Host-Microbe Interaction on the Skin and Its Role in the Pathogenesis and Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a condition with a complex and unclear aetiology. Possible causes of AD encompass alterations in the structure and function of the epidermal barrier, disturbances in the skin microbiome, immune factors, allergens, bacterial and fungal infections as well as environmental and genetic factors. In patients with AD, acute skin lesions are colonized by a greater number of bacteria and fungi than chronic lesions, clinically unchanged atopic skin and the skin of healthy people. Mechanisms promoting skin colonization by pathogens include complex interplay among several factors. Apart from disturbances of the skin microbiome, increased adhesion in atopic skin, defects of innate immune response resulting in the lack of or restriction of growth of microorganisms also contribute to susceptibility to the skin colonization of and infections, especially with Staphylococcus aureus. This review of the literature attempts to identify factors that are involved in the pathogenesis of AD-related bacterial and fungal skin colonization. Studies on the microbiome, commensal microorganisms and the role of skin microorganisms in maintaining healthy skin bring additional insight into the treatment and prevention of AD. In the light of presented mechanisms, reduction in colonization may become both causative and symptomatic treatment in AD.

Tools for detecting a “superbug”: updates on Candida auris testing

Candida auris is an emerging yeast species that has the unique characteristics of patient skin colonization and rapid transmission within healthcare facilities and the ability to rapidly develop antifungal resistance. When C. auris first started appearing in clinical microbiology laboratories, it could only be identified using DNA sequencing. In the decade since its first identification outside of Japan there have been many improvements in the detection of C. auris . These include the expansion of MALDI-TOF databases to include C. auris , the development of both laboratory-developed tests and commercially available kits for its detection, and special CHROMagar for identification from laboratory specimens. Here we discuss the current tools and resources that are available for C. auris identification and detection.

Efficacy of a Retinoid, Keratolytic, Anti-Inflammatory and Antibacterial Gel and Spray Formulations in Mild Common Acne

Background and Objectives: For the treatment of mild/moderate acne, topical retinoids and antibacterial molecules are used in monotherapy or in combination. An exfoliating and anti-inflammatory action can increase the clinical efficacy of this therapeutic approach. A topical product in Gel and Spray Formulations (GF and SF) with retinoids (hydroxypinacolone retinoate and encapsulated retinol), with anti-inflammatory (niacinamide), antibacterial (biopep15) and keratolytic (glycolic and salicylic acids) activity has recently been developed. Topical retinoids have anti-inflammatory, anti-seborrheic and anticomedone-formation properties. Biopep15 is an oligopeptide with antibacterial action that can interfere with lipoteichoic acid, a component of the wall of Cutibacterium acnes. In addition, Biopep15 can perform also an antagonistic action against the Toll-Like-Receptor 2, involved in the pathogenesis of acne. Niacinamide has a well-known anti-inflammatory action. Salicylic and glycolic explain keratolytic and exfoliating activities. In this study the objective was to determine the efficacy and tolerability of GF and SF in mild/ moderate comedogenic acne. Methods: In a 4-week, open-label, prospective trial, 32 patients between the ages of 15 and 30 have been evaluated. All participants gave their written consent. Treatment with gel (for facial lesions) and spray (for lesions located on thorax, back and shoulder) applied twice daily were used. To assess clinical efficacy, a count of comedogenic lesions (open and closed comedones; non-inflammatory lesions: NIL) and inflammatory lesions (IL; papules, and pustules) was performed and the reduction in the number of lesions after 2 and 4 weeks of treatment was evaluated. An evaluation of Total lesions count (TL; NIL+IL) was also performed.The lesion count data were analysed with a paired Student's t test.We evaluated also the exfoliating/keratolytic activity and the effect on sebum production assessed at baseline, after 2 and 4 weeks of treatment. Finally, to evaluate Cutibacterium acnes (C. acnes) skin colonization, we performed a fluorescence detection of skin porphyrin content at baseline and at day 28, by mean of Visiopor PP 34 camera. Results: All patients completed the trial. At baseline the NIL, IL and TL count were 14.3, 8.7 and23, respectively. After 2 weeks of GF/SF treatment, NIL, IL and TL significantly decreased to 9.7 (-32%), 6.8 (-22%) and 16.5 (-29%), respectively. At the end of the treatment, a significant reduction in comparison with baseline was observed for NIL (-49%) IL (-63%) and TL (-54%). The exfoliating index evaluated in comparison with baseline value improved not significantly by 13% at day 14, and significantly (p=0.05) by 18% at day 24. The Cutibacterium acnes skin colonization area was significantly (p=0.02) reduced by 28% in comparison with baseline. Treatment was well tolerated, and local tolerability was assessed as optimal by all patients. Conclusion: This new anti-acne combination formula based on retinoids, antibacterial oligopeptide, keratolytic and anti-inflammatory agents have shown high clinical efficacy and good tolerability in patients with mild to moderate acne. The treatment shows also a keratolytic effect and a significant reduction of C. acnes skin colonization.

The effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe atopic dermatitis (ABC trial): study protocol for a pragmatic randomized controlled trial

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 10 to 20% of children and between 2 and 15% of the adults in Western Europe. Since 2000, therapeutic clothing or functional textiles based on silver or chitosan as antibacterial agents were introduced for AD. These agents aim to reduce skin colonization with Staphylococcus (S.) aureus. Increased colonization with S. aureus is correlated with increased AD severity. The antimicrobial effects of silver and chitosan have been demonstrated before. At this point, there is insufficient evidence for the effectiveness of antibacterial therapeutic clothing in patients with AD. Methods This is a pragmatic randomized controlled double-blind multi-center trial comparing the effectiveness of antibacterial therapeutic clothing based on silver or chitosan as compared with non-antibacterial therapeutic clothing in patients with moderate to severe AD. A total of 165 participants, aged 0 to 80, diagnosed with moderate to severe AD are included. The study is performed in the Erasmus MC University Medical Center, University Medical Center Groningen, University Medical Center Utrecht, Amsterdam University Medical Centers, and St. Antonius Hospital Nieuwegein. Patients will be randomized 1:1:1 into one of the three intervention groups: group A will receive therapeutic clothing without antimicrobial agents, group B will receive microbial growth reducing therapeutic clothing based on chitosan, and group C will receive antimicrobial clothing based on silver. All therapeutic clothing is to be worn at night during the 12-month intervention period. Usual care is continued. The primary objective is to assess the effectiveness of antibacterial clothing (silver and chitosan group) as compared to non-antibacterial clothing assessed with the Eczema Area and Severity Index at 12 months compared to baseline. Secondary outcomes include between-group differences in physician- and patient-reported outcome measures, topical therapy use, S. aureus skin colonization, and safety. Data will be collected at baseline and after 1 month, 3 months, 6 months, and 12 months. A cost-effectiveness analysis will be performed. Discussion This trial will provide data on the effectiveness, cost-effectiveness, and safety of antibacterial therapeutic clothing for patients with AD. Trial registration ClinicalTrials.gov NCT04297215. Registered on 5 March 2020

768. Gaining Compliance-Getting Results

Background Compliance with the chlorhexidine gluconate (CHG) daily application component of the CLABSI prevention bundle potentially could negatively affect infection rates. In an attempt to increase CHG compliance, a 3-month trial for soap based CHG bathing was undertaken on two pediatric oncology units with long term central line patients. Methods The current bathing process involved 2 steps, a soap and water bath followed one hour later by a CHG wipe. It was time consuming and received complaints from staff and parents resulting in lower documented compliance rates. A one step process was implemented combining skin cleansing and CHG application with one product. Staff, parents and patients were educated on proper bathing technique. Instruction brochures printed in multiple languages were employed and discussed for education. An electronic survey was developed to collect parent feedback. Results The trial was from October - December 2020 and included 25 select patients in the cancer center. Patients and parents provided positive feedback with the new process. Audits measured both line maintenance and bathing. If one step was missed-than non- compliance with the bundle was noted . Bundle adherence increased with auditors noting that this was due entirely to an increase in bathing compliance. From April to September 2020 prior to implementation of the soap based CHG bathing, CHG compliance on the Stem Cell Transplant Unit (SCTU) averaged 48%. During the three month period after the trial, CHG compliance has averaged 64%. CHG monthly compliance reached 85% by April 2021. In addition, patients compliant with CHG bathing demonstrated a significant reduction in coagulase negative staphylococcus (CoNS ) blood stream infections due to the reduction of CoNS skin colonization. Cost analysis for the one week in the 15 bed BMT unit and 10 HemONC patients showed that the one step soap based CHG was &161.50 and the CHG wipe cost &960,75; a difference of &799.25per week or &41,561.00 annually. Conclusion Any infection prevention strategy needs to involve staff and parents for compliance and outcome success. Disclosures All Authors: No reported disclosures

Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.

Augmenting the Activity of Chlorhexidine for Decolonization of Candida auris from Porcine skin

Candida auris readily colonizes skin and efficiently spreads among patients in healthcare settings worldwide. Given the capacity of this drug-resistant fungal pathogen to cause invasive disease with high mortality, hospitals frequently employ chlorhexidine bathing to reduce skin colonization. Using an ex vivo skin model, we show only a mild reduction in C. auris following chlorhexidine application. This finding helps explain why chlorhexidine bathing may have failures clinically, despite potent in vitro activity. We further show that isopropanol augments the activity of chlorhexidine against C. auris on skin. Additionally, we find both tea tree (Melaleuca alternifolia) oil and lemongrass (Cymbopogon flexuosus) oil to further enhance the activity of chlorhexidine/isopropanol for decolonization. We link this antifungal activity to individual oil components and show how some of these components act synergistically with chlorhexidine/isopropanol. Together, the studies provide strategies to improve C. auris skin decolonization through the incorporation of commonly used topical compounds.

Meta-analysis of the efficacy of preoperative skin preparation with alcoholic chlorhexidine compared to povidone iodine in orthopedic surgery

Preoperative skin preparation is an effective method to prevent surgical site infections (SSI). Alcoholic chlorhexidine (CHG) and povidone iodine (PV-I) are the most widely used antiseptic agents. This meta-analysis aims to determine their efficacy in reducing natural bacterial skin flora in clean orthopedic surgery. A systematic search was conducted through current literature up to June 2021 to identify clinical randomized trials that compared the efficacy of alcoholic chlorhexidine and povidone iodine in reducing bacterial skin colonization after preoperative skin preparation. A meta-analysis was conducted. Of 235 screened articles, 8 randomized controlled trials were included. The results of the meta-analysis demonstrate a significantly lower positive culture rate in the chlorhexidine group than in the povidone iodine group (RR = 0.53, 95% Cl: 0.32–0.88). The present data show the superiority of chlorhexidine in reducing the normal bacterial flora compared to povidone iodine in clean orthopedic surgery.