Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach.

Pseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.

Marine Fungal Cerebroside Flavuside B Protects HaCaT Keratinocytes against Staphylococcus aureus Induced Damage.

Cerebrosides are glycosylated sphingolipids, and in mammals they contribute to the pro-/anti-inflammatory properties and innate antimicrobial activity of the skin and mucosal surfaces. Staphylococcus aureus infection can develop, not only from minor scratches of the skin, but this pathogen can also actively promote epithelial breach. The effect of cerebroside flavuside B from marine sediment-derived fungus Penicillium islandicum (Aniva Bay, the Sea of Okhotsk) on viability, apoptosis, total caspase activity, and cell cycle in human epidermal keratinocytes HaCaT line co-cultivated with S. aureus, as well as influence of flavuside B on LPS-treated HaCaT cells were studied. Influence of flavuside B on bacterial growth and biofilm formation of S. aureus and its effect on the enzymatic activity of sortase A was also investigated. It was found S. aureus co-cultivated with keratinocytes induces caspase-depended apoptosis and cell death, arrest cell cycle in the G0/G1 phase, and increases in cellular immune inflammation. Cerebroside flavuside B has demonstrated its antimicrobial and anti-inflammatory properties, substantially eliminating all the negative consequences caused by co-cultivation of keratinocytes with S. aureus or bacterial LPS. The dual action of flavuside B may be highly effective in the treatment of bacterial skin lesions and will be studied in the future in in vivo experiments.

NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence.

During skin injury, immune response and repair mechanisms have to be coordinated for rapid skin regeneration and the prevention of microbial infections. Natural Killer (NK) cells infiltrate hypoxic skin lesions and Hypoxia-inducible transcription factors (HIFs) mediate adaptation to low oxygen. We demonstrate that mice lacking the Hypoxia-inducible factor (HIF)-1α isoform in NK cells show impaired release of the cytokines Interferon (IFN)-γ and Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) as part of a blunted immune response. This accelerates skin angiogenesis and wound healing. Despite rapid wound closure, bactericidal activity and the ability to restrict systemic bacterial infection are impaired. Conversely, forced activation of the HIF pathway supports cytokine release and NK cell-mediated antibacterial defence including direct killing of bacteria by NK cells despite delayed wound closure. Our results identify, HIF-1α in NK cells as a nexus that balances antimicrobial defence versus global repair in the skin.

Cutaneous anthrax associated with handling carcasses of animals that died suddenly of unknown cause: Arua District, Uganda, January 2015-August 2017.

BACKGROUND: Anthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May-June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidence-based control measures. METHODS: A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015-August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths. RESULTS: There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30-39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3-11), butchering (ORM-H = 22, 95%CI: 5.5-89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95%CI: 3.0-16) were associated with illness. CONCLUSIONS: Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015-2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly.

Aqueous chlorhexidine 1% versus 2% for neonatal skin antisepsis: a randomised non-inferiority trial.

OBJECTIVE: To evaluate whether 1% aqueous chlorhexidine gluconate (CHG) when compared with 2% aqueous chlorhexidine gluconate is non-inferior for neonatal skin antisepsis. DESIGN: Parallel, blinded, non-inferiority randomised trial. SETTING: Level III, academic, neonatal intensive care unit. PATIENTS: Infants born at 260/7 to 426/7 weeks of gestation from June 2019 to December 2019. INTERVENTIONS: Participants were randomised to skin antisepsis by either 1% aqueous CHG or 2% aqueous CHG. MAIN OUTCOME MEASURES: The primary outcome was the proportion of negative skin swab cultures after skin antisepsis. Secondary outcomes were local skin reactions at 0, 6, 12 and 24 hours and plasma chlorhexidine levels in a subset of the study population. RESULTS: A total of 308 neonates with a median gestation age of 34 (31-37) weeks and mean birth weight of 2029 g were randomised on 685 occasions (1% CHG: n=341; 2% CHG: n=344). 93.0% of the post-antisepsis skin swabs were sterile in 1% CHG group compared with 95.6% of the swabs in the 2% CHG group (risk difference -2.7%, 95% CI -6.2% to +0.8%). The lower bound of 95% CI crossed the pre-specified absolute non-inferiority limit of 5%. Neonates developed mild dermatitis on 16 (2.3%) occasions. There was no significant difference in median plasma CHG levels in the two groups, 19.6 (12.5-36.4) and 12.6 (8.7-26.6) ng/mL, respectively. CONCLUSIONS: Application of 1% aqueous CHG was not shown to be non-inferior to 2% chlorhexidine aqueous for skin antisepsis in neonates. There were no severe skin-related adverse events in either of the two groups. TRIAL REGISTRATION NUMBER: CTRI/2019/06/019822; (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=33453&EncHid=&userName=CTRI/2019/06/019822).

Dual bio-active factors with adhesion function modified electrospun fibrous scaffold for skin wound and infections therapeutics.

Electrospun fibrous scaffolds combined with bioactive factors can display impressive performance as an ideal wound dressing, since they can mimic the composition and physicochemical properties of the extracellular matrix (ECM). The aim of this study was to fabricate a new composite biomaterial (IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffold) for wound healing, using a rat model for experimental evaluation. A small pentapeptide tag composed of DA-Lys-DA-Lys-DA residues was introduced into insulin-like growth factor 1 (IGF1) and the antimicrobial peptide Os to prepare IGF1 and Os modified with 3,4-dihydroxyphenylalanine (DA) (IGF1-DA and Os-DA). The designed chimeric growth factor and antimicrobial peptide could successfully anchor to PLGA electrospun fibrous scaffolds, and the growth factor and antimicrobial peptide could be controllably released from the electrospun fibrous scaffolds. The results showed that the IGF1-DA and Os-DA-modified PLGA electrospun fibrous scaffolds (PLGA/Os-DA/IGF1-DA) exhibited high hydrophilicity and antimicrobial activity; moreover, the porous network of the scaffolds was similar to that of the natural ECM, which can provide a favourable environment for BALB/C 3T3 cells growth. The in vivo application of PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds in rat skin wounds resulted in improved wound recovery and tissue regeneration rate. The experimental results indicated that the IGF1-DA and Os-DA could effectively bind to PLGA electrospun fibrous scaffolds, promote wound healing and prevent infection in rats, thereby suggesting that PLGA/Os-DA/IGF1-DA electrospun fibrous scaffolds have a wide application value in the field of skin wound repair.

Resistin-like Molecule α Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin.

Vitamin A deficiency increases susceptibility to skin infection. However, the mechanisms by which vitamin A regulates skin immunity remain unclear. Here, we show that resistin-like molecule α (RELMα), a small secreted cysteine-rich protein, is expressed by epidermal keratinocytes and sebocytes and serves as an antimicrobial protein that is required for vitamin-A-dependent resistance to skin infection. RELMα was induced by microbiota colonization of the murine skin, was bactericidal in vitro, and was protected against bacterial infection of the skin in vivo. RELMα expression required dietary vitamin A and was induced by the therapeutic vitamin A analog isotretinoin, which protected against skin infection in a RELMα-dependent manner. The RELM family member Resistin was expressed in human skin, was induced by vitamin A analogs, and killed skin bacteria, indicating a conserved function for RELM proteins in skin innate immunity. Our findings provide insight into how vitamin A promotes resistance to skin infection.

Impact of Trimethoprim-sulfamethoxazole Urinary Tract Infection Prophylaxis on Non-UTI Infections.

In this secondary analysis of the Randomized Intervention for Children with Vesicoureteral Reflux cohort, we found that daily prophylaxis with trimethoprim-sulfamethoxazole was not associated with an increased or decreased risk of skin and soft tissue infections, pharyngitis or sinopulmonary infections in otherwise healthy children 2-71 months of age.

A cutaneous Anthrax outbreak in Koraput District of Odisha-India 2015.

BACKGROUND: Cutaneous anthrax in humans is associated with exposure to infected animals or animal products and has a case fatality rate of up to 20% if untreated. During May to June 2015, an outbreak of cutaneous anthrax was reported in Koraput district of Odisha, India, an area endemic for anthrax. We investigated the outbreak to identify risk factors and recommend control measures. METHOD: We defined a cutaneous anthrax case as skin lesions (e.g., papule, vesicle or eschar) in a person residing in Koraput district with illness onset between February 1 and July 15, 2015. We established active surveillance through a house to house survey to ascertain additional cases and conducted a 1:2 unmatched case control study to identify modifiable risk factors. In case control study, we included cases with illness onset between May 1 and July 15, 2015. We defined controls as neighbours of case without skin lesions since last 3 months. Ulcer exudates and rolled over swabs from wounds were processed in Gram stain in the Koraput district headquarter hospital laboratory. RESULT: We identified 81 cases (89% male; median age 38 years [range 5-75 years]) including 3 deaths (case fatality rate = 4%). Among 37 cases and 74 controls, illness was significantly associated with eating meat of ill cattle (OR: 14.5, 95% CI: 1.4-85.7) and with close handling of carcasses of ill animals such as burying, skinning, or chopping (OR: 342, 95% CI: 40.5-1901.8). Among 20 wound specimens collected, seven showed spore-forming, gram positive bacilli, with bamboo stick appearance suggestive of Bacillus anthracis. CONCLUSION: Our investigation revealed significant associations between eating and handling of ill animals and presence of anthrax-like organisms in lesions. We immediately initiated livestock vaccination in the area, educated the community on safe handling practices and recommended continued regular anthrax animal vaccinations to prevent future outbreaks.

An economic case for a vaccine to prevent group A streptococcus skin infections.

BACKGROUND: Group A streptococcus (GAS) causes an exceptionally diverse range of diseases, raising questions about the optimal product characteristics of a commercially viable vaccine. The objectives of this study were to (1) estimate the current health and economic burdens caused by 24 diseases attributable to GAS each year in Australia and (2) use these estimates to explore the value of a GAS vaccine for different clinical indications, age schedules, and population groups. METHODS: For objective 1, we estimated the population heath and economic burdens by synthesising data from administrative databases, nationally representative surveys, literature reviews, public reimbursement schedules, and expert opinion. For objective 2, we modelled the prospective lifetime burden of GAS for all infants from birth, for children from 5 years of age, and for adults from 65 years of age. A vaccine was assumed to reduce each GAS disease by 70% for a period of 10 years, and the difference in outcomes between vaccinated and non-vaccinated cohorts were used to calculate the cost-effective value of vaccination. RESULTS: The annual health and economic burdens of GAS diseases totalled 23,528 disability-adjusted life years and AU$185.1 million in healthcare costs respectively; approximately half of each measure was due to cellulitis, followed by other skin infections and throat infections. Reducing the incidence of throat infections, skin infections, and cellulitis in non-Indigenous cohorts resulted in 30%, 33%, and 28% of the total vaccine value for an infant schedule (cost-effective vaccine price AU$260 per course); 47%, 26%, and 22% of the value for a child schedule (AU$289); and 2%, 15% and 74% for an adult schedule (AU$489). CONCLUSIONS: A vaccine that prevents GAS cellulitis and other skin infections, in addition to throat infections, would maximise its value and commercial viability, with a cost-effective price in line with other recently-licensed and funded vaccines in Australia.

Need for improved public health protection of young people wanting body piercing: evidence from a look-back exercise at a piercing and tattooing premises with poor hygiene practices, Wales (UK) 2015.

Following a cluster of serious pseudomonas skin infections linked to a body piercing and tattooing premises, a look-back exercise was carried out to offer clients a screen for blood-borne viruses. Of those attending for screening 72% (581/809) had a piercing procedure in the premises of interest: 94 (16%) were under 16 years of age at the time of screening. The most common site of piercing was ear (34%), followed by nose (27%), nipple (21%) and navel (21%). A small number (<5) tested positive for hepatitis B and C, with no evidence this was linked to the premises. However, 36% (211/581) of clients reported a skin infection associated with their piercing. Using data from client forms, 36% provided a false age. Those aged under 16 years (OR 4.5, 95% CI 2.7-7.7) and those receiving a piercing at an intimate site (OR 2.1, 95% CI 1.3-3.6) were more likely to provide a false age. The findings from this exercise were used to support the drafting of the Public Health (Wales) Bill which proposed better regulation of piercing premises and the need to provide proof of being 18 years of age or over before having a piercing of an intimate site.

Antiseptic Agents Elicit Short-Term, Personalized, and Body Site-Specific Shifts in Resident Skin Bacterial Communities.

Despite critical functions in cutaneous health and disease, it is unclear how resident skin microbial communities are altered by topical antimicrobial interventions commonly used in personal and clinical settings. Here we show that acute exposure to antiseptic treatments elicits rapid but short-term depletion of microbial community diversity and membership. Thirteen subjects were enrolled in a longitudinal treatment study to analyze the effects of topical treatments (i.e., ethanol, povidone-iodine, chlorhexidine, and water) on the skin microbiome at two skin sites of disparate microenvironment: forearm and back. Treatment effects were highly dependent on personalized and body site-specific colonization signatures, which concealed community dynamics at the population level when not accounted for in this analysis. The magnitude of disruption was influenced by the identity and abundance of particular bacterial inhabitants. Lowly abundant members of the skin microbiota were more likely to be displaced, and subsequently replaced, by the most abundant taxa prior to treatment. Members of the skin commensal family Propionibactericeae were particularly resilient to treatment, suggesting a distinct competitive advantage in the face of disturbance. These results provide insight into the stability and resilience of the skin microbiome, while establishing the impact of topical antiseptic treatment on skin bacterial dynamics and community ecology.

Can community health workers identify omphalitis? A validation study from Southern Province, Zambia.

OBJECTIVE: Omphalitis, or umbilical cord infection, is an important cause of newborn morbidity and mortality in low-resource settings. We tested an algorithm that task-shifts omphalitis diagnosis to community-level workers in sub-Saharan Africa. METHODS: Community-based field monitors and Zambian paediatricians independently evaluated newborns presenting to health facilities in Southern Zambia using a signs and symptoms checklist. Responses were compared against the paediatrician's gold standard clinical diagnosis. RESULTS: Of 1009 newborns enrolled, 6.2% presented with omphalitis per the gold standard clinical diagnosis. Paediatricians' signs and symptoms with the highest sensitivity were presence of pus (79.4%), redness at the base (50.8%) and newborn flinching when cord was palpated (33.3%). The field monitor's signs and symptoms answers had low correlation with paediatrician's answers; all signs and symptoms assessed had sensitivity <16%. CONCLUSION: Despite extensive training, field monitors could not consistently identify signs and symptoms associated with omphalitis in the sub-Saharan African setting.

Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome.

We describe a case of Omenn syndrome displaying exudative erythroderma and other characteristic features, including alopecia, absent B and naïve T cells, hyper immunoglobulin E levels, and eosinophilia. A pathogenic recombination-activating RAG1 homozygous genetic mutation confirmed the diagnosis. She required frequent antibiotics at both treatment and prophylactic doses, which alone did not control her erythroderma, but her high risk of infection precluded the use of systemic agents such as cyclosporine, which would further suppress her already severely compromised immune system. Thrice-weekly topical dilute hypochlorite compresses, combined with skin acidification with a low pH emollient, were initiated to control inflammation and for cutaneous bacterial prophylaxis. She demonstrated a marked improvement in her erythroderma within days after treatment initiation. Further improvement continued with the addition of systemic corticosteroids, with resolution of erythroderma after her first dose. This case reveals for the first time that dilute topical hypochlorite and skin pH restoration holds promise to control severe dermatitis associated with immunodeficiency and inflammatory syndromes with minimal side effects.

Effects of bathing interval on skin condition and axillary bacterial colonization in preterm infants.

AIM: The objective of this study was to evaluate the effects of preterm infant bathing periods on skin condition and axillary skin colonization. BACKGROUND: Reducing the frequency of bathing in preterm infants is beneficial in reducing the risk of hypothermia and exposure to stress from frequent nursing contacts. METHODS: The subjects of this study were observed at The V hospital at the C University in South Korea between December 2012 and August 2013. A total of 32 preterm infants were included and were randomly assigned to two different bathing intervals; every four days (n=16) and the other every two days (n=16) bathing groups. A neonatal skin conditions were assessed on a daily basis, whereas, axillary skin colonization was measured every eight days before bathing. Data was analyzed via the SPSS program with a non-inferiority test, t-test, chi-square test, Fisher's exact test, and paired t-test. RESULTS: Mean differences of skin condition between the four-day bathing and two-day bathing groups were 0.065 and the 97.5% one-sided confidence limit was 0.196 (less than the non-inferiority margin, 0.3). There were no statistically significant differences in skin condition and axillary skin colonization between the two groups (p>0.05). CONCLUSION: The interval of bathing for preterm infants can be changed from every two days to every four days without increasing the incidence of skin condition problems or axillary skin colonization. Less-frequent bathing may decrease the chance of physiological instability caused by the caring process, while providing them with a better environment for growth and development.

Effect of prophylactic cefalexin treatment on the development of bacterial infection in acute radiation-induced dermatitis in dogs: a blinded randomized controlled prospective clinical trial.

BACKGROUND: Acute radiation-induced dermatitis (ARID) is a common sequela of radiation therapy and carries the risk of secondary bacterial skin infection. No standard of care exists for managing canine ARID and evidence-based guidelines are lacking; however, prophylactic use of antibiotics is common. HYPOTHESIS/OBJECTIVES: To evaluate the impact of prophylactic cefalexin on the prevalence and severity of bacterial infection in canine ARID. ANIMALS: Seventeen dogs treated with definitive-intent radiotherapy. METHODS: All dogs were treated with definitive-intent radiation therapy (48-57.5 gray) targeted to the skin surface. Dogs were randomized to receive either prophylactic cefalexin (22 mg/kg twice daily) beginning halfway through the prescribed radiotherapy course (cohort A) or to serve as controls (cohort B). Aerobic skin cultures and surface cytological evaluation were performed at first onset of moist desquamation and one week following completion of radiation therapy. Skin toxicity grading and owner quality of life (QoL) questionnaires were performed weekly. The rate of infection, multidrug resistance status, toxicity severity and QoL between cohorts were compared. RESULTS: Staphylococcus schleiferi and S. pseudintermedius were the most frequent bacterial agents isolated in both cohorts. There was no significant difference in prevalence of bacterial infection or overall QoL between cohorts at either time point; however, multidrug-resistant infections were significantly increased in cohort A versus cohort B. Clinician- and client-perceived severity of toxicity was significantly greater and median duration of moist desquamation was significantly longer in cohort A than cohort B. CONCLUSIONS AND CLINICAL IMPORTANCE: Prophylactic use of cefalexin for management of canine ARID is not recommended.

Systematic literature review to identify methods for treating and preventing bacterial skin infections in Indigenous children.

BACKGROUND/OBJECTIVES: Bacterial skin infections in Indigenous children in Australia frequently lead them to access primary health care. This systematic review aims to identify and analyse available studies describing the treatment and prevention of bacterial skin infections in Indigenous children. METHODS: Electronic databases including Scopus, MEDLINE, CINAHL, ProQuest, Informit and Google Scholar were searched. Studies in English published between August 1994 and September 2016, with the subject of bacterial skin infections involving Indigenous children and conducted in Australia, New Zealand, the USA or Canada were selected. RESULTS: Initially 1474 articles were identified. After the application of inclusion and exclusion criteria, 10 articles remained. Strategies for the treatment and prevention of bacterial skin infections included the management of active infections and lesions, improving environmental and personal hygiene, the installation of swimming pools and screening and treatment. CONCLUSION: There is a need for more, rigorous, large-scale studies to develop evidence for appropriate, culturally acceptable methods to prevent and manage bacterial skin infections in Indigenous children in Australia. The problem is complex with multiple determinants. Until underlying socioeconomic conditions are addressed skin infections will continue to be a burden to communities.

Neonatal skin care: what should we do? A four-week follow-up randomized controlled trial at Zagazig University Hospitals.

INTRODUCTION: Taking care of newborn skin is necessary to avoid skin infections. The normal daily exposure to external factors affects the skin negatively. Skin hygiene and proper skin cleansing as well as protection of the infant skin barrier are essential to maintain barrier function and overall infant health. AIM: The aim of this work is to assess the neonatal skin care effectiveness in promotion of normal skin development and protection of the optimal skin function by avoiding the different neonatal skin disorders which cause skin infection. CONCLUSION: In conclusion, proper care and good hygiene of the normal mature neonatal skin are essential to maintain skin barrier function and overall health. This is achieved by optimizing epidermal barrier integrity that includes: bathing and using emollient; preventing and managing infections and skin injury; minimizing transepidermal water loss (TEWL); minimizing heat loss and percutaneous absorption of toxins. Baby bath products as well as baby wipes are safe to use and do not appear to affect an infant's skin barrier integrity. It is therefore sensible to use cleansers that have been specially designed for baby's skin, which are pH neutral and very mild to avoid irritant dermatitis and allergic dermatitis.