genetic diversity of the isolates and the genes associated with their antibiotic resistance were determined using PCR amplification; meanwhile, their levels of susceptibility to antibiotics were determined using the agar diffusion method. Their levels of resistance to BC and CdCl2 were determined using the minimum inhibitory concentration method, and their capacity for biofilm formation was evaluated using the crystal violet staining method. Results: A total of 17 L. monocytogenes strains were collected: 12.8% (17/132) from fresh fruits and vegetables in this study. The isolates of L. monocytogenes belonged to phylogenetic groups I.1 (29.4% (5/17); serotype 1/2a) and II.2 (70.5% (12/17); serotype 1/2b); strains containing Listeria pathogenicity islands (LIPIs) were also identified at prevalence rates of 100% for LIPI-1 and LIPI-2 (17/17), 29.4% for LIPI-3 (5/17), and 11.7% for LIPI-4 (2/17). The antibiotic susceptibility tests showed that the L. monocytogenes isolates exhibited six different multiresistant patterns, with multiple antibiotic resistance (MAR) index of ≥0.46 (70.5%; 12/17); additionally, the genes Ide, tetM, and msrA, associated with efflux pump Lde, tetracycline, and ciprofloxacin resistance, were detected at 52.9% (9/17), 29.4% (5/17), and 17.6% (3/17), respectively. The phenotypic tests showed that 58.8% (10/17) of cadmium-resistant L. monocytogenes isolates had a co-resistance of 23.5% (4/17) to BC. Finally, all strains of L. monocytogenes exhibited moderate biofilm production. Conclusions: The results of this study contribute to our understanding of the persistence and genetic diversity of L. monocytogenes strains isolated from fresh fruits and vegetables; in addition, their resistance to CdCl2, which is correlated with co-resistance to BC disinfectant, is helpful for the food industry. [ABSTRACT FROM AUTHOR]

Background: Linarine is a natural chemical component widely found in Buddleja officinalis Maxim., Chrysanthemum indicum L., Mentha canadensis L., and other medicinal plants. Modern pharmacological studies have shown that linarine with good anti-inflammatory and antioxidant activities can inhibit the proliferation and induce apoptosis of many kinds of tumor cells. Moreover, linarine showed protective effect on the liver, kidneys, and other organs. Methods: Inflammation model of human corneal epithelial cell (HCEC) was constructed using NaCl induction, and cytotoxicity was detected by the CCK8 assay. The levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were measured using Enzyme-linked immunoassay (ELISA). Chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops in a desiccator established a mouse model of dry eye disease (DED). The following parameters were recorded: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. The levels of inflammatory factors mitogen activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), c-Jun N-terminal kinase (JNK), IL-1β, Interleukin 18(IL-18), A2A, A3, P2X4, P2X7, P2Y1 were measured by using immunofluorescence (IF) staining. Results: Linarine can inhibit the secreation of TNF-α, and IL-1β in HCECs. Linarine prolonged tear film rupture time, promoted tear secretion, repaired corneal damage, and reduced the levels of inflammatory factors of MAPK, NF-kB, JNK, IL-1β, IL-18, and modulated the levels of the purinergic receptor. Conclusions: Linarine is effective in treating dry eye in mice by inhibiting purinergic receptors-mediated inflammatory response. [ABSTRACT FROM AUTHOR]

Three types of coatings (contact-based, release-based, and combined coatings with both contact-based and release-based actions) were prepared and tested for the ability to inactivate SARS-CoV-2. In these coatings, quaternary ammonium surfactants were used as active agents since quaternary ammonium compounds are some of the most commonly used disinfectants. To provide contact-based action, the glass and silicon surfaces with covalently attached quaternary ammonium cationic surfactant were prepared using a dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride modifier. Surface modification was confirmed by attenuated total reflection infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy, and contact angle measurements. The grafting density of the modifier was estimated by XPS and elemental analysis. To provide release-based action, the widely used quaternary ammonium cationic disinfectant, benzalkonium chloride (BAC), and a newly synthesized cationic gemini surfactant, C18-4-C18, were bound non-covalently to the surface either through hydrophobic or electrostatic interactions. Virus titration revealed that the surfaces with combined contact-based and release-based action and the surfaces with only release-based action completely inactivate SARS-CoV-2. Coatings containing only covalently bound disinfectant are much less effective; they only provide up to 1.25 log10 reduction in the virus titer, probably because of the low disinfectant content in the surface monolayer. No pronounced differences in the activity between the flat and structured surfaces were observed for any of the coatings under study. Comparative studies of free and electrostatically bound disinfectants show that binding to the surface of nanoparticles diminishes the activity. These data indicate that SARS-CoV-2 is more sensitive to the free disinfectants. [ABSTRACT FROM AUTHOR]

Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that Escherichia coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e., tolerance) and not by evolving the ability to grow at increased concentrations (i.e., resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 μg mL−1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two‐fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting for survival‐only led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at subinhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution. [ABSTRACT FROM AUTHOR]

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad® and SofZia®, demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS). [ABSTRACT FROM AUTHOR]

Biodeterioration is a significant problem in the conservation of stone heritage buildings. In this study, 10 plant essential oils were assessed for their effectiveness in biofilm inhibition on stone heritage building surfaces under laboratory and in situ conditions, and were compared with traditional biocides such as benzalkonium chloride. The plant extracts were tested against algae and mosses. The effect on algae removal was evaluated by measuring the color of the surface before treatment, after 24 h and after 1 month of treatment. The effect on mosses was assessed by measuring the photosynthetic pigment content of mosses after 24 h of treatment. The results showed that the different plant extracts exhibited different levels of antibiotic activity. Benzalkonium chloride, S. aromaticum and C. cassia extracts showed strong antibiotic activity against all algae and mosses tested. T. mongolicus extracts showed antibiotic activity against only some of the algae and mosses, while the application of P. cablin extracts increased chlorophyll b content in the mosses. The other plant extracts were less effective at inhibiting the growth of algae and mosses. GC–MS compositional analysis further indicated that the higher antibiotic activity of S. aromaticum and C. cassia extracts was related to the high content of eugenol and cinnamaldehyde. [ABSTRACT FROM AUTHOR]

Background/Objectives: The rise and spread of antimicrobial resistance complicates the treatment of bacterial wound pathogens, further increasing the need for newer, effective therapies. Azoles such as miconazole have shown promise as antibacterial compounds; however, they are currently only used as antifungals. Previous research has shown that combining azoles with quaternary ammonium compounds yields synergistic activity against fungal pathogens, but the effect on bacterial pathogens has not been studied yet. Methods: In this study, the focus was on finding active synergistic combinations of imidazoles and quaternary ammonium compounds against (multidrug-resistant) bacterial pathogens through checkerboard assays. Experimental evolution in liquid culture was used to evaluate the possible emergence of resistance against the most active synergistic combination. Results: Several promising synergistic combinations were identified against an array of Gram-positive pathogens: miconazole/domiphen bromide, ketoconazole/domiphen bromide, clotrimazole/domiphen bromide, fluconazole/domiphen bromide and miconazole/benzalkonium chloride. Especially, miconazole with domiphen bromide exhibits potential, as it has activity at a low concentration against a broad range of pathogens and shows an absence of strong resistance development over 11 cycles of evolution. Conclusions: This study provides valuable insight into the possible combinations of imidazoles and quaternary ammonium compounds that could be repurposed for (topical) wound treatment. Miconazole with domiphen bromide shows the highest application potential as a possible future wound therapy. However, further research is needed into the mode of action of these compounds and their efficacy and toxicity in vivo. [ABSTRACT FROM AUTHOR]

In this study, poly(lactic acid), poly(ethylene glycol), and benzalkonium chloride with different concentrations (3, 5, 7, and 9%wt.) (PLA/PEG/BCL) composite electrospun mats were produced. PLA is a non‐toxic polymer with high biocompatibility and biodegradability. However, it may be fragile due to its structure. Therefore, in this study, PEG was used as a plasticizer to improve the structural properties of PLA and it was aimed at providing antibacterial properties by adding BCL salt. Its use as an antibacterial composite nanomaterial effective against Gram‐positive Staphylococcus aureus (S. aureus) and Gram‐negative Escherichia coli (E. coli) bacterial cultures and as a dermal wound dressing material has been examined in two different areas. The addition of BCL salt reduced the bead formation in PLA/PEG nanofibers and increased the homogeneity of fiber dispersion. 9% BCL‐doped composite nanofiber was obtained as the smoothest and most homogeneous surface. This mat was reported to have the highest ductility. The low Tm of pure BCL salt enabled the Tg temperature of PLA/PEG/BCL composite nanofibers to be observed. It was observed that as the BCL salt ratio increased, the T5 and T10 temperatures of the nanofibers decreased and then increased. BCL‐doped mats exhibited liquid absorption behavior in the range of 497%–708%. PLA/PEG/BCL composite nanofibers showed high toxicity to the L929 fibroblast cell line. So, it has been reported that it cannot be used as a dermal wound dressing. PLA/PEG/BCL composite nanomaterials were reported to have 99.99% antibacterial activity against E. coli and S. aureus. It was suggested that it could be used in antibacterial coating applications by taking into account modern nanocoating technology. Highlights: Poly(lactic acid), poly(ethylene glycol), and benzalkonium chloride (PLA/PEG/BCL) composite electrospun mats were produced.The addition of BCL salt reduced the bead formation in PLA/PEG nanofibers and increased the homogeneity of fiber dispersion.9% BCL‐doped composite nanofiber was obtained as the smoothest and most homogeneous surface.PLA/PEG/BCL composite nanofibers showed high toxicity to the L929 fibroblast cell line.PLA/PEG/BCL composite nanomaterials were reported to have 99.99% antibacterial activity against E. coli and S. aureus. [ABSTRACT FROM AUTHOR]

Abstract Background Nasotracheal intubation (NTI) is necessary during surgeries requiring clear access to the surgical field and in patients with respiratory issues. This study investigates the pre-NTI nasal disinfection efficacy of different cotton swab sizes, hypothesizing that smaller swabs could minimize bleeding while maintaining disinfection efficacy. Methods Patients classified as American Society of Anesthesiologists-physical status (ASA-PS) class 1 or 2 scheduled for general anesthesia with NTI were randomly assigned to either a large cotton swabs (LCS) or fine cotton swabs (FCS) group in this randomized controlled trial (RCT).” After anesthesia, a fine cotton swab was inserted into the inferior nasal meatus in both groups to collect bacteria (sample A). Next, the nasal cavity was disinfected with LCS or FCS according to the patient group. Bacteria were collected by inserting a fine cotton swab into the inferior nasal meatus (sample B). After surgery, bacteria were collected from the endotracheal tube tip using a fine cotton swab in both groups (sample C). The samples were cultured for 24 hours, and the colonies from samples A–C were counted. The changes in bacteria count between samples A and B and samples A and C were determined. Nasal bleeding from cotton swab insertion was assessed as a secondary outcome. Student’s t-tests, a chi-square independence test, and Mann–Whitney U tests were used for the statistical analysis. The statistical significance level was set at p

Abstract Background Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). Methods This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension. Results Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. Conclusions Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. Trial registration The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

During the COVID-19 pandemic, the surge in disinfectant use emphasised their pivotal role in infection control. While the majority of antimicrobial resistance research focuses on antibiotics, resistance to biocides, which are present in disinfectants and sanitisers, is escalating. Serratia sp. HRI is a highly resistant isolate, and through the study of this organism, the molecular mechanisms of resistance may be uncovered. Serratia sp. HRI was treated with the disinfectant benzalkonium chloride in preparation for RNA sequencing. Through mining of the RNA-Seq differential expression data, an uncharacterised Major Facilitator Superfamily (MFS) efflux pump gene was found to be up-regulated at least four-fold at four different time points of exposure. Real-time PCR revealed this uncharacterised MFS efflux gene was up-regulated after exposure to benzalkonium chloride and two additional disinfectants, didecyldimethylammonium chloride (DDAC) and VirukillTM. Additionally, expression of this gene was found to be higher at 20 min versus 90 min of exposure, indicating that the up-regulation of this gene is an initial response to biocide treatment that decreases over time. This suggests that MFS efflux pumps may be an initial survival mechanism for microorganisms, allowing time for longer-term resistance mechanisms. This work puts forward a novel biocide resistance gene that could have a major impact on biocide susceptibility and resistance. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of disinfectant resistance has become a severe threat due to reduced effectiveness. This study was undertaken to determine how bacteria adapt to survive exposure to disinfectants in the busiest section of a tertiary care hospital in Varanasi, India. Methods: Four isolates (two Klebsiella pneumoniae, Kp1 and Kp2; two Pseudomonas aeruginosa, Pa1 and Pa2) were obtained from chlorhexidine (CHX)-based handwash during microbiological surveillance of "in-use disinfectants" in hospital. Six disinfectants [4% CHX, 2% glutaraldehyde, 7.5% hydrogen peroxide, 1% sodium hypochlorite and 0.1% benzalkonium chloride (BAC), and 70% ethyl alcohol] were tested against these four isolates to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Antibiotic profile, change in MIC on exposure to disinfectants and biofilm formation in the presence and absence of disinfectants was studied. Whole genome sequencing (WGS) was done to identify the resistance mechanisms. Result: The isolates showed the highest MBC/MIC ratio (4) against glutaraldehyde. Exposure to supra-inhibitory concentration of BAC for 21 days resulted in doubling of MIC/MBC. The majority (75%) of the isolates were multidrug resistant. All the isolates were strong biofilm producers. The reduction rate of biofilm formation decreased with an increase in the concentration of disinfectants (p = 0.05 for BAC). WGS revealed multiple AMR genes including blaDIM-1, disinfectant-resistant gene and efflux pump genes. Conclusion: The study emphasized the various adaptation strategies of these isolates for survival in disinfectant environment, thus posing a huge challenge for their control in the hospital environment. [ABSTRACT FROM AUTHOR]

(1) Background: L. monocytogenes is a food pathogen of great importance, characterized by a high mortality rate. Quaternary ammonium compounds (QACs), such as benzalkonium chloride (BC), are often used as disinfectants in food processing facilities. The effectiveness of disinfection procedures is crucial to food safety. (2) Methods: A collection of 153 isolates of L. monocytogenes from meat processing industry was analyzed for their sensitivity to BC using the agar diffusion method. Genes of interest were detected with PCR. (3) Results: Genes emrC, bcrABC, and qacH were found in 64 (41.8%), 6 (3.9%), and 1 isolate (0.7%), respectively, and 79 isolates (51.6%) were classified as having reduced sensitivity to BC. A strong correlation between carrying QACs resistance-related genes and phenotype was found (p-value < 0.0001). Among 51 isolates originating from bacon (collected over 13 months), 48 had the emrC gene, which could explain their persistent presence in a processing facility. Isolates with the ilsA gene (from LIPI-3) were significantly (p-value 0.006) less likely to carry QACs resistance-related genes. (4) Conclusions: Reduced sensitivity to QACs is common among L. monocytogenes from the meat processing industry. Persistent presence of these bacteria in a processing facility is presumably caused by emrC-induced QACs resistance. [ABSTRACT FROM AUTHOR]

Methane (CH4) dissolved in water is readily consumed by CH4‐oxidizing bacteria, so the possibility of the dissolved CH4 concentration (dCH4) in sampled water changing before analysis is a concern. To determine the accurate in situ dCH4 level, mercury chloride (HgCl2) or sodium azide (NaN3) is traditionally used for sample preservation. However, these preservatives are very toxic and great care must be taken when adding them to samples. Benzalkonium chloride (BAC), a quaternary ammonium salt cationic surfactant, is a readily available disinfectant that is less harmful to the human body than HgCl2, NaN3, and other preservatives. In this study, we investigated the usefulness of BAC in preserving dCH4 in swamp water, which is a critical terrestrial source of CH4. The dCH4 in samples without BAC decreased immediately after sample collection, whereas the dCH4 in the samples with added BAC did not change significantly for at least 15 d. In addition, when BAC was added to 18 water samples with different water chemistries, the dCH4 did not change significantly from immediately after sampling to 1 week after sampling (average difference: 3%). Thus, in the water samples used in this study, BAC effectively preserved dCH4 in the samples for at least 1 week. Further testing of the effect of BAC on the preservation of dCH4 in different types of water samples worldwide will help to establish a more complete, simple, and safe method. [ABSTRACT FROM AUTHOR]

Background: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). Methods: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension. Results: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. Conclusions: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. Trial registration: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39). [ABSTRACT FROM AUTHOR]

Listeria monocytogenes, a potentially fatal foodborne pathogen commonly found in food processing facilities, creates a significant economic burden that totals more than $2 billion annually in the United States due to outbreaks. Quaternary ammonium compounds (QACs), including benzalkonium chloride (BAC), are among the most widely used sanitizers to inhibit the growth and spread of L. monocytogenes from food processing facilities. However, resistance to QACs has been increasing in L. monocytogenes and different genetic mechanisms conferring resistance have been discovered. Here, we used ethyl methanesulfonate (EMS) to chemically mutagenize the BAC-susceptible strain, L. monocytogenes FSL-N1-304. We isolated two mutants with increased tolerance to BAC compared to the parental strain. Next, we assessed the off-target effect of increased tolerance to BAC by measuring the minimum inhibitory concentrations (MICs) of a diverse set of antibiotics, revealing that mut-1 and mut-2 displayed significantly increased resistance to fluoroquinolone antibiotics compared to the parental strain. A hemolysis assay was then used to investigate a potential correlation between BAC tolerance and virulence. Interestingly, mut-1 and mut-2 both exhibited significantly higher hemolysis percentage than the parental strain. We then sequenced the genomes of the parental strain and both mutants to identify mutations that may be involved in the increased resistance to BAC. We identified 3 and 29 mutations in mut-1 and mut-2, respectively. mut-1 contained nonsynonymous mutations in dagK (a diacylglycerol kinase), lmo2768 (a permease-encoding gene), and lmo0186 (resuscitation promoting factor). mut-2 contained a nonsense mutation in the nucleotide excision repair enzyme UvrABC system protein B encoding gene, uvrB, which likely accounts for the higher number of mutations observed. Transcriptome analysis in the presence of BAC revealed that genes related to the phosphotransferase system and internalins were up-regulated in both mutants, suggesting their significance in the BAC stress response. These two mutants provide insights into alternative mechanisms for increased BAC tolerance and could further our understanding of how L. monocytogenes persists in the food processing environment. [ABSTRACT FROM AUTHOR]

Background: Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in ophthalmology, can readily impact a dog's working capacity and lead to economic losses. Although there are several medications available for this disease, all of them only improve the symptoms on the surface of the eye, and they are irritating and not easy to use for long periods of time. Adipose-derived mesenchymal stem cells (ADMSC) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of ADMSC. Here, we aimed to use ADMSC overexpressing Secreted Protein Acidic and Rich in Cysteine (SPARC) to treat 0.25% benzalkonium chloride-treated dogs with dry eye to verify its efficacy. For in vitro validation, we induced corneal epithelial cell (HCECs) damage using 1 µg/mL benzalkonium chloride. Methods: Fifteen male crossbred dogs were randomly divided into five groups: normal, dry eye self-healing control, cyclosporine-treated, ADMSC-CMV-treated and ADMSC-OESPARC-treated. HCECs were divided into four groups: normal control group, untreated model group, ADMSC-CMV supernatant culture group and ADMSC-OESRARC supernatant culture group. Results: SPARC-modified ADMSC had the most significant effect on canine ocular surface inflammation, corneal injury, and tear recovery, and the addition of ADMSC-OESPARC cell supernatant also had a salvage effect on HCECs cellular damage, such as cell viability and cell proliferation ability. Moreover, analysis of the co-transcriptome sequencing data showed that SPARC could promote corneal epithelial cell repair by enhancing the in vitro viability, migration and proliferation and immunosuppression of ADMSC. Conclusion: The in vitro cell test and in vivo model totally suggest that the combination of SPARC and ADMSC has a promising future in novel dry eye therapy. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is capable of forming biofilms on the food contact surfaces, increasing the risk of food contamination by this pathogen. The disinfectant benzalkonium chloride (BC) is commonly used to control L. monocytogenes in the food industry. This study aimed to investigate effects of BC on L. monocytogenes biofilms. Biofilm biomass was measured by the microplate method with crystal violet staining. Results from the broth microdilution method showed that the minimum inhibitory concentration (MIC) of BC against L. monocytogenes 10403S was 8 µg·mL-1. Sub-MICs of BC inhibited the biofilm formation and lethal concentrations of BC removed mature biofilms of L. monocytogenes 10403S. The presence of BC reduced extracellular proteins and exopolysaccharides in biofilms. Additionally, upregulation of quorum sensing gene luxS and agrBDCA and downregulation of flagellum motility genes flaA, motA, and motB were observed in the presence of BC. The BC disinfectant has an excellent anti-biofilm activity against L. monocytogenes. [ABSTRACT FROM AUTHOR]

A novel chromogenic system for the liquid-liquid extraction and determination of trace amounts of tungsten(VI) was investigated. The system comprises 4-nitrocatechol (4NC) as a chromogenic reagent, sulfuric acid as a complexing medium, and benzalkonium chloride (BAC) as a source of bulky cations (BA+), which readily form chloroform-extractable ion-association complexes. The impact of foreign ions and reagents was studied, and the optimal conditions for the sensitive, selective, and inexpensive determination of tungsten(VI) were identified. The limit of detection, linear working range, and molar absorptivity at λmax (422 nm) were determined to be 31 ng cm-3, 0.1-4.4 µg cm-3, and 5.49 × 104 dm3 mol-1 cm-1, respectively. The composition of the extracted complex was 1:2:2 (W:4NC:BA). Two potential structures of its anionic component, [WO2(4NC)2]2-, were discussed based on optimizations at the B3LYP/CEP-4G theoretical level and comparison between theoretical and experimental spectra. [ABSTRACT FROM AUTHOR]

Gemini surfactants are dimeric molecules having two monomeric units connected by a spacer. Gemini surfactants, owing to their molecular structure have better surfactant properties than other monomeric surfactants. Esterquat class gemini surfactants can be synthesized using a spacer containing ester linkages. In the current study, the synthesis of novel esterquat gemini surfactants was carried out with spacers of varying chain lengths and was characterized using sophisticated instrumental methods. Various surfactant properties including foaming, emulsification, CMC, surface excess, antimicrobial activity and wetting potential using contact angle were analyzed and compared with benzalkonium chloride. It was observed that the CMC as low as 24.79 × 10−3 mM of the synthesized surfactants is potentially lower than that of conventional monomeric surfactants and was found to increase with an increase in spacer chain length. Further, the applicability and evaluation of performance properties of the synthesized surfactants were studied in fabric softener formulation. The water absorbency and whiteness retention of the formulation prepared using 12‐6‐12 GS was the highest due to its better wettability amongst other synthesized surfactants owing to its higher spacer chain length. To summarize, the surface and anti‐microbial properties of the synthesized surfactants vary greatly with the alteration in spacer chain length. [ABSTRACT FROM AUTHOR]

Chick performance and hatchability are adversely affected by microbial contamination of hatching eggs. Egg disinfection is therefore crucial to limiting bacterial numbers and optimizing production. The present study was applied to detect the effect of hatching eggs spraying (nest and floor) with two commercial disinfectants: A (H2O2, peracetic and acetic acid) and B (glutraldehyde and Benzalkonium chloride) on hatching parameters and eggshell microbial counts. Hatching eggs were collected from broiler breeder flocks at different ages (37, 47 and 57 weeks). The obtained results indicated that both disinfectants reduced the levels of bacteria in similar ways, but there were no significant differences between them. Concerning the hatching parameters; hatchability percentages (total and true) were lower than standard in both nest and floor eggs, and higher hatchability percentages were found in eggs sanitized with disinfectant A. However, the lowest values were reported in eggs of 57 weeks old breeders with both disinfectants. Conclusively, disinfectants A and B reduced the microbial load of hatching eggs of different ages, and some hatchability parameters were affected with flock age and the used disinfectants. [ABSTRACT FROM AUTHOR]

ABSTRACT Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that Escherichia coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e., tolerance) and not by evolving the ability to grow at increased concentrations (i.e., resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 μg mL−1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two‐fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting for survival‐only led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at subinhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution.

Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c, il-8, tir4 and inf-γ, but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC.

Background. Glaucoma as one of the most common eye diseases can be a comorbid condition of an epithelial corneal defect of various etiologies. Maintaining an optimal level of ophthalmotonus includes the prescription of antiglaucoma drugs, including benzalkonium chloride-preserved drugs.The aim of the study. To compare the effect of antiglaucoma drugs, as well as benzalkonium chloride (BC), on a primary culture of human corneal epithelium and A549 immortalized cell line.Methods. The effect of brimonidine, dorzolamide and timolol (1/100, 1/50, 1/20 and 1/10 dilutions; exposure 24 hours) on a monolayer of a human corneal epithelial primary culture and A549 immortalized cell line was assessed by structural changes in cells (phase-contrast microscopy) and MTT assay data. The cytotoxic effect of BC was studied in concentrations corresponding to its content in these dilutions of the antiglaucoma drug. Using a model of a linear defect in the monolayer of a corneal epithelial primary culture and A549 immortalized cell line, the effects of brimonidine, dorzolamide and timolol (1/100 and 1/20 dilutions; exposure 48 hours) were assessed by cell migration activity.Results. Among drugs (BC-free), dorzolamide (1/50, 1/20 and 1/10 dilutions) causes minor structural changes in human corneal epithelium and A549 immortalized cell line; timolol (1/100, 1/50, 1/20 and 1/10 dilutions) causes minor structural changes in A549 immortalized cell line. Structural changes in both types of cells, a decrease in their metabolic and migration activity occur under the influence of dorzolamide, brimonidine and timolol (BC-preserved) in 1/100, 1/50, 1/20 and 1/10 dilutions. BC at the studied concentrations exhibits a similar effect.Conclusion. The cytotoxic effect of antiglaucoma drugs is caused by the presence of BC in their composition. Despite similar morphofunctional changes in cells, A549 immortalized cell line is more resistant to the effects of drugs than the human corneal epithelial primary culture. When using it as a cellular model, it is advisable to change the experimental conditions (duration of exposure and concentration of the studied drug).

Unfortunately, the occurrence of various pathologies in the ENT organs still remains one of the pressing problems in global healthcare. The frequent manifestation of unwanted pathologies forces us to change methods, and sometimes to introduce something new into the medical care provided to patients. Researchers from the Center for Medical Statistics of the Scientific Research Institute of Medical Sciences and Medical Research, Moscow Health Department, having conducted a detailed analysis of the activities of otorhinolaryngological departments in medical organizations in the city of Moscow, found that in 2022 the number of all visits to otorhinolaryngologists exceeded 4.5 million, of which 45.7% were children, and 54.2% were committed by persons over 18 years of age. Preventive visits of patients to doctors for 2018–2022 increased from 29.3 to 37.8%. Infectious and inflammatory diseases of the oral cavity and pharynx are among the most common diseases of the ENT organs. Given the proliferation, development of technology and possible tensions, they still remain a pressing issue. That is why various new options for drug therapy are being proposed that would be most effective, and one of these new drugs is Lorothricin, a combination drug that has shown itself to be the best in a number of studies and clinical cases. In a review article, based on our experience and literature data. We present the problem of treating patients with sore throat due to acute pharyngitis, tonsillitis and gingivitis.

Abstract Background Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC), that can be found in a wide variety of household products–from disinfectants to medicaments and home fragrances–but also professional products. In pets, cats have long been reported as more sensitive than dogs to QACs; in fact, signs of irritation such as oral ulcerations, stomatitis and pharyngitis can be observed after contact with concentrations of 2% or lower. In a review of 245 cases of BAC exposure in cats, reported by the Veterinary Poisons Information Service (United Kingdom) only 1.2% of the cases died or were euthanized. Nevertheless, BAC toxidromes in cats can result in transitory CNS and respiratory distress, as well as severe mucosal and cutaneous lesions. Currently, only a few reports are available concerning BAC poisoning in this species. Case presentation A 4 month-old kitten presented with severe glossitis, lameness in the hindlimbs and episodes of vomiting and diarrhoea. The cause was unknown until the owners reported use of a BAC-containing mould remover (5%) 4 days later. The patient developed severe oral burns requiring a pharyngeal tube for feeding and severe cutaneous chemical burns. The kitten was managed with supportive therapy and required hospitalization for 10 days. The symptoms disappeared completely 3 weeks after exposure. Conclusions BAC is a very common compound contained in several household and professional products but, to the best of our knowledge, no previous case had been reported in Italy. We hope that this report will help raise awareness on the hazards of BAC products for cats in both domestic and work contexts.

Antimicrobial tolerance is a significant concern in the food industry, as it poses risks to food safety and public health. To overcome this challenge, synergistic combinations of antimicrobials have emerged as a potential solution. In this study, the combinations of two essential oil constituents (EOCs), namely carvacrol (CAR) and eugenol (EUG), with the quaternary ammonium compounds (QACs) benzalkonium chloride (BAC) and didecyldimethylammonium chloride (DDAC) were evaluated for their antimicrobial effects against Escherichia coli and Bacillus cereus, two common foodborne bacteria. The checkerboard assay was employed to determine the fractional inhibitory concentration index (FICI) and the fractional bactericidal concentration index (FBCI), indicating the presence of bactericidal, but not bacteriostatic, synergy in all QAC–EOC combinations. Bactericidal synergism was clearly supported by Bliss independence analysis. The bactericidal activity of the promising synergistic combinations was further validated by time–kill curves, achieving a >4-log10 reduction of initial bacterial load, which is significant compared to typical industry standards. The combinations containing DDAC showed the highest efficiency, resulting in the eradication of bacterial population in less than 2–4 h. These findings emphasize the importance of considering both bacteriostatic and bactericidal effects when evaluating antimicrobial combinations and the potential of EOC–QAC combinations for sanitization and disinfection in the food industry. [ABSTRACT FROM AUTHOR]

In this work, we demonstrate that a simple argentometric titration is a scalable, fast, green and robust approach for producing AgCl/antibiotic hybrid antimicrobial materials. We titrated AgNO3 into tetracycline hydrochloride (TCH) aqueous solution, thus forming AgCl/TCH in a one-step procedure. Furthermore, we investigated the one-pot synthesis of triply synergistic super-nanoantimicrobials, combining an inorganic source of Ag+ ions (AgCl), a disinfecting agent (benzyl-dimethyl-hexadecyl-ammonium chloride, BAC) and a molecular antibiotic (tetracycline hydrochloride, TCH). Conventional antimicrobial tests, industrial biofilm detection protocols, and in situ IR-ATR microbial biofilm monitoring, have been adapted to understand the performance of the synthesized super-nanoantimicrobial. The resulting hybrid AgCl/BAC/TCH nanoantimicrobials are found to be synergistically active in eradicating Salmonella enterica and Lentilactobacillus parabuchneri bacteria and biofilms. This study paves the way for the development of a new class of super-efficient nanoantimicrobials that combine relatively low amounts of multiple active species into a single (nano)formulation, thus preventing the development of antimicrobial resistance towards a single active principle. [ABSTRACT FROM AUTHOR]

Ocular surface staining for assessing corneal and conjunctival epithelium integrity is typically conducted using fluorescein, lissamine green, or rose Bengal dyes. Recently, a novel vital dye, REmark®, based on riboflavin, has been proposed for ocular surface examination. In the management of corneal and ocular surface diseases (OSD), the use of contact lenses is integral to therapeutic strategies. This study explores the compatibility of REmark® with four different types of disposable or bi-weekly soft contact lenses. Morphological variations observed under stereomicroscopy and ultraviolet (UV) ray transmittance in the visible spectrum (VIS) were evaluated at 2 and 4 h post-immersion of the contact lenses in both the original fluid and the new dye. The findings indicate no significant differences between the group treated with the original liquid and those immersed in REmark®, except for a yellow hue observed in the latter group, which dissipates after 8 h in physiological solution. This study highlights the potential of utilizing the new vital dye for ophthalmologic examinations even in the presence of applied soft contact lenses, offering a promising avenue for improved diagnostic practices and patient comfort. [ABSTRACT FROM AUTHOR]

Purpose: The effectiveness, safety and tolerability of the preservative-free fixed combination of tafluprost and timolol (PF-TTFC) were evaluated over the 24-h in patients with open-angle glaucoma or ocular hypertension showing signs and symptoms of Ocular Surface Disease (OSD) and uncontrolled intraocular pressure (IOP) on prior benzalkonium chloride (BAK) – Latanoprost monotherapy. Methods: In this multi-center, prospective, interventional, non-comparative clinical trial, patients treated with BAK-Latanoprost underwent 24-h IOP measurements (8 am, 11 am, 2 pm, 5 pm, 8 pm, 11 pm, 2 am, 5 am) at baseline and after 3 months from switch to PF-TTFC. Mean 24-h IOP and daytime (8 am– 8 pm) vs nighttime (11 pm – 5 am) IOP were compared. Changes in OSD signs and symptoms, quality of life (QoL) and in-vivo corneal confocal microscopy (IVCM) were also evaluated. Results: Thirty-eight patients were analyzed. The mean 24-h IOP significantly decreased after 3 months from 17.8 mmHg (95% CI: 17.1– 18.6) to 15.3 mmHg (95% CI: 14.6– 16.1, p < 0.001). IOP was significantly reduced both at daytime (p < 0.001) and nighttime (p < 0.001), with better IOP control at night [− 2.9 (95% CI: − 3.5 to − 2.1) mmHg vs − 2.3 (95% CI: − 2.9 to − 1.6) mmHg]. In 20 patients (52.6%), corneal fluorescein staining improved, whereas in 4 patients (10.5%) it worsened. Hyperemia has improved in 24 (63.3%) patients and worsened in 2 (5.3%). Breakup time, Schirmer test and QoL scores showed no changes. At IVCM, the mean corneal wing-cell size was found significantly decreased (p < 0.005). Conclusion: The switch from BAK-Latanoprost to PF-TTFC significantly reduced IOP over the 24-h and improved OSD signs and symptoms. [ABSTRACT FROM AUTHOR]

Bacterial infection is a major threat to public health. Nanotechnology offers a solution by combining nanomaterials with antibacterial agents. The development of an effective nanocomposite against drug‐resistant bacteria such as methicillin‐resistant Staphylococcus aureus (MRSA) is highly important yet challenging. Here, an anti‐MRSA core–shell structure is designed, containing antibacterial zeolitic imidazolate framework‐8 (ZIF‐8) as the core and bactericidal benzalkonium chloride (BAC) templated rough‐surface mesostructured silica nanocomposite (RMSN) as the shell. The resultant ZIF‐8@RMSN nanocomposite exhibits sustained release of BAC and zinc ions, effective disruption of the bacterial membrane, generation of oxidative damage of bacterial DNA, leakage of intracellular components, and finally bacterial death. Furthermore, the synergistic antibacterial mechanisms lead to enhanced biofilm elimination performance. In addition, the ZIF‐8@RMSN‐modified band‐aid effectively combats MRSA infection in vivo. This work has provided a promising nanocomposite against MRSA‐related infections. [ABSTRACT FROM AUTHOR]

Objective: This review aims to assess the efficacy of various materials and systems, including Chlorhexidine Digluconate, Benzalkonium Chloride, Hydrogen Peroxide, Sodium Hypochlorite, Iodine, Aloe Vera, Hyaluronic Acid, Propolis, Ozone, Photoactivated Disinfection, Lasers, and Antibacterial Dentin Adhesives, in cavity disinfection. Methods: A comprehensive review of literature and studies was conducted to evaluate the effectiveness of the mentioned materials and systems for cavity disinfection. Results: The review revealed diverse effects of Chlorhexidine Digluconate, Benzalkonium Chloride, Hydrogen Peroxide, Sodium Hypochlorite, Iodine, Aloe Vera, Hyaluronic Acid, Propolis, Ozone, Photoactivated Disinfection, Lasers, and Antibacterial Dentin Adhesives on cavity disinfection. The findings highlight the potential of these agents and technologies in enhancing disinfection protocols in dental practice. Conclusion: This review underscores the importance of exploring various materials and systems for cavity disinfection to improve dental treatment outcomes. Further research and clinical trials are warranted to validate the efficacy and safety of these agents and technologies in dental settings. [ABSTRACT FROM AUTHOR]

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC), that can be found in a wide variety of household products–from disinfectants to medicaments and home fragrances–but also professional products. In pets, cats have long been reported as more sensitive than dogs to QACs; in fact, signs of irritation such as oral ulcerations, stomatitis and pharyngitis can be observed after contact with concentrations of 2% or lower. In a review of 245 cases of BAC exposure in cats, reported by the Veterinary Poisons Information Service (United Kingdom) only 1.2% of the cases died or were euthanized. Nevertheless, BAC toxidromes in cats can result in transitory CNS and respiratory distress, as well as severe mucosal and cutaneous lesions. Currently, only a few reports are available concerning BAC poisoning in this species. Case presentation: A 4 month-old kitten presented with severe glossitis, lameness in the hindlimbs and episodes of vomiting and diarrhoea. The cause was unknown until the owners reported use of a BAC-containing mould remover (5%) 4 days later. The patient developed severe oral burns requiring a pharyngeal tube for feeding and severe cutaneous chemical burns. The kitten was managed with supportive therapy and required hospitalization for 10 days. The symptoms disappeared completely 3 weeks after exposure. Conclusions: BAC is a very common compound contained in several household and professional products but, to the best of our knowledge, no previous case had been reported in Italy. We hope that this report will help raise awareness on the hazards of BAC products for cats in both domestic and work contexts. [ABSTRACT FROM AUTHOR]

Aims: The exploration of new strategies for effective microbial control is one of the most significant studies in developing new formulations of antimicrobial agents. The increasing prevalence of microbial threats is a pressing threat to public health. Hence, this study aims to investigate the synergies between combinations of polyhexamethylene biguanide (PHMB) and benzalkonium chloride (BKC) compared to the individual PHMB or BKC as active agents for microbial control. A set of combinations of the active ingredient was tested against two Gram-positive bacteria, Bacillus cereus and Staphylococcus aureus, and two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa. Methodology and results: The antibacterial activity of PHMB and BKC was investigated using the microdilution method to determine their minimum inhibitory concentrations (MIC). The results showed that PHMB was more effective against Gram-positive bacteria, with a significant effect on B. cereus with a MIC value of 31.25 ppm, while having a lesser impact on E. coli (125 ppm). The MIC value of BKC was 15.625 ppm for the Gram-positive bacteria and showed a more prominent effect on Gram-negative bacteria. The MIC values were used as the baseline for formulating PHMB and BKC mixtures. The formulated combinations were evaluated using disc diffusion (DD) and well diffusion (WD) methods. The results indicated that the combined active agents have an efficiency similar to the stand-alone effect. The cytotoxic effect of these compounds was also assessed, and they showed toxic traits towards Vero cells, indicating that these two cationic agents acted additively towards each other. Conclusion, significance and impact of study: The combination of PHMB and BKC represented a potential strategy of mixed antimicrobial agents, which could be applied in applications such as healthcare and consumer products. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Glass ionomer cements (GICs), the most frequently used restorative materials in pediatric dentistry, may be used as medium for slow release of other active anti-microbial components apart from fluoride. OBJECTIVES: The objectives of this study were to determine the level of released chloride ions and anti-microbial compounds by incorporating 2% anti-microbial agents into conventional and experimental GICs. MATERIAL AND METHODS: The study was carried out using a conventional glass ionomer cements ChemFlex and Fuji IX as well as experimental glass ionomer cement MP4 and anti-microbial compounds, such as cetylpyridinium chloride and benzalkonium chloride. A total of 36 specimens (4 mm x 6 mm) were prepared, including 6 specimens of each GIC integrated with 2% of anti-microbial agents, and other six samples of the same cement without any anti-microbial agents used as a control group. Amounts of released Cl-- ions were determined with the use of an ion-selective electrode, and amounts of anti-microbial agents were determined by UV/VIS spectrophotometer. Measurements were performed at 9 successive time intervals starting from fifteenth minute and finishing after seven days. RESULTS: The results obtained show a continual release of both chloride ions and anti-microbial compounds from analyzed GICs that increased over time. CONCLUSIONS: In comparison with conventional GICs, MP4 GIC produces a significantly higher release both of chloride ions and anti-microbial compounds. [ABSTRACT FROM AUTHOR]

The role of biocides in the spread of antimicrobial resistance (AMR) has been addressed but only a few studies focus on the impact of surfactants on microbial diversity and AMR, although they are common constituents of cleaners, disinfectants, and personal care products and are thus released into the environment in large quantities. In this study, we used a static ex situ biofilm model to examine the development of four biofilms exposed to surfactants and analyzed the biofilms for their prevalence of class I integrons as a proxy for the overall abundance of AMR in a sample. We furthermore determined the shift in bacterial community composition by high-resolution melt analysis and 16S ribosomal RNA (16S rRNA) gene sequencing. Depending on the initial intrinsic prevalence of class I integrons in the respective ex situ biofilm, benzalkonium chloride, alkylbenzene sulfonate, and cocamidopropyl betaine increased its prevalence by up to 6.5× on average. For fatty alcohol ethoxylate and the biosurfactants sophorolipid and rhamnolipid, the mean increase did not exceed 2.5-fold. Across all surfactants, the increase in class I integrons was accompanied by a shift in bacterial community composition. Especially benzalkonium chloride, cocamidopropyl betaine, and alkylbenzene sulfonate changed the communities, while fatty alcohol ethoxylate, sophorolipid, and rhamnolipid had a lower effect on the bacterial biofilm composition. [ABSTRACT FROM AUTHOR]

IntroductionThe emergence of disinfectant resistance has become a severe threat due to reduced effectiveness. This study was undertaken to determine how bacteria adapt to survive exposure to disinfectants in the busiest section of a tertiary care hospital in Varanasi, India.MethodsFour isolates (two Klebsiella pneumoniae, Kp1 and Kp2; two Pseudomonas aeruginosa, Pa1 and Pa2) were obtained from chlorhexidine (CHX)–based handwash during microbiological surveillance of “in-use disinfectants” in hospital. Six disinfectants [4% CHX, 2% glutaraldehyde, 7.5% hydrogen peroxide, 1% sodium hypochlorite and 0.1% benzalkonium chloride (BAC), and 70% ethyl alcohol] were tested against these four isolates to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Antibiotic profile, change in MIC on exposure to disinfectants and biofilm formation in the presence and absence of disinfectants was studied. Whole genome sequencing (WGS) was done to identify the resistance mechanisms.ResultThe isolates showed the highest MBC/MIC ratio (4) against glutaraldehyde. Exposure to supra-inhibitory concentration of BAC for 21 days resulted in doubling of MIC/MBC. The majority (75%) of the isolates were multidrug resistant. All the isolates were strong biofilm producers. The reduction rate of biofilm formation decreased with an increase in the concentration of disinfectants (p = 0.05 for BAC). WGS revealed multiple AMR genes including blaDIM-1, disinfectant-resistant gene and efflux pump genes.ConclusionThe study emphasized the various adaptation strategies of these isolates for survival in disinfectant environment, thus posing a huge challenge for their control in the hospital environment.

Objective: To study peculiarities of skin wound healing under ischemic conditions with topical treatment using a combination of benzalkonium chloride and dexpanthenol.Materials and methods: We conducted an experiment on a rat model of skin wound healing under ischemic conditions. Male Wistar rats were divided into 4 groups, with 30 rats in each group. Group 1 received no treatment; group 2 was treated with the Levomecol ointment; group 3 and group 4 were treated with benzalkonium chloride immobilized based on the carboxymethylcellulose sodium salt and a combination of benzalkonium chloride and dexpanthenol immobilized based on the carboxymethylcellulose sodium salt, respectively. We used planimetric and biochemical (alkaline phosphatase [ALP] level) methods, measured the pH of the wound surface and wound bed temperature, determined the hydroxyproline concentration in the wound defect tissues, and performed statistical processing of the data.Results: Group 4 had the largest percentage of wound surface area reduction and pH values. Thermometry on day 10 showed a decrease in wound temperature in groups 2 and 4, whereas groups 1 and 3 demonstrated maximum values. By the end of the experiment, group 4 had the maximum hydroxyproline concentration that was significantly higher than the amino acid content in groups 1, 2, and 3: 1.2, 1.1 and 1.1 times higher, respectively. Maximum ALP levels were observed on day 5 in group 4, whereas in groups 2 and 3 they were observed on day 8 and only on day 10 in group 1.Conclusions: Skin wound healing under ischemic conditions was faster in the group in which topical treatment involved a combination developed by us: benzalkonium chloride and dexpanthenol immobilized based on the carboxymethylcellulose sodium salt.

Background/Objectives: Listeria monocytogenes is a foodborne pathogen that can infect both humans and animals and cause noninvasive gastrointestinal listeriosis or invasive listeriosis. The objectives of this study were to determine the genetic diversity of L. monocytogenes; the genes associated with its resistance to antibiotics, benzalkonium chloride (BC), and cadmium chloride (CdCl2); and its biofilm formation. Methods: A total of 132 fresh fruits (44 samples) and vegetables (88 samples) were selected for this study. The genetic diversity of the isolates and the genes associated with their antibiotic resistance were determined using PCR amplification; meanwhile, their levels of susceptibility to antibiotics were determined using the agar diffusion method. Their levels of resistance to BC and CdCl2 were determined using the minimum inhibitory concentration method, and their capacity for biofilm formation was evaluated using the crystal violet staining method. Results: A total of 17 L. monocytogenes strains were collected: 12.8% (17/132) from fresh fruits and vegetables in this study. The isolates of L. monocytogenes belonged to phylogenetic groups I.1 (29.4% (5/17); serotype 1/2a) and II.2 (70.5% (12/17); serotype 1/2b); strains containing Listeria pathogenicity islands (LIPIs) were also identified at prevalence rates of 100% for LIPI-1 and LIPI-2 (17/17), 29.4% for LIPI-3 (5/17), and 11.7% for LIPI-4 (2/17). The antibiotic susceptibility tests showed that the L. monocytogenes isolates exhibited six different multiresistant patterns, with multiple antibiotic resistance (MAR) index of ≥0.46 (70.5%; 12/17); additionally, the genes Ide, tetM, and msrA, associated with efflux pump Lde, tetracycline, and ciprofloxacin resistance, were detected at 52.9% (9/17), 29.4% (5/17), and 17.6% (3/17), respectively. The phenotypic tests showed that 58.8% (10/17) of cadmium-resistant L. monocytogenes isolates had a co-resistance of 23.5% (4/17) to BC. Finally, all strains of L. monocytogenes exhibited moderate biofilm production. Conclusions: The results of this study contribute to our understanding of the persistence and genetic diversity of L. monocytogenes strains isolated from fresh fruits and vegetables; in addition, their resistance to CdCl2, which is correlated with co-resistance to BC disinfectant, is helpful for the food industry.

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad® and SofZia®, demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS).

The rapid increase in the antibiotic resistance of microorganisms, capable of causing diseases in humans as destroying cultural heritage sites, is a great challenge for modern science. In this regard, it is necessary to develop fundamentally novel and highly active compounds. In this study, a series of N4-alkylcytidines, including 5- and 6-methylcytidine derivatives, with extended alkyl substituents, were obtained in order to develop a new generation of antibacterial and antifungal biocides based on nucleoside derivatives. It has been shown that N4-alkyl 5- or 6-methylcytidines effectively inhibit the growth of molds, isolated from the paintings in the halls of the Ancient Russian Paintings of the State Tretyakov Gallery, Russia, Moscow. The novel compounds showed activity similar to antiseptics commonly used to protect works of art, such as benzalkonium chloride, to which a number of microorganisms have acquired resistance. It was also shown that the activity of N4-alkylcytidines is comparable to that of some antibiotics used in medicine to fight Gram-positive bacteria, including resistant strains of Staphylococcus aureus and Mycobacterium smegmatis. N4-dodecyl-5- and 6-methylcytidines turned out to be the best. This compound seems promising for expanding the palette of antiseptics used in painting, since quite often the destruction of painting materials is caused by joint fungi and bacteria infection. [ABSTRACT FROM AUTHOR]

Contamination caused by fungi stands out as a significant microbiological issue in the food industry, particularly leading to premature spoilage across various food segments, including the dry-fermented meat industry. The emergence of undesired fungi on product surfaces results in substantial economic losses. Once microorganisms infiltrate the food, contamination ensues, and their subsequent proliferation can adversely impact the product's appearance, odor, flavor, and texture. This, in turn, leads to consumer rejection and negatively affects the commercial brand. Additionally, concerns persist regarding the potential presence of mycotoxins in these products. Given the detrimental effects of spoilage fungi in the food industry, practices such as thorough cleaning and sanitization become crucial to prevent contamination and subsequent premature deterioration. These measures play a pivotal role in ensuring the quality and safety of food, while also extending the shelf life of products. This review delves into the advantages, disadvantages, and factors that may influence the efficacy of commonly used sanitizers in the dry-fermented cured meat industry, including substances like sodium hypochlorite, peracetic acid, and benzalkonium chloride. [ABSTRACT FROM AUTHOR]

Campylobacter spp. are significant zoonotic agents, which cause annually millions of human cases of foodborne gastroenteritis worldwide. Their inclusion in biofilms on abiotic surfaces seems to play a pivotal role in their survival outside of the host, growth, and spread. To successfully mitigate the risks that arise with these bacteria, it is crucial to decrease their prevalence within the food production chain (from farm to the table), alongside the successful treatment of the resulting illness, known as campylobacteriosis. For this, the use of various antimicrobial agents remains actively in the foreground. A general-purpose biocide and cationic surfactant (benzalkonium chloride; BAC), a widely used macrolide antibiotic (erythromycin; ERY), and a naturally occurring organic acid (L(+)-lactic acid; LA) were comparatively evaluated in this work for their potential to inhibit both the planktonic and biofilm growth of 12 selected Campylobacter spp. (of which, seven were C. jejuni and five were C. coli) raw chicken meat isolates, all grown in vitro as monocultures. The inhibitory action of LA was also studied against four mixed-culture Campylobacter biofilms (each composed of three different isolates). The results showed that the individual effectiveness of the agents varied significantly depending on the isolate, growth mode (planktonic, biofilm), intercellular interactions (monocultures, mixed cultures), and the growth medium used (with special focus on blood presence). Thus, BAC exhibited minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) that ranged from 0.5 to 16 μg/mL. Interestingly enough, these values varied widely from 0.25 to 1024 μg/mL for ERY. Concerning LA, the MICs, MBCs, and MBICs varied from 1024 to 4096 μg/mL, with mixed-culture biofilm formation always being more difficult to suppress when compared to biofilm monocultures. In addition, it was evident that intercellular interactions encountered within mixed-culture Campylobacter biofilms significantly influenced both the population dynamics and the tolerance of each consortium member to acid exposure. Overall, the findings of this study provide useful information on the comparative effectiveness of three well-known antimicrobial agents for the control of Campylobacter spp. under various growth modes (i.e., planktonic, biofilm, monocultures, mixed cultures) that could potentially be encountered in food production and clinical settings. [ABSTRACT FROM AUTHOR]

Vibrio spp. are opportunistic human and animal pathogens found ubiquitously in marine environments. Globally, there is a predicted rise in the prevalence of Vibrio spp. due to increasing ocean temperatures, which carries significant implications for public health and the seafood industry. Consequently, there is an urgent need for enhanced strategies to control Vibrio spp. and prevent contamination, particularly in aquaculture and seafood processing facilities. Presently, these industries employ various disinfectants, including benzalkonium chloride (BAC), as part of their management strategies. While higher concentrations of BAC may be effective against these pathogens, inadequate rinsing post-disinfection could result in residual concentrations of BAC in the surrounding environment. This study aimed to investigate the adaptation and survival of Vibrio spp. exposed to varying concentrations of BAC residues. Results revealed that Vibrio bacteria, when exposed, exhibited a phenotypic adaptation characterized by an increase in biofilm biomass. Importantly, this effect was found to be strainspecific rather than species-specific. Exposure to BAC residues induced physiological changes in Vibrio biofilms, leading to an increase in the number of injured and alive cells within the biofilm. The exact nature of the "injured" bacteria remains unclear, but it is postulated that BAC might heighten the risk of viable but non-culturable (VBNC) bacteria development. These VBNC bacteria pose a significant threat, especially since they cannot be detected using the standard culture-based methods commonly employed for microbiological risk assessment in aquaculture and seafood industries. The undetected presence of VBNC bacteria could result in recurrent contamination events and subsequent disease outbreaks. This study provides evidence regarding the role of c-di-GMP signaling pathways in Vibrio adaptation mechanisms and suggests that c-di-GMP mediated repression is a potential avenue for further research. The findings underscore that the misuse and overuse of BAC may increase the risk of biofilm development and bacterial survival within the seafood processing chain. [ABSTRACT FROM AUTHOR]

Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions. [ABSTRACT FROM AUTHOR]

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate. [ABSTRACT FROM AUTHOR]