Chitosomes-In-Chitosan Hydrogel for Acute Skin Injuries: Prevention and Infection Control.

Burns and other skin injuries are growing concerns as well as challenges in an era of antimicrobial resistance. Novel treatment options to improve the prevention and eradication of infectious skin biofilm-producing pathogens, while enhancing wound healing, are urgently needed for the timely treatment of infection-prone injuries. Treatment of acute skin injuries requires tailoring of formulation to assure both proper skin retention and the appropriate release of incorporated antimicrobials. The challenge remains to formulate antimicrobials with low water solubility, which often requires carriers as the primary vehicle, followed by a secondary skin-friendly vehicle. We focused on widely used chlorhexidine formulated in the chitosan-infused nanocarriers, chitosomes, incorporated into chitosan hydrogel for improved treatment of skin injuries. To prove our hypothesis, lipid nanocarriers and chitosan-comprising nanocarriers (≈250 nm) with membrane-active antimicrobial chlorhexidine were optimized and incorporated into chitosan hydrogel. The biological and antibacterial effects of both vesicles and a vesicles-in-hydrogel system were evaluated. The chitosomes-in-chitosan hydrogel formulation demonstrated promising physical properties and were proven safe. Additionally, the chitosan-based systems, both chitosomes and chitosan hydrogel, showed an improved antimicrobial effect against S. aureus and S. epidermidis compared to the formulations without chitosan. The novel formulation could serve as a foundation for infection prevention and bacterial eradication in acute wounds.

A randomized controlled trial of a brief behavioral intervention to reduce skin and soft tissue infections among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) are at high risk for skin and soft tissue infections (SSTIs), but few interventions have targeted their reduction. The goal of the current study was to test the effects of a brief skin and needle hygiene behavioral intervention (SKIN) in a two-group randomized controlled trial with 12-month follow-up. METHOD: PWID (N = 252) were recruited from inpatient hospital units at a single urban medical center site and randomly assigned to an assessment-only (AO) condition or SKIN, which was a two-session intervention that included psychoeducation, behavioral skills demonstrations, and motivational interviewing. Mixed effects generalized linear models assessed the impact of the intervention on frequency of: 1) self-reported SSTIs, 2) uncleaned skin injections, and 3) injection. RESULTS: Participants were 58.3 % male, 59.5 % White, and averaged 38 years of age. SKIN participants had 35 % fewer SSTIs compared to AO (p = .179), a difference of nearly one infection per year. The mean rate of uncleaned skin injections was about 66 % lower (IRR = 0.34, 95 % CI 0.20; 0.59, p < .001) among SKIN participants compared to AO. Almost one-third of participants reported no injection over follow-up and the mean rate of injection during follow-up was about 39 % lower (IRR = 0.61; 95 % CI 0.36; 1.02, p = .058) among persons randomized to SKIN than AO. CONCLUSIONS: The SKIN intervention reduced uncleaned skin injections but did not reduce SSTIs significantly more than a control condition. Brief interventions can improve high-risk practices among PWID and lead to clinically meaningful outcomes.

Immunization with nontreponemal antigen alters the course of experimental syphilis in the rabbit model.

The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 106T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera.

Infection prevention and control challenges in Flemish homecare nursing: a pilot study.

Home nursing is evolving towards more invasive care. Nevertheless, no national data are available on the prevalence of HAI in this setting. The aim of this pilot study is to explore the Flemish home care setting as a first step toward a national surveillance program. A survey, focused on patient characteristics and HAI, was conducted between 7 May and 20 July 2018 on 711 Flemish patients. Most of the patients (74%) are 65 years or older and half of them had a form of comorbidity. Assisting with personal hygiene and wound care were the most frequent services delivered by home care nurses. A comparison of the prevalence of infections diagnosed by a physician or applying uniform criteria (ECDC), revealed a similar prevalence of skin and soft tissue infections (9% vs. 8.5%) and urinary tract infections (4% vs. 4.5%). A positive MDRO-screening was found in 6% of the patients. This pilot study is a first step towards a standardized national surveillance in home care to collect information on the prevalence of HAI and it reveals several interesting facts and study pitfalls for this setting.

Moisture-associated skin damage: an overview of its diagnosis and management.

This educational article introduces an explores moisture-associated skin damage (MASD) and the four forms it manifests as, namely, incontinence-associated dermatitis; intertriginous dermatitis; peristomal moisture-associated dermatitis; and peri-wound moisture-associated dermatitis. The aetiology and predisposing factors of each form are critically discussed, in addition to the treatments and interventions that can be used by nurses to support patient recovery. Nurses and other health professionals working with patients who are at risk of skin damage or who already require wound care, must be knowledgeable about all aspects of MASD. Fortunately, a plethora of evidence-based literature exists to support health professionals in their practice, although validated assessment and recording tools for incontinence-associated dermatitis are limited.

Perceived Behavioral Control and Barriers to Cleaning Skin Before Injecting Drugs.

OBJECTIVES: Skin and soft-tissue infections (SSTI) among people who inject drugs (PWID) are common and represent a significant public health burden. In the current study, we examined the relationship between perceived behavioral control and perceived barriers to cleaning skin before injecting drugs. METHODS: Participants (n = 248; 37.9 [±10.7] years of age, 58.5% male, 59.3% white, 16.1% Hispanic) were patients seeking medical care at a large urban hospital in the northeastern United States. We used ordinary least squares regression to estimate the associations between perceived barriers to skin cleaning with background characteristics and perceived behavioral control. RESULTS: Controlling for background and other study variables, greater number of past-year skin abscesses was associated with greater level of perceived barriers to skin cleaning (P < 0.001), whereas higher level of education and higher perceived behavioral control were associated with lower levels of perceived barriers to skin cleaning (P < 0.001). CONCLUSIONS: Interventions aiming to reduce the likelihood for SSTI among people who inject drugs may benefit from strengthening individual's behavioral control and providing skin cleaning skills training.

Outpatient dermatology consultations for oncology patients with acute dermatologic adverse events impact anticancer therapy interruption: a retrospective study.

BACKGROUND: Dermatologic adverse events (dAEs) of anticancer therapies may negatively impact dosing and quality of life. While therapy interruption patterns due to dAEs have been studied in hospitalized cancer patients, similar outcomes in outpatient oncodermatology are lacking. OBJECTIVES: To analyse the therapy interruption patterns, clinico-histopathologic characteristics and management outcomes of outpatient dermatology consultations for acute dAEs attributed to the most frequently interrupted class of oncologic agents. METHODS: We performed a retrospective cohort study of all cancer patients who received a same-day outpatient dermatology consultation for acute dAEs at our institution from 1 January to 30 June 2015. Relevant data were abstracted from electronic medical records, including demographics, oncologic history and explicit recommendations by both the referring clinician and consulting dermatologist on anticancer therapy interruption. Consultations with the most frequently interrupted class of oncologic treatment were characterized according to clinico-histopathologic features, dermatologic management and clinical outcomes. RESULTS: There were 426 same-day outpatient dermatology consultations (median age 59, 60% female, 30% breast cancer), of which 295 (69%) had systemic anticancer therapy administered within 30 days prior. There was weak inter-rater agreement between referring clinicians and consulting dermatologists on interruption of anticancer treatment (n = 150, κ = 0.096; 95% CI -0.02 to 0.21). Seventy-three (25%) consultations involved interruption by the referring clinician, most commonly targeted therapy (24, 33%). Maculopapular rash was commonly observed in 23 consultations with 25 dAEs attributed to targeted agents (48%), and topical corticosteroids were most frequently utilized for management (22, 38%). The majority (83%) of consultations with targeted therapy-induced dAEs responded to dermatologic treatment and 84% resumed oncologic therapy, although three (19%) at a reduced dose. Rash recurred only in two instances (13%). CONCLUSIONS: A high frequency of positive outcomes in the management of targeted therapy-induced dAEs by outpatient consulting dermatologists and low recurrence of skin toxicity suggests impactful reductions in interruption of anticancer therapy.

Halogenated boroxine dipotassium trioxohydroxytetrafluorotriborate K2[B3O3F4OH] inhibits emerging multidrug-resistant and ß-lactamase-producing opportunistic pathogens.

Halogenated boroxine dipotassium trioxohydroxytetrafluorotriborate, K2[B3O3F4OH] (boroxine) was previously shown to be very effective in inhibition of several carcinoma cell lines, including the skin cancer. Here, we investigated its antimicrobial potential by targeting the multidrug-resistant opportunistic pathogens associated with skin and wound infections. The antimicrobial testing against eleven bacterial and four fungal species revealed good activity of boroxine against pathogenic filamentous fungi Penicillium funiculosum and Aspergillus niger (MIC50 64 and 128 µg/ml), and a moderate bioactivity against the yeast Candida albicans (MIC50 512 µg/ml). Among the tested multidrug-resistant bacteria, the best antibacterial effect, stable over a 24-h period, was observed against the methicillin-resistant Staphylococcus aureus strain (MRSA) at MIC of 1024 µg/ml. The atomic force microscopy (AFM) used to investigate the morphology of S. aureus cells revealed indentations on its cell envelope after the boroxine exposure. These results show that in addition to the antitumor effect, boroxine exerts wide spectrum antimicrobial activity, thus may help preventing the development of skin and wound-related opportunistic infections.

Connecting the Dots: From Skin Barrier Dysfunction to Allergic Sensitization, and the Role of Moisturizers in Repairing the Skin Barrier

The skin is one of the largest immunologic organs in the body and a continuous target for allergic and immunologic responses. Impairment of the skin barrier increases the likelihood of external antigens and pathogens entering and creating inflammation, which can potentially lead to skin infections, allergies, and chronic inflammatory diseases such as atopic and contact dermatitis. Functionally, the skin barrier can be divided into four different levels. From outermost to innermost, these highly interdependent levels are the microbiome, chemical, physical, and immune levels. The objective of this review is to provide an update on current knowledge about the relationship between skin barrier function and how dysfunction at each level of the skin barrier can lead to allergic sensitization, contact dermatitis, and the atopic march, and examine how to best repair and maintain this barrier through the use of moisturizers. J Drugs Dermatol. 2019;18(6):581-586.

Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis.

BACKGROUND: Patients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. OBJECTIVE: The aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD. METHODS: This analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates. RESULTS: Of 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p < 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44; p < 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31; p < 0.01). Systemic anti-infective medication use was lower with dupilumab. CONCLUSIONS: Dupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD. CLINICALTRIALS. GOV IDENTIFIERS: NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

Synthetic Turf: History, Design, Maintenance, and Athlete Safety.

CONTEXT:: Synthetic turf has become an increasingly common playing surface for athletics and has changed dramatically since its introduction more than 50 years ago. Along with changes to surface design, maintenance needs and recommendations have become more standardized and attentive both to upkeep and player-level factors. In particular, synthetic turf maintenance as it relates to athlete health and safety is an important consideration at all levels of play. EVIDENCE ACQUISITION:: A literature search of MEDLINE and PubMed for publications between the years 1990 and 2018 was conducted. Keywords included s ynthetic turf, artificial turf, field turf, and playing surface. Additionally, expert opinion through systematic interviews and practical implementation were obtained on synthetic turf design and maintenance practices in the National Football League. STUDY DESIGN:: Clinical review. LEVEL OF EVIDENCE:: Level 5. RESULTS:: Synthetic turf has changed considerably since its inception. Playing surface is a critical component of the athletic environment, playing a role both in performance and in athlete safety. There are several important structural considerations of third-generation synthetic turf systems currently used in the United States that rely heavily on strong and consistent maintenance. A common misconception is that synthetic turf is maintenance free; in fact, however, these surfaces require routine maintenance. Whether athletes experience more injuries on synthetic over natural surfaces is also of interest among various levels and types of sport. CONCLUSION:: Modern synthetic turf is far different than when originally introduced. It requires routine maintenance, even at the level of local athletics. It is important for sports medicine personnel to be familiar with playing surface issues as they are often treating athletes at the time of injury and should maintain a level of awareness of contemporary research and practices regarding the relationships between synthetic turf and injury.

Prevalence and risk factors for injection site skin infections among people who inject drugs (PWID) in Tehran.

BACKGROUND/OBJECTIVES: Injection drug use is one of the major public health problems in Iran. Injection drug use is associated with numerous negative health outcomes, such as blood-borne infections (HIV, HCV) and injection site skin infections (abscesses, cellulitis). The aim of this study was to determine prevalence of injection site skin infections and its associated risk factors among people who inject drugs (PWID) in Tehran, Iran. METHODS: The cross-sectional study was conducted from March to August 2016 in Tehran province. A total of 500 PWID were recruited by convenience and snowball sampling from Drop-in Centers (DIC) in the South of Tehran. Our primary outcomes were self-report of ever having injection sites skin infections and receiving treatment for them. We first examined associations between individual variables and lifetime history of having injection site infections in bivariate analysis using the chi-square or Fisher's exact tests, as appropriate. Variables with P-value <.2 were included in a multiple logistic regression model. RESULTS: Overall, 40% (CI95%: 30.3%, 52.2%) of participants reported ever having an injection site infection. In the multivariable model, those with low socioeconomic status (AOR = 2.4, P = .03), self-reported as HIV positive (AOR =1.6, P = .01), reporting more than 3 injections per day (AOR = 4.1, P = .03) and reuse of their own syringes (AOR = 8.5, P = .03) were more likely to have injection sites skin infections. PWID who used needle and syringe program (NSP) services were less likely to report injection site infections (AOR = 0.5, P = .04). CONCLUSION: We have identified several risk factors for injection sites infections among PWID, including frequency of injection per day, reuse of their own syringes, not using NSP services, HIV status, socioeconomic status with skin infections in PWID. Prevention strategies to reduce skin infections should focus on high-risk injection behaviors and improving access to NSP services.

Thermal stability of mafenide and amphotericin B topical solution.

OBJECTIVE: Fungal infections remain a major cause of mortality in the burned population. Mafenide acetate/amphotericin B solution (SMAT) has been used topically for prophylaxis and treatment of these infections. Current manufacturer guidelines only guarantee the stability of mafenide solution and amphotericin B at room temperature. Additionally, the recommended maximum storage time for mafenide solution is 48h, leading to significant financial and material loss when unused solutions are discarded. The purpose of this study was to characterize the chemical stability, structure and bioactivity of SMAT stored at 2°C, 25°C, and 40°C for up to 90 days. METHODS: Stability analyses of SMAT solutions containing 2.5% or 5% mafenide plus 2µg/mL amphotericin B were performed using high performance liquid chromatography. Chemical structure was assessed using Fourier-transform infrared spectroscopy. Bioactivity against clinically relevant species was examined. RESULTS: The chemical structure and stability of mafenide did not change over 90days at all temperatures. Amphotericin B was undetectable in SMAT solutions after two days at high temperatures, which was slowed by refrigerated storage. Against Staphylococcus aureus, SMAT activity began to decrease generally between two and seven days. Against Pseudomonas aeruginosa, activity slowly tapered and was gone by day 90. SMAT retained high bioactivity against Candida albicans for over 40days and was not affected by temperature. CONCLUSIONS: The amphotericin B component of SMAT is degraded within 2days under warm storage. While mafenide was stable over 90 days, the bioactivity of SMAT solution may be lost within 2days as well.

Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials.

BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier defects, T helper type 2 cell activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. OBJECTIVE: We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RRs) and 95% confidence intervals (CIs) for skin infections, herpesvirus infections, and overall infections and infestations were calculated for dupilumab compared with for placebo by using binary random effects meta-analysis. For the analysis of eczema herpeticum, Peto odds ratios were calculated. RESULTS: Eight randomized controlled trials in 4 publications with 2706 participants were included, with follow-up time ranging from 4 to 52 weeks. Meta-analysis including all dosing schedules and follow-up times showed a RR of skin infection of 0.54 (95% CI, 0.42-0.70) and an odds ratio of eczema herpeticum of 0.34 (95% CI, 0.14-0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR, 1.16; 95% CI, 0.78-1.74) and overall infections (RR, 0.98; 95% CI, 0.83-1.16). LIMITATIONS: Our analysis is limited by the short follow-up time in most trials and the relatively low number of patients treated with dupilumab to date. CONCLUSIONS: Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD. The mechanism underlying this association is uncertain but is likely related to improvement in AD severity. Dupilumab, a monoclonal antibody targeting interleukin 4 and interleukin 13, appears to significantly decrease the risk for skin infections and eczema herpeticum in adults with moderate-to-severe AD.

Skin Infections: Which Student-Athletes Are at Greatest Risk?

Skin infections are a common ailment that affect all students, with increased risk to those students participating in sport and specifically contact sports. The types of skin infections that students are likely to encounter are categorized into three types: (a) bacterial, (b) viral, and (c) fungal. All three types of infection can appear benign at onset but can grow into serious disease and illness if not correctly identified and treated in a timely manner. A strong prevention program should be in place at all schools with appropriate resources in place (human and financial) to carry out proper cleaning of facilities, on-site examination by the school nurse or athletic trainer, and sufficient education of coaches, athletes, parents and administrators.

Early infectious outcomes after addition of fluoroquinolone or aminoglycoside to posttrauma antibiotic prophylaxis in combat-related open fracture injuries.

BACKGROUND: We examined combat-related open extremity fracture infections as a function of whether posttrauma antimicrobial prophylaxis included expanded Gram-negative (EGN) coverage. METHODS: Military personnel with open extremity fractures sustained in Iraq and Afghanistan (2009-2014) who transferred to participating hospitals in the United States were assessed. The analysis was restricted to patients with a U.S. hospitalization period of ≥7 days. Prophylaxis was classified as narrow (e.g., IV cefazolin, clindamycin, and/or amoxicillin-clavulanate) or EGN, if the prophylactic regimen included fluoroquinolones and/or aminoglycosides. RESULTS: The study population included 1,044 patients, of which 585 (56%) and 459 (44%) received narrow and EGN coverage, respectively (p < 0.001). Skin and soft-tissue infections (SSTIs) were more common among patients who received narrow prophylaxis compared to EGN coverage (28% vs. 22%; p = 0.029), whereas osteomyelitis rates were comparable between regimens (8%). Similar findings were noted when endpoints were measured at 2 and 4 weeks postinjury. There was no significant difference related to length of hospitalization between narrow and EGN regimens (median: 34 and 32 days, respectively) or operating room visits (median: 5 and 4). A higher proportion of EGN coverage patients had Gram-negative organisms isolated that were not susceptible to fluoroquinolones and/or aminoglycosides (49% vs. 40%; p < 0.001). In a Cox proportional model, narrow prophylaxis was independently associated with an increased risk of extremity SSTIs (hazard ratio: 1.41; 95% confidence interval: 1.09-1.83). DISCUSSION: Despite seeing a small benefit with EGN coverage related to a reduction of SSTIs, it does not decrease the risk of osteomyelitis, and there seems to be a cost of increased antibiotic resistance associated with use. Overall, our findings support the current post-combat trauma antibiotic prophylaxis guidelines, which recommend the use of cefazolin or clindamycin with open fractures. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level II; Therapy, level IV.

Novedades en patología infecciosa para un pediatra de Atención Primaria / Novelties on infectious pathology for a Primary Care pediatrician

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The potential benefits of using aloe vera in stoma patient skin care.

Individuals living with an ostomy may suffer from a variety of peri-stomal skin complications related to the use of their stoma appliance or accessories. These conditions can be serious enough to significantly impact on a patient's quality of life and may result in severe clinical complications (such as infection). This article is a review of the literature with the objective of investigating and presenting evidence for the well-documented use of aloe vera in the prevention of skin conditions similar to those seen in peri-stomal skin complications. An exploration for the potential use of aloe vera directly or indirectly (as an adjunct to medical devices such as wafers) in stoma patients is presented with the view that this use may be beneficial in the prevention of such peri-stomal skin complications.