Does hydrogen peroxide application to the dermis following surgical incision affect Cutibacterium acnes cultures in total shoulder arthroplasty in male patients? A randomized controlled trial.

BACKGROUND: Periprosthetic joint infections occur in 1%-4% of primary total shoulder arthroplasties (TSAs). Cutibacterium acnes is the most commonly implicated organism and has been shown to persist in the dermis despite use of preoperative antibiotics and standard skin preparations. Studies have shown decreased rates of cultures positive for C acnes with use of preoperative benzoyl peroxide or hydrogen peroxide (H2O2), but even with this positive deep cultures remain common. We sought to determine whether an additional application of H2O2 directly to the dermis following skin incision would further decrease deep culture positivity rates. METHODS: We performed a randomized controlled trial comparing tissue culture results in primary TSA in patients who received a standard skin preparation with H2O2, ethanol, and ChloraPrep (CareFusion, Leawood, KS, USA) vs. an additional application of H2O2 to the dermis immediately after skin incision. Given the sexual dimorphism seen in the shoulder microbiome regarding C acnes colonization rates, only male patients were included. Bivariable and multivariable analyses were performed to compare rates of positive cultures based on demographic and surgical factors. RESULTS: Dermal cultures were found to be positive for C acnes at similar rates between the experimental and control cohorts for the initial (22% vs. 28%, P = .600) and final (61% vs. 50%, P > .999) dermal swabs. On bivariable analysis, the rate of positive deep cultures for C acnes was lower in the experimental group, but this difference was not statistically significant (28% vs. 44%, P = .130). However, patients who underwent anatomic TSA were found to have a significantly greater rate of deep cultures positive for C acnes (57% vs. 28%, P = .048); when controlling for this on multivariable analysis, the experimental cohort was found to be associated with significantly lower odds of having positive deep cultures (odds ratio, 0.37 [95% confidence interval, 0.16-0.90], P = .023). There were no wound complications in either cohort. CONCLUSIONS: An additional H2O2 application directly to the dermis following skin incision resulted in a small but statistically significant decrease in the odds of having deep cultures positive for C acnes without any obvious adverse effects on wound healing. Given its cost-effectiveness, use of a post-incisional dermal decontamination protocol may be considered as an adjuvant to preoperative use of benzoyl peroxide or H2O2 to decrease C acnes contamination.

Characterization of skin surface and dermal microbiota in dogs with mast cell tumor.

The skin microbiota interacts with the host immune response to maintain the homeostasis. Changes in the skin microbiota are linked to the onset and the progression of several diseases, including tumors. We characterized the skin surface and dermal microbiota of 11 dogs affected by spontaneous mast cell tumor (MCT), using skin contralateral sites as intra-animal healthy controls. The microbial profile differed between healthy and tumor skin surfaces and dermis, demonstrating that the change in microbiota composition is related to the presence of MCT. The number of observed taxa between MCT and healthy skin surfaces was detected, showing a decrease in number and heterogeneity of taxa over the skin surface of MCT, at both inter- and intra-individual level. Preliminary data on bacterial population of MCT dermis, obtained only on three dogs, demonstrated an intra-individual reduction of taxa number when compared to the skin surface. Taxonomy reveals an increase of Firmicutes phylum and Corynebacteriaceae family in MCT skin surface when compared to the healthy contralateral. In conclusion, we demonstrate that microbial population of skin surface and dermis is related to mast cell tumor. Our study provides the basis for future investigations aiming to better define the interaction between mast cell tumors, microbiota and host immune response.

Case for diagnosis. Keloidal cord-like lesion on the leg

Abstract We report a 74-year-old male presented to an outpatient dermatology clinic in Manaus, Amazonas, with a one-year history of pruritic, keloidal lesions on his left lower extremity. Histopathology showed round structures in reticular dermis. Grocott methenamine silver stain revealed numerous round yeasts with thick double walls, occurring singly or in chains connected by tubular projections. The diagnosis was lobomycosis. Although the keloidal lesions presented by this patient are typical of lobomycosis, their linear distribution along the left lower limb is unusual.

What is your diagnosis? Keloidal cord-like lesion on the leg.

We report a 74-year-old male presented to an outpatient dermatology clinic in Manaus, Amazonas, with a one-year history of pruritic, keloidal lesions on his left lower extremity. Histopathology showed round structures in reticular dermis. Grocott methenamine silver stain revealed numerous round yeasts with thick double walls, occurring singly or in chains connected by tubular projections. The diagnosis was lobomycosis. Although the keloidal lesions presented by this patient are typical of lobomycosis, their linear distribution along the left lower limb is unusual.

Strategies to decolonize the shoulder of Cutibacterium acnes: a review of the literature.

Cutibacterium acnes is the most prevalent cause of joint infection after shoulder surgery. Current methods for decolonizing this bacterium from the shoulder region have proved ineffective owing to its unique niche within dermal sebaceous glands and hair follicles. When we are making decisions to decolonize the skin of C acnes, the risks associated with decolonization must be balanced by the potential benefits of reduced deep tissue inoculation. The purpose of this review was to describe currently available methods of decolonization and their efficacy.

Universal Dermal Microbiome in Human Skin.

Human skin microbiota has been described as a "microbial fingerprint" due to observed differences between individuals. Current understanding of the cutaneous microbiota is based on sampling the outermost layers of the epidermis, while the microbiota in the remaining skin layers has not yet been fully characterized. Environmental conditions can vary drastically between the cutaneous compartments and give rise to unique communities. We demonstrate that the dermal microbiota is surprisingly similar among individuals and contains a specific subset of the epidermal microbiota. Variability in bacterial community composition decreased significantly from the epidermal to the dermal compartment but was similar among anatomic locations (hip and knee). The composition of the epidermal microbiota was more strongly affected by environmental factors than that of the dermal community. These results indicate a well-conserved dermal community that is functionally distinct from the epidermal community, challenging the current dogma. Future studies in cutaneous disorders and chronic infections may benefit by focusing on the dermal microbiota as a persistent microbial community.IMPORTANCE Human skin microbiota is thought to be unique according to the individual's lifestyle and genetic predisposition. This is true for the epidermal microbiota, while our findings demonstrate that the dermal microbiota is universal between healthy individuals. The preserved dermal microbial community is compositionally unique and functionally distinct to the specific environment in the depth of human skin. It is expected to have direct contact with the immune response of the human host, and research in the communication between host and microbiota should be targeted to this cutaneous compartment. This novel insight into specific microbial adaptation can be used advantageously in the research of chronic disorders and infections of the skin. It can enlighten the alteration between health and disease to the benefit of patients suffering from long-lasting socioeconomic illnesses.

Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection.

Staphylococcus aureus is a major human bacterial pathogen responsible for deep tissue skin infections. Recent observations have suggested that rapid, localized digestion of hyaluronic acid in the extracellular matrix (ECM) of the dermis may influence bacterial invasion and tissue inflammation. In this study we find that cell migration-inducing protein (Cemip) is the major inducible gene responsible for hyaluronan catabolism in mice. Cemip-/- mice failed to digest hyaluronan and had significantly less evidence of infection after intradermal bacterial challenge by S. aureus. Stabilization of large-molecular-weight hyaluronan enabled increased expression of cathelicidin antimicrobial peptide (Camp) that was due in part to enhanced differentiation of preadipocytes to adipocytes, as seen histologically and by increased expression of Pref1, PPARg, and Adipoq. Cemip-/- mice challenged with S. aureus also had greater IL-6 expression and neutrophil infiltration. These observations describe a mechanism for hyaluronan in the dermal ECM to regulate tissue inflammation and host antimicrobial defense.

Polyurethane-biomacromolecule combined foam dressing containing asiaticoside: fabrication, characterization and clinical efficacy for traumatic dermal wound treatment.

Polyurethane combined (PUC) foam dressings with various biomacromolecules were fabricated with the adsorption of asiaticoside and silver nanoparticles for traumatic wound treatment. Biomacromolecules had varying effects on physicochemical and mechanical properties of PU foam. With 2% incorporation, starches, high molecular weight chitosan and gelatin provided stiffer and more porous foams while carboxymethylcellulose had the highest compression strength but the lowest water vapor transmission. High water absorption was from foams with carboxymethylcellulose, alginate, hydroxypropyl methylcellulose and low molecular weight chitosan. Increasing the concentrations up to 12% had more prominent effect. However, powdery surface was noticed with poorer tensile properties that 6% incorporation was selected. FTIR spectra and DSC thermograms suggested interaction of PU formulation with biomacromolecules. EDS analysis confirmed existence of active compounds while acceptable stability was from sterilized PUC foam with alginate. On healthy volunteers, this selected foam dressing caused no skin irritation and retained moisture comparable to commercial product. In patients with traumatic dermal wounds, healing improvement with shorter wound closure time, higher reepithelialization and less pain score were from the selected foam dressing compared to standard gauze soaked with chlorhexidine. This PU-alginate combined foam dressing adsorbed with asiaticoside and silver nanoparticles proved advantages for traumatic dermal wound management.

Neutrophil Recruitment to Noninvasive MRSA at the Stratum Corneum of Human Skin Mediates Transient Colonization.

Staphylococcus aureus is a leading cause of skin and soft issue infection, but paradoxically, it also transiently, and often harmlessly, colonizes human skin. An obstacle to understanding this contradiction has been a shortage of in vivo models reproducing the unique structure and immunology of human skin. In this work, we developed a humanized model to study how healthy adult human skin responds to colonizing methicillin-resistant S. aureus (MRSA). We demonstrate the importance of the outer stratum corneum as the major site of bacterial colonization and how noninvasive MRSA adhesion to corneocytes induces a local inflammatory response in underlying skin layers. This signaling recruits neutrophils to the skin, where they control bacterial numbers, mediating transiency in colonization. This work highlights the spatiotemporal aspects of human skin colonization and demonstrates a subclinical inflammatory response to noninvasive MRSA that allows human skin to regulate the bacterial population at its outer surface.

Preparation and characterization of a gallium-loaded antimicrobial artificial dermal scaffold.

Artificial dermal scaffolds, which are made of natural or synthetic materials, can improve new blood vessel formation, cell migration and cell proliferation after being implanted into wounds, and they degrade slowly, playing an important role in dermal reconstruction and scar inhibition, finally achieving the goal of wound healing and functional reconstruction. Although these scaffolds have been widely used in clinical applications, biomaterial-associated infection is a deficiency or even a life-threatening problem that must be addressed, as it greatly affects the survival of the scaffolds. The gallium ion (Ga3+) is a novel metallic antimicrobial whose broad-spectrum antimicrobial properties against most bacteria encountered in burn wound infections have been confirmed, and it has been proposed as a promising candidate to prevent implant-associated infections. In this study, a gallium-loaded antimicrobial artificial dermal scaffold was successfully prepared by gallium ions and a collagen solution. The characterization results showed a porous structure with pore sizes ranging from 50 to 150 µm and a large porosity value of 97.4%. The enzymatic degradation rate in vitro was 19 and 28% after 12 and 24 h, respectively. In vitro antimicrobial testing revealed that the 1 h antibacterial rate against Staphylococcus aureus and Pseudomonas aeruginosa was close to 90%, which indicated its great antimicrobial activity. The results of the cytological evaluation showed slight effect on cell proliferation, with a relative growth rate (RGR) value of 80% and great cytocompatibility with cultured cells according to laser scanning confocal microscopy (LSCM) and scanning electron microscope (SEM). Furthermore, the successful prevention of wound infections in SD rats was confirmed with an in vivo antimicrobial evaluation, and the artificial dermal scaffolds also demonstrated great biocompatibility. This gallium-loaded antimicrobial artificial dermal scaffold exerted excellent antimicrobial activity and great biosafety, warranting further research for future clinical applications.

Intravital Confocal Microscopy of Dermal Innate Immune Responses to Flea-Transmitted Yersinia pestis.

The technique known as intravital microscopy (IVM), when used in conjunction with transgenic mice expressing fluorescent proteins in various cell populations, is a powerful tool with the potential to provide new insights into host-pathogen interactions in infectious disease pathogenesis in vivo. Yersinia pestis, the causative agent of plague, is typically deposited in a host's skin during feeding of an infected flea. IVM has been used to characterize the innate immune response to Y. pestis in the skin and identify differences between the responses to needle-inoculated and flea-transmitted bacteria that would have been difficult, if not impossible, to detect by other means. Here we describe techniques used to image the neutrophil response to flea-transmitted Y. pestis in the dermis of live mice using conventional confocal microscopy.

The C-type lectin receptor MGL senses N-acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid.

Staphylococcus aureus is a common skin commensal but is also associated with various skin and soft tissue pathologies. Upon invasion, S. aureus is detected by resident innate immune cells through pattern-recognition receptors (PRRs), although a comprehensive understanding of the specific molecular interactions is lacking. Recently, we demonstrated that the PRR langerin (CD207) on epidermal Langerhans cells senses the conserved ß-1,4-linked N-acetylglucosamine (GlcNAc) modification on S. aureus wall teichoic acid (WTA), thereby increasing skin inflammation. Interestingly, the S. aureus ST395 lineage as well as certain species of coagulase-negative staphylococci (CoNS) produce a structurally different WTA molecule, consisting of poly-glycerolphosphate with α-O-N-acetylgalactosamine (GalNAc) residues, which are attached by the glycosyltransferase TagN. Here, we demonstrate that S. aureus ST395 strains interact with the human Macrophage galactose-type lectin (MGL; CD301) receptor, which is expressed by dendritic cells and macrophages in the dermis. MGL bound S. aureus ST395 in a tagN- and GalNAc-dependent manner but did not interact with different tagN-positive CoNS species. However, heterologous expression of Staphylococcus lugdunensis tagN in S. aureus conferred phage infection and MGL binding, confirming the role of this CoNS enzyme as GalNAc-transferase. Functionally, the detection of GalNAc on S. aureus ST395 WTA by human monocyte-derived dendritic cells significantly enhanced cytokine production. Together, our findings highlight differential recognition of S. aureus glycoprofiles by specific human innate receptors, which may affect downstream adaptive immune responses and pathogen clearance.

Paniculitis por micobacterias atípicas tras mesoterapia / Panniculitis Due to Atypical Mycobacteria After Mesothera

No disponible

In Vivo Intradermal Delivery of Bacteria by Using Microneedle Arrays.

Infectious diseases propagated by arthropod vectors, such as tularemia, are commonly initiated via dermal infection of the skin. However, due to the technical difficulties in achieving accurate and reproducible dermal deposition, intradermal models are less commonly used. To overcome these limitations, we used microneedle arrays (MNAs), which are micron-scale polymeric structures, to temporarily disrupt the barrier function of the skin and deliver a bacterial inoculum directly to the dermis of an animal. MNAs increase reliability by eliminating leakage of the inoculum or blood from the injection site, thereby providing a biologically relevant model for arthropod-initiated disease. Here, we validate the use of MNAs as a means to induce intradermal infection using a murine model of tularemia initiated by Francisella novicida We demonstrate targeted delivery of the MNA bolus to the dermal layer of the skin, which subsequently led to innate immune cell infiltration. Additionally, F. novicida-coated MNAs were used to achieve lethality in a dose-dependent manner in C57BL/6 mice. The immune profile of infected mice mirrored that of established F. novicida infection models, consisting of markedly increased serum levels of interleukin-6 and keratinocyte chemoattractant, splenic T-cell depletion, and an increase in splenic granulocytes, together confirming that MNAs can be used to reproducibly induce tularemia-like pathogenesis in mice. When MNAs were used to immunize mice using an attenuated F. novicida mutant (F. novicida ΔlpxD1), all immunized mice survived a lethal subcutaneous challenge. Thus, MNAs can be used to effectively deliver viable bacteria in vivo and provide a novel avenue to study intradermally induced microbial diseases in animal models.

Pyrimidine synthesis inhibition enhances cutaneous defenses against antibiotic resistant bacteria through activation of NOD2 signaling.

Multidrug-resistant bacterial strains are a rapidly emerging healthcare threat; therefore it is critical to develop new therapies to combat these organisms. Prior antibacterial strategies directly target pathogen growth or viability. Host-directed strategies to increase antimicrobial defenses may be an effective alternative to antibiotics and reduce development of resistant strains. In this study, we demonstrated the efficacy of a pyrimidine synthesis inhibitor, N-phosphonacetyl-L-aspartate (PALA), to enhance clearance of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter baumannii strains by primary human dermal fibroblasts in vitro. PALA did not have a direct bactericidal effect, but enhanced cellular secretion of the antimicrobial peptides human ß-defensin 2 (HBD2) and HBD3 from fibroblasts. When tested in porcine and human skin explant models, a topical PALA formulation was efficacious to enhance MRSA, P. aeruginosa, and A. baumannii clearance. Topical PALA treatment of human skin explants also resulted in increased HBD2 and cathelicidin (LL-37) production. The antimicrobial actions of PALA required expression of nucleotide-binding, oligomerization domain 2 (NOD2), receptor-interacting serine/threonine-protein kinase 2 (RIP2), and carbamoyl phosphatase synthase II/aspartate transcarbamylase/dihydroorotase (CAD). Our results indicate that PALA may be a new option to combat multidrug-resistant bacterial infections of the skin through enhancement of an integral pathway of the cutaneous innate immune defense system.

Micelle-Coated, Hierarchically Structured Nanofibers with Dual-Release Capability for Accelerated Wound Healing and Infection Control.

Tailoring nanofibrous matrices-a material with much promise for wound healing applications-to simultaneously mitigate bacterial colonization and stimulate wound closure of infected wounds is highly desirable. To that end, a dual-releasing, multiscale system of biodegradable electrospun nanofibers coated with biocompatible micellar nanocarriers is reported. For wound healing, transforming growth factor-ß1 is incorporated into polycaprolactone/collagen (PCL/Coll) nanofibers via electrospinning and the myofibroblastic differentiation of human dermal fibroblasts is locally stimulated. To prevent infection, biocompatible nanocarriers of polypeptide-based block copolymer micelles are deposited onto the surfaces of PCL/Coll nanofibers using tannic acid as a binding partner. Micelle-modified fibrous scaffolds are favorable for wound healing, not only supporting the attachment and spreading of fibroblasts comparable to those on noncoated nanofibers, but also significantly enhancing fibroblast migration. Micellar coatings can be loaded with gentamicin or clindamycin and exhibit antibacterial activity as measured by Petrifilm and zone of inhibition assays as well as time-dependent reduction of cellular counts of Staphylococcus aureus cultures. Moreover, delivery time of antibiotic dosage is tunable through the application of a novel modular approach. Altogether, this system holds great promise as an infection-mitigating, cell-stimulating, biodegradable skin graft for wound management and tissue engineering.

Propionibacterium Acnes Persists Despite Various Skin Preparation Techniques.

PURPOSE: To investigate the efficacy of various skin preparations at eradicating Propionibacterium acnes in the dermal layer of the skin. METHODS: Twelve healthy volunteers consented to participate in this study. Each subject's upper back was prepped using 4 different techniques: an isopropyl alcohol control, chlorhexidine gluconate paint, chlorhexidine gluconate plus a mechanical scrub, and a high-concentration chlorhexidine gluconate plus a mechanical scrub. A 3-mm dermal punch biopsy specimen was obtained at each preparation site. The 4 punch biopsy specimens were cultured for 14 days to assess for P. acnes growth. A Fisher's exact test was used to compare the proportion of positive cultures in each group and across biopsy sites. A Skillings-Mack test was used to compare the degree of culture positivity between the treatment arms. RESULTS: There were no reported complications in any of our subjects. P. acnes grew in 7 of the 12 control sites, 5 of the 12 chlorhexidine gluconate sites, 6 of the 12 chlorhexidine plus mechanical scrub sites, and 6 of the 12 high-concentration chlorhexidine gluconate plus mechanical scrub sites. There were no statistically significant differences between any of the treatment arms (P = .820). CONCLUSIONS: P. acnes persisted despite a variety of clinically relevant skin antisepsis preparations and techniques. LEVEL OF EVIDENCE: Level II, prospective comparative study.

The lantibiotic gallidermin acts bactericidal against Staphylococcus epidermidis and Staphylococcus aureus and antagonizes the bacteria-induced proinflammatory responses in dermal fibroblasts.

Antimicrobial resistance needs to be tackled from new angles, and antimicrobial peptides could be future candidates for combating bacterial infections. This study aims to investigate in vitro the bactericidal effects of the lantibiotic gallidermin on Staphylococcus epidermidis and Staphylococcus aureus, possible cytotoxic effects and its impact on host-microbe interactions. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of gallidermin were determined, and cytotoxicity and proinflammatory effects of gallidermin on fibroblasts, red blood cells (RBCs) and in whole blood were investigated. Both MIC and MBC for all four tested strains of S. epidermidis was 6.25 µg/ml. Both MIC and MBC for methicillin-sensitive S. aureus was 12.5 µg/ml and for methicillin-resistant S. aureus (MRSA) 1.56 µg/ml. Gallidermin displayed no cytotoxic effects on fibroblasts, only a high dose of gallidermin induced low levels of CXCL8 and interleukin-6. Gallidermin hemolyzed less than 1% of human RBCs, and did not induce reactive oxygen species production or cell aggregation in whole blood. In cell culture, gallidermin inhibited the cytotoxic effects of the bacteria and totally suppressed the bacteria-induced release of CXCL8 and interleukin-6 from fibroblasts. We demonstrate that gallidermin, expressing low cell cytotoxicity, is a promising candidate for treating bacterial infections caused by S. epidermidis and S. aureus, especially MRSA.