Local Skin Infection Research Articles

Risk Factors and Outcomes of Nocardiosis in Hematopoietic Stem Cell Transplantation Recipients

Nocardiosis occurs in up to 1.7% of hematopoietic stem cell transplantation (HSCT) recipients. Risk factors for its development and subsequent outcomes have been incompletely studied. The present study evaluated risk factors for nocardiosis in HSCT recipients and an association with 12-month mortality following Nocardia infection. We performed a nested case-control study of HSCT recipients at 3 transplantation centers between 2011 and 2021. Allogeneic HSCT recipients were matched 1:4 to controls based on age, sex, date of transplantation, and transplantation site. Because of theorized differences in the risk for nocardiosis between allogeneic HSCT recipients and autologous HSCT recipients and a low number of infected autologous HSCT recipients, only allogeneic HSCT recipients were matched to controls. Associations with nocardiosis in the allogeneic group were assessed by multivariable conditional logistic regression. Outcomes of all HSCT recipients with nocardiosis included 12-month mortality and post-treatment recurrence. Twenty-seven HSCT recipients were diagnosed with nocardiosis, including 20 allogeneic HSCT recipients and 7 autologous HSCT recipients. Twenty (74.1%) had localized pulmonary infection, 4 (14.8%) had disseminated infection, and 3 (11.1%) had localized skin infection. The allogeneic recipients were diagnosed at a median of 12.2 months after transplantation, compared with 41 months for the autologous recipients. All autologous HSCT recipients had alternative reasons for ongoing immunosuppression at diagnosis, most frequently therapy for relapsed hematologic disease. No infected patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In multivariable analysis of 20 allogeneic patients and 80 matched controls, graft-versus-host disease (GVHD) requiring current immunosuppression and lack of prophylaxis were associated with nocardiosis. Nocardiosis was significantly associated with subsequent mortality, with a 12-month mortality rate of 29.6%; however, no patients who completed treatment experienced Nocardia recurrence. OUR DATA INDICATE THAT: intensified immunosuppression following allogeneic HSCT, such as treatment for GVHD, is associated with the development of nocardiosis. Nocardiosis occurs more distantly from transplantation in autologous recipients, possibly driven by therapy for relapsed hematologic disease. No patients receiving TMP-SMX prophylaxis developed nocardiosis. Nocardia infection is associated with high mortality, and further strategies for prevention and treatment are needed.

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.

Global variation in skin injures and skincare practices in extremely preterm infants

BackgroundGlobally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them.MethodsA web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions.ResultsResponses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45–0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45–0.96; local skin infections: OR = 0.41, 95% CI = 0.26–0.65; chemical burns: OR = 0.46, 95% CI = 0.26–0.83; thermal burns: OR = 0.51, 95% CI = 0.27–0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33–0.67; pressure: aOR = 0.51, 95% CI = 0.34–0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51–0.99; perineal: aOR = 0.52, 95% CI = 0.36–0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed.ConclusionsSkin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

Novel Feleucin-K3-Derived Peptides Modified with Sulfono-γ-AA Building Blocks Targeting Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus Infections.

The prevalence of multidrug-resistant bacterial infections has led to dramatically increased morbidity and mortality. Antimicrobial peptides (AMPs) have great potential as new therapeutic agents to reverse this dangerous trend. Herein, a series of novel AMP Feleucin-K3 analogues modified with unnatural peptidomimetic sulfono-γ-AA building blocks were designed and synthesized. The structure-activity, structure-toxicity, and structure-stability relationships were investigated to discover the optimal antimicrobial candidates. Among them, K122 exhibited potent and broad-spectrum antimicrobial activity and high selectivity. K122 had a rapid bactericidal effect and a low tendency to induce resistance. Surprisingly, K122 showed excellent effectiveness against bacterial pneumonia. For biofilm and local skin infections, K122 significantly decreased the bacterial load and improved tissue injury at a dose of only 0.25 mg/kg, which was 160 times lower than the concentration deemed to be safe for local dermal applications. In summary, K122 is an outstanding candidate for the treatment of multidrug-resistant bacteria and biofilm infections.

Biofilm formation, multidrug-resistance and clinical infections of Staphylococcus haemolyticus: A brief review

Coagulase-negative staphylococci (CoNS) have been associated with a range of human health issues such as medical device-related infection, localized skin infection, or direct infection, are recognized as comprising the main part of human normal microbiota and associated with severe and intensive infections, causing infections in humans, especially immunocompromised patients and neonates. S. haemolyticus is, after Staphylococcus epidermidis, the second most frequently isolated CoNS from clinical cases, notably from blood infections, including sepsis. The most important factor might be the ability to acquire multiresistance against available antimicrobial agents, even glycopeptides. It is widespread in hospitals and among medical staff, resulting in being an emerging microbe causing nosocomial infections. This review discuss aspects of S. haemolyticus bloodstream infections associated, virulence factors, and the ability of biofilm formation on medical devices surfaces. The great adaptability and the ability to survive in the hospital environment, especially on medical devices, S. haemolyticus becomes a crucial factor in nosocomial infections caused by multiresistant strains.

Tunneled Uncuffed Pigtail Drainage Catheter Placement in Patients with Refractory Ascites or Pleural Effusion: A Single-Center Experience.

No evidence exists to support the use of tunneled non-cuffed pigtail drainage catheters in patients with refractory ascites or pleural effusion. The purpose of this study was to determine the feasibility of non-cuffed tunneled pigtail drainage catheters in patients with refractory ascites or pleural effusions. Between October 5, 2020 and May 25, 2021, 34 pigtail catheters were implanted in 27 patients (17 males, 10 females; average age: 65.66 ± 12.04years) under either ultrasound or computed-tomography guidance (19 catheters for ascites, 15 catheters for pleural effusion). Twenty-eight catheters (82.35%) were implanted for malignant etiologies, and 6 catheters (17.65%) were implanted for benign etiologies. The catheters (size: 8-14 French) were implanted through a subcutaneous tunnel. Complication rate and factors related to complications were analyzed. Catheter lifetime was analyzed with Kaplan-Meier method. Patency ranged from 3 to 211days. None of the patients experienced a major complication (e.g., peritonitis and empyema). Meanwhile, 8 minor complications were observed including 3 catheter occlusion, 3 ascites leakage, 1 peri-catheter local skin infection, 1 peri-catheter local skin reaction. None of the etiologies were related to the catheter complications. However, the 8-F catheter was associated with a significantly higher complication rate (odds = 5.5, p = 0.044). The estimated mean [CI] dwelling time of a catheter was 59.18 [32.97, 85.39] days. Image-guided insertion of tunneled peritoneal or pleural pigtail external drainage catheters achieved with a 100% technical success rate and resulted in an acceptable complication rate and catheter lifetime for the management of refractory ascites or pleural effusion.

Detection of role the enzyme adenosine deaminase in leishmaniasis as biomarkers during of infection

Abstract:
 Leishmaniasis is a global illness that is endemic in many countries, including Iraq. The infection is caused by the injection of the parasite Leishmania through a female fly bite’s belonging to the genus Phlebotomus when feed on the mammal host. The hallmark of cutaneous Leishmania is skin ulcers that are likely to be effectively enhanced by the immune system to control the growth and the development of the parasite, while other species of Leishmania are more severe and the parasite infect the visceral organs of the host rather than local skin infection According to statistics and available database of Iraqi Center of Disease Control, the number of recorded cases of cutaneous leishmaniasis (CL) in Iraq were 16134 cases in 2020, while for visceral leishmaniasis (VL), it was 95 cases. The current study was conducted on 88 individaul of both sexes, they were from Diyala province and the capital Baghdad, during the period from October 2020 to February 2021. All suspected cutaneous or visceral patients involved in this study were prediagnosed in the laboratory before processing Adenosine Deaminase Enzyme (ADA) by ELISA colorimetric detection. 
 Total number of confirmed leishmaniasis patients were (n=57) cutaneous patients and(n=16) visceral patients, collected from different hospitals in Diyala province and Baghdad. Positive CL or VL samples were confirmed by microscopic Giemsa staining, rapid immune chromatographic strip assay and indirect fluorescent antibody test (IFAT), in addition to the clinical signs and symptoms, which were evaluated by a consultant physician.
 the ADA enzyme level was also increased in the studied groups where significant difference was recorded in the 2nd trail Pentostam treatment, which was 4.275 nanomol/minute/µg in comparison to control subjects, which was 3.138 nanomol/minute/µg. Although no significant correlation was seen in the ADA enzyme concentration in the newly infected and 3rd trial treatment groups, which were 3.899 nanomol/minute/µg and 3.474 nanomol/minute/µg, respectively. 
 Furthermore, the highest serum ADA enzyme concentration was observed in the newly visceral leishmaniasis groups, which was 5.238 nanomol/minute/µg. However, there was difference seen among the test groups for both studied parameters. 
 The results of this study highlighted a new concept of investigating immunological molecules, such as ADA enzyme, as possible biomarkers for cutaneous or visceral leishmaniasis prognosis and development.

Comparative study of analgesic effects of ropivacaine and dexmedetomidine with that of ropivacaine and fentanyl for lower abdominal and lower limb orthopaedic surgeries

Introduction: The anesthetic choices for lengthy lower limbs orthopedic procedures may comprise general anesthesia and limited types of regional techniques such as epidural, continuous spinal, or combined nerve blocks. Ropivacaine is a long-acting amide local anesthetic with a potentially improved safety profile when compared to bupivacaine. Dexmedetomidine and fentanyl are two such adjuvant drugs that have been used in combination with bupivacaine or ropivacaine to enhance the analgesic efficacy of the drugs and that facilitate early achievement and prolongation of block. Material and Methods: This is a Comparative, prospective and single study of postoperative epidural analgesia was done in 140 patients, posted for elective surgeries selected randomly, after approval from Ethical committee, conducted over a period of 6 months. Patients of either sex with age between 18 to 60 years. ASA grades I and II. Elective lower limb Orthopaedic and lower Abdominal surgery were included. Patients` refusal, Spinal deformities. Bleeding disorders, Neurological deficit. Local skin infection around the site of needle insertion and Allergic to local anaesthetic drugs were excluded. Results: A total of 140 patients of either sex selected in this study.

Novel Topical Drug Delivery System: Microemulgel - A Review

Topical delivery systems for drugs allow for localised drug administration through ophthalmic, vaginal, skin, and rectal routes. Topical formulations have a wide range of products designed for cosmetic or dermatological use on both healthy and diseased skin. Topical drug delivery system is generally used in where other systems of drug administration fail or it is mainly used in local skin infection like fungal infection. Topical drug delivery can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorder. A unique feature of topical drug delivery is the direct accessibility of the skin as a target organ on human body for diagnosis and treatment. Microemulsions generally contain both a surfactant and co-surfactant that induce spontaneous formation of the system. Emulgel is a combination of emulsion and gel. Emulgel is the one of the recent technologies in NDDS used for Dual action of emulsion and gel for topical drug delivery system. Emulgel is emulsions, either of the oil-in-water or water-in-oil type, which are gelled by mixing with a gelling agent. The main objective behind emulgel is delivery of hydro phobic drug via skin so that hydrophobic moiety can enjoy the unique properties of gels. Micro-emulsions are micronized, and thermodynamically stable structures with low interfacial tension prepared by adding a co-surfactant have many advantages, including increased permeability, better thermodynamic stability, and longer release times. Emulgel improves patient compliance and emulsion stability by prolonging drug release. The formulated emulgel is assessed for parameters such as pH, viscosity, globule size, Spreadability, and so on, while the micro-emulsion is assessed for parameters such as viscosity, pH, zeta-potential, and so on.

Pneumonia with empyema: rare complication after sea urchin injury

Staphylococcal pneumonias are rare, especially in immunocompetent children. They can represent a complication of tissue infection with hematogeneous dissemination. Sea urchin injuries can result in local reactions, granulomas and, unfrequently, systemic disease. We describe the case of a 16-year-old boy with a four-day fever and left-sided chest pain, with referral to a sea urchin injury five days before admission. Physical examination revealed diminished pulmonary sounds and crackles in the left lower hemithorax. The chest radiograph showed a pleural effusion. Blood tests showed leukocytosis, neutrophilia, and an elevated C-reactive protein. Empyema was diagnosed after performing a thoracentesis. Subsequently he initiated inflammatory signs with fluctuation on his right heel, with purulent drainage. Suspecting on a staphylococcal etiology, he was treated with flucloxacillin, a suspicion that was confirmed by the isolation of Staphylococcus aureus in pleural liquid and abscess material. After antibiotic treatment was established, there was a favorable clinical and radiological evolution. With this case report, we would like to draw attention to the possibility of hematogenous dissemination of a microorganism after local skin infection, even in immunocompetent individuals.

Zašto topikalni kortikosteroid plus antibiotik?

Numerous dermatoses can be treated (at least in certain phases of the disease) exclusively with local therapy. Although there is a large number of dermatological diseases, therapeutic options for local therapy are not numerous. However, adequate and timely application of available topical preparations and their combination, enables a large number of different dermatoses to be treated with a relatively small number of topical preparations. The framework of local dermatological therapy and the most commonly prescribed preparations are corticosteroids. Topical corticosteroids are used to treat inflammatory dermatoses, while they are not recommended for use in acne vulgaris, fungal and bacterial skin infections. Designing preparations that contain a topical corticosteroid and antimycotic, corticosteroid and antibiotic, and sometimes all three substances, enables the use of corticosteroids in the above-mentioned infectious skin diseases. Topically applied antibiotics play a significant role in the treatment of mild forms of acne vulgares, while in localized bacterial skin infections, their importance is such that they often make general antibiotic therapy-unnecessary. Topical corticosteroids are most often combined with oxytetracycline, bacitracin and aminoglycosides - gentamicin and neomycin. The combination of betamethasone and gentamicin in a topical preparation is often used in everyday medical practice. It is recommended for many skin diseases in which betamethasone acts anti-inflammatory, immunosuppressive, vasoconstrictive, reducing erythema, edema and skin inflammation, while gentamicin acts on gram-positive and negative bacteria that are sensitive to it and are present on the surface of affected lesions due to superinfection. Since betamethasone is a potent corticosteroid with a good effect on a large number of dermatoses and gentamicin has antibiotic and anti-inflammatory properties and effect, the combined preparation of betamethasone - gentamicin is an excellent and rational solution in local therapy of many dermatoses.

Repeated Sand Fly Bites of Infected BALB/c Mice Enhance the Development of Leishmania Lesions

Sand fly saliva has considerable immunomodulatory effects onLeishmaniainfections in mammalian hosts. Studies on severalLeishmania– sand fly - host combinations have demonstrated that co-inoculation withLeishmaniaparasites enhances pathogenicity, while pre-exposure of hosts to sand fly bites provides significant protection against infection. However, the third scenario, the effect of sand fly saliva on parasite development in hosts infected before exposure to sand flies, remains an understudied aspect ofLeishmania–host–vector interaction. Here we studied the effect of exposure ofL. major-infected BALB/c mice to repeated sand fly bites. Mice infected intradermally with sand fly-derivedLeishmaniawere repeatedly bitten byPhlebotomus duboscqifemales every two weeks. The lesion development was recorded weekly for ten weeks post-infection and parasite load and distribution in various organs were testedpost mortemusing qPCR. Repeated sand fly bites significantly enhanced the development of cutaneous lesions; they developed faster and reached larger size than in unexposed mice. Multiple sand fly bites also increased parasites load in inoculated ears. On the other hand, the distribution of parasites in mice body and their infectiousness to vectors did not differ significantly between groups. Our study provides the first evidence that multiple and repeated exposures of infected BALB/c mice to sand fly bites significantly enhance the progress of local skin infection caused byLeishmania majorand increase tissue parasite load, but do not affect the visceralization of parasites. This finding appeals to adequate protection of infected humans from sand fly bites, not only to prevent transmission but also to prevent enlarged lesions.

Nonbite Transmission of Pasteurella Causing Epiglottitis in an Immunocompetent Patient

Abstract Pasteurella infections commonly manifest as localized skin infections; however, more invasive infections can also occur. Pasteurella epiglottitis is a rare infection associated with nonbite transmission, including food and beverages contaminated with animal saliva. Fewer than 20 cases of Pasteurella epiglottitis have been reported in the literature.

New Salvage Vincristine, BCNU, Cyclophosphamide, Prednisone (VBCP) Chemotherapy for Relapsed/Refractory Multiple Myeloma in the Modern Era: A Case Series

A number of salvage high-intensity chemotherapy options have been designed to rapidly control progressive multiple myeloma (MM). We report our experience with vincristine, BNCU [carmustine], cyclophosphamide, and prednisone (VBCP), a regimen given in the outpatient setting to patients with relapsed/refractory MM (RRMM) resistant to almost all the available novel and targeted therapies. The VBCP regimen includes V 1.2 mg/m2 (max 2.0 mg) IV d1, B 20 mg/m2 IV d1, C 400 mg/m2 IV d1-4, and P 40 mg/m2 d1-7, given every 28-35 days with growth factor support. Ten patients were identified who were treated with VBCP from January 2013 to August 2016 at the University of Florida. The median age at diagnosis of MM was 63 (range, 51-73). Seventy percent had IgG kappa, 10% had IgA kappa, and 20% had kappa-only disease. These patients were heavily pretreated with a median of 5.5 prior treatment regimens (range, 4-11) including lenalidomide, pomalidomide, bortezomib, carfilzomib, cyclophosphamide, and autologous stem cell transplantation (Table 1). The objective response rate (≥ partial response) was 60% with an additional 30% achieving minimal response or stable disease. The median time to progression for patients with stable disease or better was 5.2 months. The median progression free survival was 4.4 months while the median overall survival was 12.8 months. Treatment related toxicities were mainly grade ≥ 3 anemia, thrombocytopenia, and neutropenia observed in 50%, 60%, and 60% of patients, respectively. Neutropenic fever was observed in 20% of patients. Other non-hematologic complications included tumor lysis, neuropathy, GI symptoms, localized skin and lung infections, and atrial fibrillation. Despite the above toxicities, 61% of the subsequent cycles were given on time within 28-35 days. No treatment-related mortality was observed. Our results suggest VBCP may be a highly active and tolerable salvage regimen with impressive response rate among heavily pre-treated patients with RRMM who already failed many of the novel agents. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effect analysis of sequential laser application in treating the hypertrophic scars of burn children at early stage

Objective: To explore the effects of sequential application of intensive pulsed light and carbon dioxide laser in treating the hypertrophic scars of burn children at early stage. Methods: A retrospective cohort before-after control study in the same patients was conducted. From January 2016 to December 2018, 145 burn children with hypertrophic scar at the early stage who met the inclusion criteria were admitted to the First Hospital of Jilin University, including 82 males and 63 females, aged 1 to 12 (3 (2, 6)) years. All the children were firstly treated with intense pulsed light therapy (no anesthesia or intravenous-inhalation combined anesthesia) at an interval of once per month, and then changed to carbon dioxide laser therapy (topical anesthesia or intravenous-inhalation combined anesthesia) when the degree of scar hyperemia was reduced, at an interval of once every 3 months, for a total of 3 times. Before the first intense pulsed light treatment (hereinafter referred to as before the first treatment) and 3 months after the last carbon dioxide laser treatment (hereinafter referred to as after the last treatment), scar scoring was evaluated by Vancouver Scar Scale (VSS), and scar hyperemia (denoted as hemoglobin level) was measured with Antera 3D® camera. The times of intense pulsed light, the time of single treatment, the anesthesia method, and the time of intravenous-inhalation combined anesthesia of intense pulsed light and carbon dioxide laser treatment were analyzed. After the last treatment, Likert Scale was used to evaluate the efficacy satisfaction of both doctors and patients. Adverse reactions were recorded during the treatment. Data were statistically analyzed with Wilcoxon signed rank sum test, and paired sample t test. Results: The color, vascular distribution, thickness, and softness scores, and total score in VSS scoring of scars of children after the last treatment were significantly lower than those before the first treatment (Z=-6.05, -10.34, -9.84, -9.28, -10.43, P<0.01). The hemoglobin level of scar of children after the last treatment was 1.86±0.24, significantly lower than 2.27±0.32 before the first treatment (t=17.65, P<0.01). A total of 411 times of intense pulsed light therapy were performed, (2.8±0.6) times per person, and the single treatment time was 35 (20, 45) s. There were 392 times (95.38%) without anesthesia, and 19 times (4.62%) with intravenous-inhalation combined anesthesia with time of 6 (5, 8) min. The single treatment time of carbon dioxide laser therapy was 5 (3, 10) min. There were 364 times (83.68%) of topical anesthesia and 71 times (16.32%) of intravenous-inhalation combined anesthesia with time of 10 (8, 15) min. After the last treatment, the efficacy satisfaction scores of doctors and patients were (4.3±0.7) and (3.8±1.0) points, respectively. Blisters occurred in 5 cases after intense pulsed light treatment, which were healed naturally after drainage. One child developed local skin infection, skin redness and swelling accompanied by purulent exudate after carbon dioxide laser treatment, which was improved after skin disinfection and external use of mupirocin ointment. No inflammatory pigmentation, worsening of hyperplasia of scar, erythema, or other skin adverse reactions or anesthetics-related adverse reactions occurred in any child. Conclusions: Sequential application of intense pulsed light and carbon dioxide laser to treat the hypertrophic scars of burn children at early stage can obviously improve the appearance and texture of scar, with higher satisfaction of doctors and patients and fewer adverse reactions.

A porcine model of subcutaneous Staphylococcus aureus infection: a pilot study

In this descriptive pilot study, we aim to establish a porcine Staphylococcus aureus skin infection model by subcutaneous injection (s.c.) of the porcine S54F9 S. aureus strain in the groin area. Six pigs were used in the study: Five pigs were injected with S. aureus, inocula ranging from 7 × 103 to 5 × 107 colony-forming units per kg bodyweight; one pig was injected with saline exclusively. Lesions were recorded up to 6 days postinoculation using clinical evaluation, ultrasound evaluation, microbiology, flow cytometry, and pathology. Inoculation gave rise to lesions ranging from localized skin infection, that is, minute histological changes, intracellular infection, and macroscopic abscess formation with sequestration of soft tissue, to generalized infection and development of disseminated intravascular coagulation necessitating euthanasia only 10 h after inoculation. Ultrasound assessment of maximum width and characteristics was not able to disclose the progress of the local infection. Flow cytometry and immunohistochemistry revealed the participation of γδT cells in the immune response. In conclusion, we did see a graded inflammatory response associated with the dose of s.c. inoculated bacteria, which may be useful for studying, in particular, the interaction of bacteria and inflammatory mononuclear cell populations. It needs to be investigated if the model is discriminatory and robust.

Skincare interventions in infants for preventing eczema and food allergy: A cochrane systematic review and individual participant data meta-analysis.

Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. A prospectively planned individual participant data meta-analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy. Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020. Included studies were randomized controlled trials of infants <1year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3years. Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta-analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3-12months. Skincare interventions probably do not change risk of eczema by age 1-3years (RR 1.03, 95% CI 0.81, 1.31; I2 =41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1-3years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I2 =0%; moderate certainty; 2728 participants, 6 trials). Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections.

A Murine Skin Infection Model Capable of Differentiating the Dermatopathology of Community-Associated MRSA Strain USA300 from Other MRSA Strains.

USA300 is a predominant and highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain that is a leading cause of skin and soft tissue infections. We established a murine intradermal infection model capable of demonstrating dermatopathological differences between USA300 and other MRSA strains. In this model, USA300 induced dermonecrosis, uniformly presenting as extensive open lesions with a histologically documented profound inflammatory cell infiltrate extending below the subcutis. In contrast, USA400 and a colonizing control strain M92 caused only localized non-ulcerated skin infections associated with a mild focal inflammatory infiltrate. It was also determined that the dermonecrosis induced by USA300 was associated with significantly increased neutrophil recruitment, inhibition of an antibacterial response, and increased production of cytokines/chemokines associated with disease severity. These results suggest that induction of severe skin lesions by USA300 is related to over-activation of neutrophils, inhibition of host antibacterial responses, and selective alteration of host cytokine/chemokine profiles.

Site-Specific Conjugation of Cell Wall Polyrhamnose to Protein SpyAD Envisioning a Safe Universal Group A Streptococcal Vaccine.

Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus (GAS) is a public health priority. The species defining group A cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant N-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity in rheumatic heart disease, leaving its polyrhamnose core (GACPR). Here we generate a novel protein conjugate of the GACPR and test the utility of this conjugate antigen in active immunization. Instead of conjugation to a standard carrier protein, we selected SpyAD, a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen. SpyAD was synthesized using the XpressTM cell-free protein expression system, incorporating a non-natural amino acid to which GACPR was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GACPR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes. The conjugated SpyAD-GACPR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils. Active immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR, together with candidate vaccine antigens streptolysin O and C5a peptidase, protected against GAS challenge in a systemic infection model and localized skin infection model, without evidence of cross reactivity to human heart or brain tissue epitopes. This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.

Melioidosis: A Fulminant Infection in a Patient with Uncontrolled Diabetes

AbstractMelioidosis is an endemic infection in Southeast Asia and Northern Australia commonly manifesting with pneumonia and localized skin infection. Though most exposures do not lead to severe illness, a fulminant infection can occur among patients with risk factors. A 59-year-old male presented with cough with expectoration and fever for 1 week. He had diabetes for 10 years with poorly controlled blood sugars. Contrast-enhanced computerized tomography (CECT) of thorax showed right upper lobe consolidation with diffuse ground-glass opacities in right upper lobe along with microabscesses in liver and spleen. Sputum culture and Xpert mycobacterium tuberculosis complex and resistance to rifampin (MTB/RIF) for tuberculosis were negative. Bronchoalveolar lavage culture grew Burkholderia pseudomallei. He was treated with initial intensive therapy with injection amoxicillin-clavulanic acid for 2 weeks and subsequently started on eradication therapy with tablet trimethoprim-sulfamethoxazole. Diagnosis of melioidosis should be considered in a patient of pneumonia with multiorgan involvement in an endemic area, especially with underlying risk factors.