Basophil-derived IL-4 promotes cutaneous Staphylococcus aureus infection.

Superficial cutaneous Staphylococcus aureus (S. aureus) infection in humans can lead to soft tissue infection, an important cause of morbidity and mortality. IL-17A production by skin TCRγδ+ cells in response to IL-1 and IL-23 produced by epithelial and immune cells is important for restraining S. aureus skin infection. How S. aureus evades this cutaneous innate immune response to establish infection is not clear. Here we show that mechanical injury of mouse skin by tape stripping predisposed mice to superficial skin infection with S. aureus. Topical application of S. aureus to tape-stripped skin caused cutaneous influx of basophils and increased Il4 expression. This basophil-derived IL-4 inhibited cutaneous IL-17A production by TCRγδ+ cells and promoted S. aureus infection of tape-stripped skin. We demonstrate that IL-4 acted on multiple checkpoints that suppress the cutaneous IL-17A response. It reduced Il1 and Il23 expression by keratinocytes, inhibited IL-1+IL-23-driven IL-17A production by TCRγδ+ cells, and impaired IL-17A-driven induction of neutrophil-attracting chemokines by keratinocytes. IL-4 receptor blockade is shown to promote Il17a expression and enhance bacterial clearance in tape-stripped mouse skin exposed to S. aureus, suggesting that it could serve as a therapeutic approach to prevent skin and soft tissue infection.

Congenital erythropoietic porphyria (Gunther disease) - long-term follow up of a case and review.

Patients with the rare genodermatosis congenitalerythropoietic porphyria (CEP, Gunther disease)develop erosions and scarring on sun-exposedsites caused by phototoxin mediated damage.Compromised skin barrier function places patientsat higher risk of infection and long term sequelaeinclude scarring. We report a long term follow up ofa 60 year old patient born with CEP and provide anextensive literature review of CEP including recentupdates on potential management options. Multiplepatient interviews and collection of biochemistry datawere conducted for the case discussion. All Australianpathology laboratories in each state performingporphyria testing were surveyed in mid 2015 to verifyexistence of other cases of CEP in Australia with onlyone case of true congenital porphyria identifiedand one adult onset case. Congenital erythropoieticporphyria is a rare condition with no cure currentlyavailable. It is important to diagnose patients earlyto prevent and minimize complications such asscarring and secondary infection, provide longterm skin checks, and advise patients about lifestylemodification.

Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation.

Mast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human Staphylococcus aureus-infected skin abscess specimens, respectively, but they were produced in vitro by all clinical isolates. The results suggest that Hld and PSM-α1 produced in vivo during S. aureus skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of S. aureus via the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of S. aureus strains with a functional agr system.

CA-MRSA Decolonization Strategies: Do They Reduce Recurrence Rate?

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus commonly presents as a skin and soft tissue infection. Recurrence of the infection is common even after incision and drainage of the affected area. OBJECTIVE: This Evidence-Based Report Card reviews whether decolonization strategies will reduce the rate of methicillin-resistant Staphylococcus aureus skin and soft tissue infection (MRSA-SSTI) recurrence or colonization in patients with a history of MRSA-SSTI. METHODS: A systematic review of the literature was conducted from 1987 to the present day. The studies that were evaluated included individuals with recurrent skin and soft tissue infections that used decolonization procedures to decrease recurrence. The literature search generated 754 articles. Of these, 288 articles were eliminated due to duplication. Of the 466 remaining citations, 372 were not relevant. Of the remaining 94 full-text articles, 12 met the inclusion criteria. These studies were then reviewed and findings synthesized. FINDINGS: Four studies found topical decolonization procedures were effective in reducing colonization rates. Of the studies that used combination decolonization therapy, 3 of 4 studies showed a decrease in colonization rate. Despite successful decolonization, the rate of SSTI recurrence did not decrease. Two studies that showed a decrease in SSTI recurrence utilized different study parameters. In one study, the decolonization regimen was completed monthly over 1 year. The other study treated family members in addition to the affected individual. Currently, there is insufficient evidence to support the routine use of topical or systemic decolonization regimens to decrease recurrent SSTIs in individuals with a history of MRSA-SSTI. CONCLUSION: The focus of decolonization should be focused on the prevention and spread of infection. Hygiene education should be provided to patients, household members, and close contacts to reduce infection rates.

Staphylococcus lugdunensis abscesses complicating molluscum contagiosum in two children.

We report the occurrence of Staphylococcus lugdunensis abscesses in two girls with molluscum contagiosum who both required surgical intervention under general anaesthesia. S. lugdunensis is a coagulase-negative Staphylococcus recently recognized as an emerging human pathogen. Because of its ubiquitous nature and the high prevalence of molluscum contagiosum in children, it is likely that this as yet unreported association may be underestimated, thus raising the question as to whether bacterial culture of superinfected mollusca should be obtained more often.

Intravital two-photon microscopy of host-pathogen interactions in a mouse model of Staphylococcus aureus skin abscess formation.

Staphylococcus (S.) aureus is a frequent cause of severe skin infections. The ability to control the infection is largely dependent on the rapid recruitment of neutrophils (PMN). To gain more insight into the dynamics of PMN migration and host-pathogen interactions in vivo, we used intravital two-photon (2-P) microscopy to visualize S. aureus skin infections in the mouse. Reporter S. aureus strains expressing fluorescent proteins were developed, which allowed for detection of the bacteria in vivo. By employing LysM-EGFP mice to visualize PMN, we observed the rapid appearance of PMN in the extravascular space of the dermis and their directed movement towards the focus of infection, which led to the delineation of an abscess within 1 day. Moreover, tracking of transferred labelled bone-marrow neutrophils showed that PMN localization to the site of infection is dependent on the presence of G-protein-coupled receptors on the PMN, whereas Interleukin-1 receptor was required on host cells other than PMN. Furthermore, the S. aureus complement inhibitor Ecb could block PMN accumulation at thesite of infection. Our results establish that 2-P microscopy is a powerful tool to investigate the orchestration of the immune cells, S. aureus location and gene expression in vivo on a single cell level.

Combined antibiotic/corticosteroid cream in the empirical treatment of moderate to severe eczema: friend or foe?

BACKGROUND: Eczema is a common atopic disease associated with pruritus, sleep disturbance, and impaired quality of life. Staphylococcus aureus colonization/infection is important in its pathophysiology. AIM: To evaluate the prevalence of S aureus colonization/infection and the efficacy and acceptability of a combined antibiotic/corticosteroid cream in the empirical treatment of eczema. METHODS: Consecutive patients with moderate to severe eczema were recruited. Swab and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORAD) and quality of life (Children's Dermatology Life Quality Index, CDLQI), skin hydration (SH), and transepidermal water loss (TEWL) were obtained prior to and following a two week twice-daily course of treatment with a fucidin/corticosteroid cream. General acceptability of treatment (GAT) was documented at completion. RESULTS: Thirty-five patients (63% males; mean age 13.5, standard deviation 3.6 years; with 21 moderate and 14 severe disease) were recruited. At start, S aureus was isolated from the right antecubital fossa and the worst affected areas in 66% and 71% of these patients, respectively. At completion, S aureus was isolated in 23% and 40% at the antecubital fossae and worst affected areas (P=0.001 and P=0.003, respectively). No methicillin-resistant S aureus was isolated in this series, but the percentage of fucidin-resistant S aureus increased from 8% to 58% (P<0.001). Disease severity and quality of life were significantly improved (pre-Objective SCORAD and post-Objective SCORAD were 38.4±13.7 and 29.7±14.2, P<0.001; pre-CDLQI and post-CDLQI were 9.4±5.2 and 7.1±4.8, P<0.001). At the right antecubital fossa, skin hydration improved from 30.8±14.2 to 36.7±15.2 (P=0.015); and TEWL from 10.7±2.3 to 9.4±2.2 (P<0.001). Eighty percent of patients found the treatment good or very good, and only one (3%) patient found it unacceptable. CONCLUSIONS: The most prevalent organism in moderate to severe eczema was S aureus. Usage of the combined fucidin/corticosteroid cream is convenient and associated with a reduction in disease severity, improvement in quality of life, SH, and TEWL, but caution has to be taken with emergence of fucidin-resistant S aureus.

Low-temperature plasma--a prospective microbicidal tool.

The effects of low-temperature plasma treatment on microorganisms typically related to skin diseases are studied qualitatively by the inhibition of growth and viability assays to evaluate the potential for classifying as a prospective antiseptic agent. A variety of microorganisms enveloping gram- negative and gram-positive bacteria as well as one genus of yeast and fungus each were exposed to plasma in vitro. In a comparative approach, two power supplies, both of which produce high voltage pulses yet at different temporal characteristics, are applied for the growth study. While operation with both devices led to growth inhibition of all microbes, the results indicate a superior antimicrobial efficacy for high voltage pulse lengths in the nanosecond scale. Fluorescence assays reveal the efficacy of nanosecond-pulse driven plasma in reducing germ viability. Furthermore, the technical background for patents related to low-temperature plasma technology in the field of plasma medicine is discussed.

Now is the time for tissue viability.

Tissue viability nurses (TVNs) have always been interested in pressure ulcers. Many found our way into the specialism because of this interest and passion. We have always believed most of them could be prevented and our desire, our goal has been to prevent all avoidable pressure ulcers.

Similar superantigen gene profiles and superantigen activity in norwegian isolates of invasive and non-invasive group a streptococci.

Group A streptococcus (GAS) harbours several virulence factors, including M protein (coded by the emm gene) and superantigens (SAgs). SAgs are extracellular toxins that directly activate the immune system by cross-binding to the HLA class II molecule and T cell receptor (TCR), thereby causing activation of up to 30% of the T cells and subsequent massive secretion of cytokines. Forty-eight GAS strains isolated from patients at Norwegian hospitals between 1988 and 2004 were included in this study. Of these, 24 were invasive streptococcal toxic shock syndrome (STSS) or necrotizing fasciitis (NF) isolates and 24 were non-invasive pharyngitis isolates, matched for having the same T-type and year of isolation as the invasive isolates. The isolates were characterized by emm sequence typing, multilocus sequence typing (MLST) and SAg gene profiles. A correlation between T-type, emm type, sequence type and SAg gene profile was revealed. No difference between invasive and non-invasive isolates regarding serotype or genotype was demonstrated. Selected invasive and non-invasive isolates with identical SAg gene profiles were analysed for SAg activity in bacterial growth culture media with and without human cell culture media added. A human T cell proliferation assay was used as measurement for SAg activity and simultaneously we also measured the cytokine content in normal human peripheral blood leucocyte cell culture media. The results revealed that invasive and non-invasive isolates did not differ significantly in SAg activity as it is present in semipurified bacterial culture medium.

Effectiveness of gentian violet and similar products commonly used to treat pyodermas.

The term pyoderma encompasses a variety of distinct entities including impetigo (bullous and nonbullous), erysipelas, cellulitis, folliculitis, and staphylococcal scalded skin syndrome. Treatment of pyodermas centers around wound care and appropriate antibiotic selection. Triphenylmethane dyes, such as gentian violet, represent a unique group of compounds that act as antiseptics and have shown clinical efficacy as antibiotics in a variety of pyodermas, including those secondary to methicillin-resistant Staphylococcus aureus. Given their low cost, ease of application, and favorable side effect profile, triphenylmethanes must be considered legitimate treatment options for pyodermas, particularly in the face of continued and emerging bacterial resistance.

Non-invasive assessment of healing of bacteria infected and uninfected wounds using optical coherence tomography.

BACKGROUND/PURPOSE: Bacterial infection is one of the main predisposing factors for the delay in wound healing. To facilitate a timely decision for correct therapy, it is important to accurately monitor the morphological changes in the infected wounds using noninvasive tools. In the present study, we have explored the use of optical coherence tomography (OCT) for monitoring the healing of superficial wounds infected with Staphylococcus aureus in mice under in vitro and in vivo conditions and studied the changes in collagen birefringence in the infected wounds. METHODS: The tape stripping method was used for generating superficial skin wounds in mice and wounds were infected with S. aureus. For in vitro studies, infected and uninfected wound tissues were resected, back scattered intensity and birefringence changes in collagen during wound healing were studied on the 2, 4 and 10th day of postinfection using polarization-sensitive (PS) OCT and images were compared with histology. Real-time OCT was used for studying the kinetics of healing of infected wounds under in vivo conditions. RESULTS: From the PS-OCT images, different phases of wound healing such as inflammation, reepithelialization and collagen remodeling could be identified. The edematic regions appeared prominent in infected wounds. Compared with uninfected wounds, reepithelization and collagen remodeling phases of wound healing were delayed significantly in the infected wounds. These changes were comparable with the different stages of wound healing observed under in vivo conditions. CONCLUSION: OCT imaging can provide a rapid assessment of the morphological changes associated with bacteria-infected and uninfected wounds and thereby aid in timely treatment planning.

Investigational and unproven therapies in atopic dermatitis.

Atopic dermatitis can be a challenging disease to treat, often having a chronic or relapsing course. For patients with moderate to severe disease, it can result in significant morbidity and affect quality of life of patients or families. Current treatment can be associated with side effects or patient and caregiver concerns about use. Recent advances in the understanding of barrier defects and innate and adaptive immune systemic abnormalities in atopic dermatitis have provided potential new targets for therapeutic intervention. These advances include antimicrobial peptides, antistaphylococcal toxin strategies, Th2 cytokine inhibitors, and modulation of pruritus at the neuromediator level.

Staphylococcus aureus positive skin infections and international travel.

Staphylococcus aureus is a frequent cause of purulent skin infections in travellers returning from the tropics and subtropics. This review gives an account of the current knowledge on travel-related, S. aureus positive skin infections with a focus on recent findings on both bacterial pathogenicity and mechanisms of innate defence. In particular, the potential role of community-acquired methicillin-resistance, Panton-Valentine leukocidin as well as antimicrobial peptides in the evolution of this type of infection are discussed. Moreover, conflicting findings for a possible association of travel and migration with the global emergence of community-acquired methicillin-resistant S. aureus infections are summarised. This review highlights areas of uncertainty that require further investigation.

Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

PURPOSE: Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. METHODS: We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). RESULTS: In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. CONCLUSIONS: We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

Presence of genes encoding the panton-valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin-resistant Staphylococcus aureus: results of a multinational trial.

The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

Abnormal skin barrier in the etiopathogenesis of atopic dermatitis.

PURPOSE OF REVIEW: Many recent studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the pathogenesis of atopic dermatitis. Accordingly, current therapy has been largely directed towards ameliorating Th2-mediated inflammation and/or pruritus. We will review here emerging evidence that the inflammation in atopic dermatitis results from inherited and acquired insults to the barrier and the therapeutic implications of this new paradigm. RECENT FINDINGS: Recent molecular genetic studies have shown a strong association between mutations in FILAGGRIN and atopic dermatitis, particularly in Northern Europeans. But additional acquired stressors to the barrier are required to initiate inflammation. Sustained hapten access through a defective barrier stimulates a Th1 --> Th2 shift in immunophenotype, which in turn further aggravates the barrier. Secondary Staphylococcus aureus colonization not only amplifies inflammation but also further stresses the barrier in atopic dermatitis. SUMMARY: These results suggest a new 'outside-to-inside, back to outside' paradigm for the pathogenesis of atopic dermatitis. This new concept is providing impetus for the development of new categories of 'barrier repair' therapy.