IL-17 in skin infections and homeostasis.

Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.

Retrospective clinical and microbiologic analysis of metagenomic next-generation sequencing in the microbiological diagnosis of cutaneous infectious granulomas.

BACKGROUND: Cutaneous infectious granulomas (CIG) are localized and chronic skin infection caused by a variety of pathogens such as protozoans, bacteria, worms, viruses and fungi. The diagnosis of CIG is difficult because microbiological examination shows low sensitivity and the histomorphological findings of CIG caused by different pathogens are commonly difficult to be distinguished. OBJECTIVE: The objective of this study is to explore the application of mNGS in tissue sample testing for CIG cases, and to compare mNGS with traditional microbiological methods by evaluating sensitivity and specificity. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 1st, 2020, to May 31st, 2024. Specimens from CIG patients with a clinical presentation of cutaneous infection that was supported by histological examination were retrospectively enrolled. Specimens were delivered to be tested for microbiological examinations and mNGS. RESULTS: Our data show that mNGS detected Non-tuberculosis mycobacteria, Mycobacterium tuberculosis, fungi and bacteria in CIG. Compared to culture, mNGS showed a higher positive rate (80.77% vs. 57.7%) with high sensitivity rate (100%) and negative predictive value (100%). In addition, mNGS can detect more pathogens in one sample and can be used to detect variable samples including the samples of paraffin-embedded tissue with shorter detective time. Of the 21 patients who showed clinical improvement within a 30-day follow-up, eighteen had their treatments adjusted, including fifteen who continued treatment based on the results of mNGS. CONCLUSIONS: mNGS could provide a potentially rapid and effective alternative detection method for diagnosis of cutaneous infectious granulomas and mNGS results may affect the clinical prognosis resulting from enabling the patients to initiate timely treatment.

Disseminated protothecosis: Case report and review of the literature.

BACKGROUND: Human protothecosis is an uncommon infection caused by Prototheca spp that rarely infects humans. AIM: Description of a rare disease and a review of its articles. MATERIALS AND METHODS: We reported a 24-year-old man who presented with red-brown papules and plaques on the trunk's lateral side. We reviewed the literature about disseminated protothecosis and reported our experience with a patient with protothecosis between 2021 and 2023. RESULTS: Overall, 54 cases of disseminated protothecosis were evaluated, 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and three were due to Prototheca spp. We found that males were more affected (37 cases, 68.5%) than females (16 cases, 29.6%). The mean age of patients was 39.53 ± 22.48 years. However, disseminated protothecosis can affect people of any age (1-80 years). In contrast to P. wickerhamii, which causes blood, skin, brain, and gastrointestinal tract infections, P. zopfii was mainly found in the blood (7/22) and did not have a significant difference in the mortality rate (P = 0.11). DISCUSSION: Disseminated protothecosis is a rare disease in immunocompromised patients but is generally rarer in immunocompetent hosts. Several underlying disorders include immunocompromised patients, prolonged application of steroids, diabetes mellitus, malignancies, organ transplantation, AIDS, and surgeries. Amphotericin B has been the most effective agent for protothecosis and is reserved for visceral and disseminated infections. Regarding localized cutaneous types, excision or surgical debridement is used. CONCLUSION: Mulberry's appearance and appropriate cultural environments are helpful in diagnosing it.

Systemic therapy for psoriasis and the risk of cutaneous infections.

Systemic treatments are important for patients with moderate-to-severe psoriasis; however, they may occasionally cause adverse infectious events. Although the risk of severe infections with psoriatic treatments is well established, little is known about cutaneous infections. Therefore, we studied the frequency of cutaneous infections in patients with psoriasis who underwent biologic treatment. A total of 878 patients (237 females and 641 males) were analyzed in this follow-up survey conducted in 2020 and based on the Western Japan Psoriasis Registry. The observed skin phenotypes were psoriasis vulgaris (83.3%), pustular psoriasis (7.5%), and psoriatic arthritis (28.9%). The most frequently prescribed systemic drug was apremilast (11.3%), followed by ixekizumab (11.0%), risankizumab (10.9%), and secukinumab (10.4%). The incidence of cutaneous bacterial infections was 12 (1.37% of the total patients), with cellulitis being the most common (8/12, 67%). The incidence of viral infections was 11 (1.25%) including the most common, herpes zoster (9/11, 82%); and that of fungal infections was 45 (5.13%) including 33 (73%) and seven (16%) patients with trichophytosis and oral candidiasis, respectively. Multivariate analysis revealed that cutaneous bacterial infections were frequently observed in patients receiving tumor necrosis factor-α (odds raio [OR] 9.917, 95% confidence interval [CI] 2.069-47.572, p = 0.004) and interleukin (IL)-17 (OR 10.798, 95% CI 2.35-49.616, p = 0.002) inhibitor treatments. A history of otitis media and treatment with oral medications (OR 4.50, 95% CI 1.281-15.804, p = 0.019 and OR 3.80, 95% CI 1.141-12.679, p = 0.03 respectively) were associated with a higher ORs for cutaneous viral infections. Furthermore, age and use of IL-17 inhibitors were associated with elevated ORs for fungal infections. In conclusion, our study reveals that systemic therapies may increase the risk of cutaneous viral infections. Therefore, dermatologists should exercise caution in this regard.

Successful treatment of cutaneous protothecosis with fluconazole: A case report and epidemiology study of Prototheca infection in China.

BACKGROUND: Protothecosis is an infection of humans and animals caused by a rare conditionally pathogenic fungus (prototheca). It can occur in immunocompromised or normal patients. AIMS: To describe the epidemiology of prototheca infection in China. METHODS: We report a case of successful treatment of cutaneous protothecosis with fluconazole and analyzed the epidemiological characteristics, risk factors, clinical manifestations, diagnosis, treatment and prognosis of prototheca infections in China. RESULTS: We describe this case and 29 cases of prototheca infections in China. At present, Prototheca wickerhamii (Pw) infection is the most common infection in China, and single or combined itraconazole is the preferred treatment. CONCLUSIONS: These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of protothecosis in China.

Pharmacokinetics of intravenous daptomycin in Japanese pediatric patients: Pharmacokinetic comparisons supporting dosing recommendations in Japanese pediatric patients.

INTRODUCTION: The pharmacokinetics (PK) of daptomycin has not been previously characterized in Japanese pediatric patients with complicated skin and soft tissue infections (cSSTI) or bacteremia. An aim of the study includes evaluation of PK of daptomycin in Japanese pediatric patients and an appropriateness of the age-specific, weight-based dosing regimens in Japanese pediatric patients based on PK comparison with Japanese adult patients. METHODS: The phase 2 trial enrolled Japanese pediatric patients (age 1-17 years) with cSSTI (n = 14) or bacteremia (n = 4) caused by gram-positive cocci in order to evaluate safety, efficacy and PK. The Phase 3 trial in Japanese adult patients (SSTI n = 65, septicemia/right-sided infective endocarditis (RIE) n = 7) was referred to for PK comparison between adult and pediatric. Daptomycin concentrations in plasma were analyzed by reverse-phase high-performance liquid chromatography (HPLC). PK parameters were determined using non-compartmental analysis in Japanese pediatric and Japanese adult patients. The exposures in Japanese pediatric patients were graphically compared with those in Japanese adult patients. The relationship between daptomycin exposures and creatine phosphokinase (CPK) elevation was explored visually. RESULTS: Following administration of the age-specific, weight-based dosing regimens, daptomycin exposures were overlapping across age groups in pediatric patients with cSSTI with similar observations based on clearance. The distribution of individual exposure in Japanese pediatric patients was overlapping with that in Japanese adult patients. No apparent relationship between daptomycin exposures and CPK elevation in Japanese pediatric patients was observed. CONCLUSIONS: The results suggested that the age-specific, weight-based dosing regimens are considered to be appropriate in Japanese pediatric patients.

Small, Cationic Antifungal Proteins from Filamentous Fungi Inhibit Candida albicans Growth in 3D Skin Infection Models.

The emerging resistance of human-pathogenic fungi to antifungal drugs urges the development of alternative therapeutic strategies. The small, cationic antifungal proteins (AFPs) from filamentous ascomycetes represent promising candidates for next-generation antifungals. These bio-molecules need to be tested for tolerance in the host and efficacy against fungal pathogens before they can be safely applied in humans. Testing of the efficacy and possible adverse effects of new drug candidates in three-dimensional (3D) human-cell based models represents an advantageous alternative to animal experiments. In, this study, as a proof-of-principle, we demonstrate the usefulness of 3D skin infection models for screening new antifungal drug candidates for topical application. We established a cutaneous infection with the opportunistic human-pathogenic yeast Candida albicans in a commercially available 3D full-thickness (FT) skin model to test the curative potential of distinct AFPs from Penicillium chrysogenum (PAFopt, PAFB, and PAFC) and Neosartorya (Aspergillus) fischeri (NFAP2) in vitro. All tested AFPs were comparably well tolerated by the skin models. The infected 3D models exhibited reduced epidermal permeability barriers, allowing C. albicans to colonize the epidermal and dermal layers, and showed increased secretion of the pro-inflammatory cytokine IL-6 and the chemokine IL-8. AFP treatment diminished the fungal burden and penetration depth of C. albicans in the infected models. The epidermal permeability barrier was restored and the secretion of IL-8 was decreased following AFP treatment. In summary, our study proves that the tested AFPs exhibit antifungal potential against cutaneous C. albicans infection in a 3D FT skin model. IMPORTANCE Candida albicans represents one of the most prevalent opportunistic fungal pathogens, causing superficial skin and mucosal infections in humans with certain predisposing health conditions and life-threatening systemic infections in immunosuppressed patients. The emerging drug resistance of this human-pathogenic yeast and the limited number of antifungal drugs for prevention and treatment of infections urgently demands the identification of new antifungal compounds with novel mechanisms of action. Small, cationic antifungal proteins (AFPs) from filamentous fungi represent promising candidates for next-generation antifungals for topical application. These bio-molecules need to be tested for tolerance by the host and efficacy in pathogen clearance prior to being involved in clinical trials. In a proof-of-principle study, we provide evidence for the suitability of 3D human-cell based models as advantageous alternatives to animal experiments. We document the tolerance of specific AFPs and their curative efficacy against cutaneous C. albicans infection in a 3D skin model.

Características clínicas y microbiológicas de infecciones de piel y partes blandas en pacientes pediátricos de dos hospitales de Buenos Aires / Skin and soft tissue infections in pediatrics

Las infecciones de piel y partes blandas (IPPB) en niños son una de las principales causas de prescripción de antimicrobianos. El objetivo del estudio fue describir las características clínicas y microbiológicas de las IPPB ambulatorias de niños asistidos en dos hospitales zonales. Se realizó un estudio prospectivo entre el 1/11/2017 y el 1/11/2018. Se incluyeron pacientes entre 1 mes y 15 años internados en dos hospitales. Se evaluó: edad, sexo, localidad, factores predisponentes, tipo de IPPB, muestras biológicas realizadas, aislamiento microbiológico, tratamiento empírico indicado y evolución del cuadro. Se realizó antibiograma y determinación genética. Se calculó chi2, IC95, OR; α=5%. N= 94. 58,7% masculinos. 12 pacientes <1 año, 85 >1 año (promedio de edad 4 años, 1-15). El 36% de Tandil y 63,8% de Florencio Varela. El 59,6% corresponden a IPPB purulentas. Se aislaron microorganismos en un 59,6%. Los aislamientos principales: SAMR (40,4%), SAMS (7,4%), S. agalactiae (2,1%) y S. pyogenes (2,1%). El 100% de SAMR son portadores de gen mecA y SCCmec tipo IV, sin multirresistencia. No hubo diferencia estadística entre los factores de riesgo evaluados para el desarrollo de IPPB por SAMR. El 52,1% de los niños recibió tratamiento antibiótico combinado, siendo la más indicada TMS-SMX + CLI en 36 eventos. (38,3%). La evolución fue favorable: no hubo diferencia significativa entre el subgrupo que se aisló SAMR y el que no se aisló SAMR; 91,9% (34/37) y 92,6% (50/54) correspondientemente (chi2: 0,01; p= 0,97 IC95: 0,26-3,88). El principal agente etiológico fue SAMRco, debiendo adecuar los tratamientos a este microorganismo.

Skin and soft tissue infections (SSIs) in children are one of the main causes of antimicrobial prescription. The aim of the study was to describe the clinical and microbiological characteristics of outpatient SSIs in children attended in two hospitals. A prospective study was conducted between 11/1/2017 and 11/1/2018. Patients between 1 month and 15 years old, hospitalized were included. We evaluated: age, sex, locality, predisposing factors, type of IPPB, biological samples taken, microbiological isolation, empirical treatment indicated and evolution of the condition. An antibiogram and genetic determination were performed. Chi2, CI95, OR; α=5% were calculated. N= 94. 58.7% male. 12 patients <1 year, 85 >1 year (mean age 4 years, 1-15). 36% were from Tandil and 63.8% from Florencio Varela. 59.6% corresponded to purulent SSIs. The diagnostic yield was 59.6%. Main isolates: MRSA (40.4%), MSSA (7.4%), S. agalactiae (2.1%) and S. pyogenes (2.1%). 100% of MRSA carried the mecA gene and SCCmec type IV, with no multidrug resistance. There was no statistical difference between the risk factors evaluated. 52.1% of children received combined antibiotic treatment, the most indicated being TMS-SMX + CLI in 36 events. (38,3%). Evolution was favorable: there was no significant difference between the subgroup that isolated MRSA and the subgroup that did not isolate MRSA; 91.9% (34/37) and 92.6% (50/54) respectively (chi2: 0.01; p= 0.97 CI95: 0.26-3.88). The main etiological agent was MRSA, and treatments should be adapted to this microorganism

Sequence type 8 as an emerging clone of methicillin-resistant Staphylococcus aureus causing bloodstream infections in Taiwan.

Sequence type (ST) 8 has not been a common methicillin-resistant Staphylococcus aureus (MRSA) clone in Asia until recently. We aimed to determine the clinical significance and microbiological characteristics of MRSA bacteraemia (MRSAB) caused by ST8 and other endemic clones. A total of 281 non-duplicated MRSAB were identified in a medical centre between 2016 and 2018. Sequencing of target genes was performed to determine ST and to confirm ST8 belonging to USA300. Antimicrobial susceptibility testing was performing by using Sensititre standard panel. In total, ST8 accounted for 18.5% of MRSAB ranking after ST239 (31.0%) and ST59 (23.5%). However, it increased to become the most prevalent clone finally. All ST8 isolates belonged to spa clonal complex008, and carried SCCmec IV/IVa, PVL and ACME genes, indicating USA300. ST8/USA300 isolates were highly susceptible to non-ß-lactams antibiotics, except fluoroquinolone and erythromycin. ST8/USA300 MRSAB is commonly developed in community settings with either healthcare risks or not (71.2%). Compared to other STs MRSAB, ST8/USA300 MRSAB patients had more diabetes mellitus (50.0%), more admitted from long-term care facility residents (25.0%), had more skin ad soft tissue infection as primary focus (25.0%), and had fewer vascular devices (26.9%) at MRSAB onset. On multivariable analysis, isolates with vancomycin MIC were significantly associated with mortality in the dose-response relationship, rather than STs. This report depicts the clinical features of ST8/USA300 MRSAB and clonal shift from prior endemic clones to ST8/USA300. Our data strongly support long-term surveillance to ascertain whether ST8/USA300 will successfully disseminate and demonstrate its pathogenicity on clinical outcomes.

Enfrentamiento de las infecciones de piel en el adulto / Managing adult skin infections

En la actualidad, las infecciones de piel y partes blandas forman parte de un alto porcentaje de las consultas en salud. Estas van desde infecciones leves, donde el manejo se realiza con tratamiento tópico, hasta aquellas con severo compromiso sistémico, requiriendo terapia antibiótica sistémica e incluso el desbridaje quirúrgico. En general, son producto de un desbalance entre los mecanismos de defensa de la barrera cutánea y los factores de virulencia y patogenicidad de los microorganismos que la afectan. Se pueden clasificar según distintos criterios, como por ejemplo, profundidad, gravedad, microorganismos involucrados y si estas son purulentas o no. El reconocer estas entidades clínicas es de suma importancia para llevar a cabo un adecuado tratamiento en los pacientes que presentan estas afecciones, ya que los diagnósticos erróneos llevan a las múltiples consultas con el consiguiente aumento de costos asociados en atención en salud.

Currently, skin and soft tissue infections are part of a high percentage of health consultations. These range from mild infections, where management is performed with topical treatment, to those with severe systemic compromise requiring systemic antibiotic therapy and even surgical debridement. In general, they are the product of an imbalance between the defense mechanisms of the skin barrier and the virulence and pathogenicity factors of the microorganisms that affect it, which can vary from bacterial, viral, fungal and parasites agents. Skin and soft tissue infections can be classified according to different criteria, such as depth, severity, microorganisms involved and whether they are purulent or not. Recognizing these clinical entities is of utmost importance to carry out adequate treatment in patients with these conditions, since erroneous diagnoses lead to multiple consultations with the consequent increase in costs associated with health care

Antimicrobial and cytotoxic activity of green synthesis silver nanoparticles targeting skin and soft tissue infectious agents.

Combining traditional medicine with nanotechnology therefore opens the door to innovative strategies for treating skin and soft tissue infections (SSTIs) and also contributes to the fight against the rise of antimicrobial resistance. Acanthospermum australe (Loefl.) Kuntze is a medicinal plant used by indigenous peoples in northeastern Argentina to treat SSTIs. Spherical and stable silver nanoparticles (AgNPs) of 14 ± 2 nm were synthesized from the aqueous extract of A. australe and silver nitrate. The antimicrobial activity against main species causing SSTIs and cytotoxicity on peripheral blood mononuclear cells of AgNP solution and its synthesis components were evaluated. Compared to its synthesis components, AgNP solution showed greater antimicrobial activity and lower cytotoxicity. The antimicrobial activity of AgNPs was due to the silver and not to the metabolites of the aqueous extract present on the surface of the nanoparticles. The plant extract played an important role in the formation of stable AgNPs and acted as a modulator of cytotoxic and immune responses.

Staphylococcus aureus impairs dermal fibroblast functions with deleterious effects on wound healing.

Chronic wounds are a major disease burden worldwide. The breach of the epithelial barrier facilitates transition of skin commensals to invasive facultative pathogens. Therefore, we investigated the potential effects of Staphylococcus aureus (SA) on dermal fibroblasts as key cells for tissue repair. In co-culture systems combining live or heat-killed SA with dermal fibroblasts derived from the BJ-5ta cell line, healthy individuals, and patients with systemic sclerosis, we assessed tissue repair including pro-inflammatory cytokines, matrix metalloproteases (MMPs), myofibroblast functions, and host defense responses. Only live SA induced the upregulation of IL-1ß/-6/-8 and MMP1/3 as co-factors of tissue degradation. Additionally, the increased cell death reduced collagen production, proliferation, migration, and contractility, prerequisite mechanisms for wound closure. Intracellular SA triggered inflammatory and type I IFN responses via intracellular dsDNA sensor molecules and MyD88 and STING signaling pathways. In conclusion, live SA affected various key tissue repair functions of dermal fibroblasts from different sources to a similar extent. Thus, SA infection of dermal fibroblasts should be taken into account for future wound management strategies.

Cellulitis: A Review of Pathogenesis, Diagnosis, and Management.

Cellulitis is a common skin infection resulting in increasing hospitalizations and health care costs. There is no gold standard diagnostic test, making cellulitis a potentially challenging condition to distinguish from other mimickers. Physical examination typically demonstrates poorly demarcated unilateral erythema with warmth and tenderness. Thorough history and clinical examination can narrow the differential diagnosis of cellulitis and minimize unnecessary hospitalization. Antibiotic selection is determined by patient history and risk factors, severity of clinical presentation, and the most likely microbial culprit.

Common Cutaneous Infections: Patient Presentation, Clinical Course, and Treatment Options.

This evidence-based review highlights cutaneous infections of bacterial, viral, and fungal origin that are frequently encountered by clinicians in all fields of practice. With a focus on treatment options and management, the scope of this article is to serve as a reference for physicians, regardless of field of specialty, as they encounter these pathogens in clinical practice.

Expression of epidermal antimicrobial peptides is increased in tinea pedis.

BACKGROUND: Tinea pedis is often chronic or recurrent, but not all individuals are equally susceptible to this infection. Dermatophytes are able to induce the expression of antimicrobial peptides and proteins (AMPs) in human keratinocytes and certain AMPs can inhibit the growth of dermatophytes. OBJECTIVE: The focus of this study was to analyse the secretion of relevant AMPs, especially RNase 7, human beta-defensin-2 (hBD-2) and the S-100 protein psoriasin (S100A7), in patients with confirmed tinea pedis. METHODS: To verify the diagnosis, skin scales were obtained from all patients (n = 13) and the dermatophytes were identified by potassium hydroxide mount, culture and molecular analysis. To determine the AMP concentrations, the lesional skin area of the foot was rinsed with a buffer that was subsequently analysed by ELISA. The corresponding area of the other unaffected foot as well as defined healthy skin areas of the forearm and forehead and samples from age and gender-matched healthy volunteers served as controls. RESULTS: In tinea pedis patients the AMP concentrations were higher in lesional skin than in non-lesional skin and in healthy skin of controls. In particular, concentrations of hBD-2 and psoriasin were significantly elevated. CONCLUSIONS: The induction of AMPs in tinea pedis might be triggered directly by the dermatophytes; furthermore, attendant inflammation and/or differentiation processes may play a role. Our results indicate that there is no defect in the constitutive expression and induction of the analysed AMPs by dermatophytes in the epidermis of affected patients. However, it is not known why the elevated AMP concentrations fail to efficiently combat dermatophyte growth.

Wounds and Skin and Soft Tissue Infections in People Who Inject Drugs and the Utility of Syringe Service Programs in Their Management.

Significance: Opioid use disorder and transition to injection drug use (IDU) are an urgent, nationwide public health crisis. Wounds and skin and soft tissue infections (SSTIs) are common complications of IDU that disproportionately affect people who inject drugs (PWID) and are a major source of morbidity and mortality for this population. Critical Issues: Injections in a nonsterile environment and reusing or sharing needles facilitates bacterial inoculation, with subsequent risk of serious complications such as sepsis, gangrene, amputation, and death. PWID are susceptible to infections with a wide spectrum of organisms beyond common culprits of SSTI, including Clostridium and Bacillus spp., as well as Candida. Recent Advances: Syringe services programs (SSPs) are cost-effective and successful in reducing harms associated with IDU. SSPs provide new equipment to PWID and aid in discarding used equipment. SSPs aim to reduce the risks of unhygienic injecting practices, which are associated with transmission of infections and blood-borne pathogens. Future Directions: Concurrently run SSPs and wound care clinics are uniquely positioned to facilitate care to PWID. Providing new, sterile equipment as well as early wound care intervention can reduce morbidity and mortality as well as health care expenditures by reducing the number of SSTI and injection-related wounds that require hospital admission. Establishment of wound care clinics as part of an SSP represents an untapped potential to reduce harm.

Frequency and yield of blood cultures for observation patients with skin and soft tissue infections.

OBJECTIVES: 1) To measure frequency and yield of blood cultures obtained for observation status adult patients with skin and soft tissue infection (SSTI), 2) describe how often blood cultures were performed according to Infectious Diseases Society of America (IDSA) SSTI guideline indications, 3) identify proportion of patients meeting Center for Medicare Services (CMS) sepsis criteria. DESIGN: Retrospective cohort. SETTING: Tertiary academic center. PATIENTS: Consecutive adult observation status patients hospitalized with SSTI between July 2017 and July 2018. METHODS: We measured the proportion and results of blood cultures obtained among the study cohort and proportion of obtained cultures that satisfied IDSA indications. RESULTS: We identified 132 observation status patients with SSTI during the study period; 67 (50.8%) had blood cultures drawn. Only 14 (10.6%) patients met IDSA indications for culture; 51 (38.%) met Center for Medicare Services definition for sepsis. We identified two (3.0%) cases of bacteremia and two (3.0%) cases of skin bacteria contamination. In multivariable analysis, only temperature > 38 °C (OR 3.84, 95%CI 1.09-13.60) and white race (OR 2.71, 95%CI 1.21-6.20) were associated with blood culture obtainment; neither meeting IDSA SSTI guideline indications nor meeting CMS sepsis criteria was associated with culture. CONCLUSIONS: Among observation status patients with SSTI, over half had blood cultures drawn, though 10% satisfied guideline indications for culture. The proportion of cultures with bacterial growth was low and yielded as many skin contaminants as cases of bacteremia. Our study highlights the need for further quality improvement efforts to reduce unnecessary blood cultures in routine SSTI cases.

Longitudinal whole-genome based comparison of carriage and infection associated Staphylococcus aureus in northern Australian dialysis clinics.

BACKGROUND: The study objective was to reveal reservoirs potentially leading to Staphylococcus aureus infections in haemodialysis clinic clients in the tropical north of the Australian Northern Territory (NT). This client population are primarily Aboriginal Australians who have a greater burden of ill health than other Australians. Reservoir identification will enhance infection control in this client group, including informing potential S. aureus decolonisation strategies. METHODS AND FINDINGS: The study participants were 83 clients of four haemodialysis clinics in the Darwin region of the NT, and 46 clinical staff and researchers who had contact with the clinic clients. The study design was longitudinal, encompassing swabbing of anatomical sites at two month intervals to yield carriage isolates, and also progressive collection of infection isolates. Swab sampling was performed for all participants, and infection isolates collected for dialysis clients only. Analysis was based on the comparison of 139 carriage isolates and 27 infection isolates using whole genome sequencing. Genome comparisons were based on of 20,651 genome-wide orthologous SNPs, presence/absence of the mecA and pvl genes, and inferred multilocus sequence type and clonal complex. Pairs of genomes meeting the definition of "not discriminated" were classed as defining potential transmission events. The primary outcome was instances of potential transmission between a carriage site other than a skin lesion and an infection site, in the same individual. Three such instances were identified. Two involved ST762 (CC1) PVL- MRSA, and one instance ST121 PVL+ MSSA. Three additional instances were identified where the carriage strains were derived from skin lesions. Also identified were six instances of potential transmission of a carriage strains between participants, including transmission of strains between dialysis clients and staff/researchers, and one potential transmission of a clinical strain between participants. There were frequent occurrences of longitudinal persistence of carriage strains in individual participants, and two examples of the same strain causing infection in the same participants at different times. Strains associated with infections and skin lesions were enriched for PVL and mecA in comparison to strains associated with long term carriage. CONCLUSIONS: This study indicated that strains differ with respect to propensity to stably colonise sites such as the nose, and cause skin infections. PVL+ strains were associated with infection and skin lesions and were almost absent from the carriage sites. PVL- MRSA (mainly CC1) strains were associated with infection and also with potential transmission events involving carriage sites, while PVL- MSSA were frequently observed to stably colonise individuals without causing infection, and to be rarely transmitted. Current clinical guidelines for dialysis patients suggest MRSA decolonisation. Implementation in this client group may impact infections by PVL- MRSA, but may have little effect on infection by PVL+ strains. In this study, the PVL+ strains were predominant causes of infection but rarely colonised typical carriage sites such as the nose, and in the case of ST121, were MSSA. The important reservoirs for infection by PVL+ strains appeared to be prior infections.

Approach to the Patient with a Skin and Soft Tissue Infection.

The diagnosis of a skin and soft tissue infection (SSTI) requires careful attention to a patient's history, physical examination, and diagnostic test results. We review for many bacterial, viral, fungal, and parasitic pathogens that cause SSTIs the clues for reaching a diagnosis, including reported past medical history, hobbies and behaviors, travel, insect bites, exposure to other people and to animals, environmental exposures to water, soil, or sand, as well as the anatomic site of skin lesions, their morphology on examination, and their evolution over time. Laboratory and radiographic tests are discussed that may be used to confirm a specific diagnosis.

Exogenous factors in the pathogenesis of atopic dermatitis: Irritants and cutaneous infections.

Atopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and healthcare costs. The pathogenesis of AD is complicated and multifactorial. Although the aetiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections.