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Proper protection of vascular access after haemodialysis is one of the key measures for the prevention of catheter-related infections. Various substances with bactericidal and anticoagulant properties are used to fill catheters, but due to the unsatisfactory clinical effects and occurrence of adverse reactions, the search for new substances is still ongoing. In the present paper, we compared the in vitro antimicrobial activity of solutions used for tunnelled catheter locking (taurolidine, trisodium citrate) and solutions of substances that could potentially be used for this purpose (sodium bicarbonate, polyhexanide-betaine). The studies have been conducted on bacteria that most commonly cause catheter-related infections. The values of both minimum inhibitory concentration and minimum biofilm eradication concentration of the substances were determined. The ability of the tested substances to eradicate biofilm from the dialysis catheter surface was also evaluated. The results showed that polyhexanide-betaine inhibited the growth of all microbes comparably to taurolidine, even after ≥ 32-fold dilution. The activity of trisodium citrate and sodium bicarbonate was significantly lower. Polyhexanide exhibited the highest activity in the eradication of bacterial biofilm on polystyrene plates. The biofilm formed on a polyurethane dialysis catheter was resistant to complete eradication by the test substances. Polyhexanide-betaine and taurolidine showed the highest activity. Inhibition of bacterial growth regardless of species was observed not only at the highest concentration of these compounds but also after dilution 32–128x (taurolidine) and 32–1024x (polyhexanide-betaine). Therefore, it can be assumed that taurolidine application as a locking solution prevents catheter colonization and systemic infection development. Taurolidine displays high antimicrobial efficacy against Gram-positive cocci as well as Gram-negative bacilli. On the contrary, the lowest antibacterial effect displayed product contained sodium bicarbonate. The inhibitions of bacterial growth were not satisfactory to consider it as a substance for colonization prevention. Polyhexanidine-betaine possessed potent inhibitory and biofilm eradication properties comparing to all tested products. PHMB is applied as a wound irrigation solution worldwide. However, based on our results, we assume that the PHMB is a promising substance for catheter locking solutions thanks to its safety and high antimicrobial properties. [ABSTRACT FROM AUTHOR]

Objective: To quantify the bacterial burden after skin disinfection using an alcohol octenidine dihydrochloride combination (Octenisept®) compared to an 74.1% ethanol 10% 2-propanol combination (Softasept N®). Study design: Prospective randomized clinical trial. Material & methods: 61 dogs undergoing clean or clean-contaminated surgeries (excluding surgeries on the gastrointestinal tract) were randomly assigned to group O (skin disinfection with alcohol and octenidine dihydrochloride after washing with octenidine containing soap) or to control group C (skin disinfection using the ethanol-2-propanol combination after washing with a neutral soap without antiseptic ingredients). Samples were then taken from 8 different locations within the surgical field at four different stages: after clipping, after washing, after disinfection and one hour later. At each stage, two different sampling techniques (wet-dry swab technique (WDS) and contact plates (CP)) were used for quantitative analysis of bacterial counts. Results: WDS detected about 100-fold more bacteria compared to CP sampling in cases with high bacterial burden, but was not accurate enough to detect small numbers. CP sampling was therefore used for comparison of treatment protocols. 30 dogs were assigned to group O and 31 to group C. A relative reduction of 69% in group O and 77 percent in group C was observed after the soap wash. No significant differences were detected between both groups. Washing and disinfection resulted in a reduction of bacterial counts of 99.99% in group O versus 99.7% in group C (p = 0.018). Bacterial reduction one hour after washing and disinfection was significantly higher in group O (99.9%) than in group C (98.5%, p = 0.001). Conclusion: Additional octenidine dihydrochloride provided a slightly better decontamination effect after disinfection, particularly one hour after, which means it may only be indicated in longer surgeries. WDS is more sensitive but less specific to detect bacteria on the skin than the CP sampling. [ABSTRACT FROM AUTHOR]

Background: Over 10% of maternal deaths annually are due to sepsis. Prophylactic antibiotics and antiseptic agents are critical interventions to prevent maternal peripartum infections. We conducted a mixed-method systematic review to better understand factors affecting the use of prophylactic antibiotics and antiseptic agents to prevent peripartum infections. Methods: We searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health, Global Index Medicus, and Maternity and Infant Care for studies published between 1 January 1990 and 27 May 2022. We included primary qualitative, quantitative, and mixed-methods studies that focused on women, families, and healthcare providers' perceptions and experiences of prophylactic antibiotic and antiseptics during labour and birth in health facilities. There were no language restrictions. We used a thematic synthesis approach for qualitative evidence and GRADE-CERQual approach for assessing confidence in these review findings. Quantitative study results were mapped to the qualitative findings and reported narratively. Results: We included 19 studies (5 qualitative, 12 quantitative and 2 mixed-methods studies), 16 relating to antibiotics, 2 to antiseptic use, and 1 study to both antibiotic and antiseptic use. Most related to providers' perspectives and were conducted in high-income countries. Key themes on factors affecting antibiotic use were providers' beliefs about benefits and harms, perceptions of women's risk of infection, regimen preferences and clinical decision-making processes. Studies on antiseptic use explored women's perceptions of vaginal cleansing, and provider's beliefs about benefits and the usefulness of guidelines. Conclusion: We identified a range of factors affecting how providers use prophylactic antibiotics at birth, which can undermine implementation of clinical guidelines. There were insufficient data for low-resource settings, women's perspectives, and regarding use of antiseptics, highlighting the need for further research in these areas. Implications for practice include that interventions to improve prophylactic antibiotic use should take account of local environments and perceived infection risk and ensure contextually relevant guidance. [ABSTRACT FROM AUTHOR]

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs. [ABSTRACT FROM AUTHOR]

Introduction: Presoaking meshes for hernia repair with antiseptics prior to implantation could decrease the adhesion of microorganisms to the material surface and reduce the risk of antibiotic resistances. In this work, we evaluate chlorhexidine and allicin (natural antiseptic not yet tested for these purposes) against vancomycin as antiseptics to be used in the pretreatment of a heavyweight polypropylene mesh using an in vitro model of bacterial contamination. Methods: Solutions of saline, vancomycin (40 µg/mL), allicin (1,000 µg/mL), chlorhexidine (2%-0.05%) and the combination allicin-chlorhexidine (900 µg/mL-0.05%) were analyzed with agar diffusion tests in the presence of 106 CFU Staphylococcus aureus ATCC25923. Additionally, sterile fragments of Surgipro (1 cm2) were soaked with the solutions and cultured onto contaminated agar plates for 24/48/72 h. The antimicrobial material DualMesh Plus was utilized as positive control. At every time, the inhibition zones were measured and the bacterial adhesion to the mesh surface quantified (sonication, scanning electron microscopy). Cytotoxicity of the treatments was examined (alamarBlue) using rabbit skin fibroblasts. Results: The largest zones of inhibition were created by allicin-chlorhexidine. Chlorhexidine was more effective than vancomycin, and allicin lost its effectiveness after 24 h. No bacteria adhered to the surface of the DualMesh Plus or the meshes soaked with vancomycin, chlorhexidine and allicin-chlorhexidine. On the contrary, saline and allicin allowed adherence of high loads of bacteria. Vancomycin had no toxic effects on fibroblasts, while allicin and chlorhexidine exerted high toxicity. Cytotoxicity was significantly reduced with the allicin-chlorhexidine combination. Conclusions: The use of antiseptics such as chlorhexidine, alone or combined with others like allicin, could represent an adequate prophylactic strategy to be used for hernia repair materials because soaking with these agents provides the mesh with similar antibacterial properties to those observed after soaking with vancomycin, similar to the effect of DualMesh Plus. [ABSTRACT FROM AUTHOR]

‘Onium’ compounds, including ammonium and phosphonium salts, have been employed as antiseptics and disinfectants. These cationic biocides have been incorporated into multiple materials, principally to avoid bacterial attachment. In this work, we selected 20 alkyl-triphenylphosphonium salts, differing mainly in the length and functionalization of their alkyl chains, in fulfilment of two main objectives: 1) to provide a comprehensive evaluation of the antifouling profile of these molecules with relevant marine fouling organisms; and 2) to shed new light on their potential applications, beyond their classic use as broad-spectrum biocides. In this regard, we demonstrate for the first time that these compounds are also able to act as non-toxic quorum sensing disruptors in two different bacterial models (Chromobacterium violaceum and Vibrio harveyi) as well as repellents in the mussel Mytilus galloprovincialis. In addition, their inhibitory activity on a fouling-relevant enzymatic model (tyrosinase) is characterized. An analysis of the structure-activity relationships of these compounds for antifouling purposes is provided, which may result useful in the design of targeted antifouling solutions with these molecules. Altogether, the findings reported herein provide a different perspective on the biological activities of phosphonium compounds that is particularly focused on, but, as the reader will realize, is not limited to their use as antifouling agents. [ABSTRACT FROM AUTHOR]

Background: Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence. Methods: We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors9 attribution. Results: In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8-35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines. Conclusions: Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety. [ABSTRACT FROM AUTHOR]

Background: In order to fight the spread of the novel H1N1 influenza, health authorities worldwide called for a change in hygiene behavior. Within a longitudinal study, we examined who collected a free bottle of hand sanitizer towards the end of the first swine flu pandemic wave in December 2009. Methods: 629 participants took part in a longitudinal study assessing perceived likelihood and severity of an H1N1 infection, and H1N1 influenza related negative affect (i.e., feelings of threat, concern, and worry) at T1 (October 2009, week 43-44) and T2 (December 2009, week 51-52). Importantly, all participants received a voucher for a bottle of hand sanitizer at T2 which could be redeemed in a university office newly established for this occasion at T3 (ranging between 1-4 days after T2). Results: Both a sequential longitudinal model (M2) as well as a change score model (M3) showed that greater perceived likelihood and severity at T1 (M2) or changes in perceived likelihood and severity between T1 and T2 (M3) did not directly drive protective behavior (T3), but showed a significant indirect impact on behavior through H1N1 influenza related negative affect. Specifically, increases in perceived likelihood (&bgr; = .12), severity (&bgr; = .24) and their interaction (&bgr; = .13) were associated with a more pronounced change in negative affect (M3). The more threatened, concerned and worried people felt (T2), the more likely they were to redeem the voucher at T3 (OR = 1.20). Conclusions: Affective components need to be considered in health behavior models. Perceived likelihood and severity of an influenza infection represent necessary but not sufficient self-referential knowledge for paving the way for preventive behaviors. [ABSTRACT FROM AUTHOR]

Background: Use of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca2+-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects. Methods: To address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies. Results: Although both cell types express TRPV1 mRNA, neither responded to vanilloids withCa2+-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1-50 nM) of vanilloids. The TRPV1-mediated and nonreceptor specificCa2+-cytotoxity ([RTX]>15 μM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediatedCa2+-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes. Conclusion: TRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials. [ABSTRACT FROM AUTHOR]

Background: Despite increasingly frequent bacterial resistance to antibiotics, antibacterial innovation is rare. Ketolides constitute one of the very few new antibiotic classes active against Streptococcus pneumoniae developed during the last 25 years. Their mechanism of action resembles that of macrolides, but they are unaffected by common resistance mechanisms. However, cross-resistance to ketolides has been observed in some macrolide-resistant strains. We examined how new antibiotic exposure may affect overall pneumococcal resistance patterns in the population. The aims of this study were to assess the potential dissemination of newly emerged resistances and to control the selection of strains already multiresistant to existing antimicrobials. Methodology/Principal Findings: We developed an age-structured population model for S. pneumoniae transmission in a human community exposed to heptavalent vaccine, and β-lactams, macrolides and ketolides. The dynamics of intraindividual selection of resistant strains under antibiotic exposure and interindividual transmission were simulated, with antibiotic-specific resistance mechanisms defining the path to co-resistances and cross-resistances, and parameters concerning the French situation. Results of this simulation study suggest that new antibiotic consumption could markedly slow the diffusion of multiresistant strains. Wider use was associated with slower progression of multiresistance. When ketolides were prescribed to all ages, resistance to them reached 10% after .15 years, while it took .40 years when they were prescribed only to adults. In the scenario according to which new antibiotics totally replaced former antimicrobials, the β-lactam resistance rate was limited at 70%. Conclusions: In a context of widespread vaccination and rational use of antibiotics, innovative antibiotic, prescribed to all age groups, may have an added impact on multiresistant-strain dissemination in the population. [ABSTRACT FROM AUTHOR]

Background / Aims:ClO2, the so-called “ideal biocide”, could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. Methods:ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. Results:The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e.g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. Conclusion:Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic. [ABSTRACT FROM AUTHOR]