Distinct T cell signatures are associated with Staphylococcus aureus skin infection in pediatric atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S. aureus responses; however, correlates of T cell immunity against S. aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S. aureus skin infection (ADS.aureus) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. ADS.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in ADS.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S. aureus in AD.

Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus.

Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was rare in blood, nose, and skin strains, suggesting a particularly important role of Lip2 for host - microbe interactions. In a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid (a human-specific AFA) in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth in otherwise inhospitable niches.

Emergence and spread of a mupirocin-resistant variant of the European epidemic fusidic acid-resistant impetigo clone of Staphylococcus aureus, Belgium, 2013 to 2023.

BackgroundAntimicrobial resistance to mupirocin and fusidic acid, which are used for treatment of skin infections caused by Staphylococcus aureus, is of concern.AimTo investigate resistance to fusidic acid and mupirocin in meticillin-susceptible S. aureus (MSSA) from community-acquired skin and soft tissue infections (SSTIs) in Belgium.MethodsWe collected 2013-2023 data on fusidic acid and mupirocin resistance in SSTI-associated MSSA from two large Belgian laboratories. Resistant MSSA isolates sent to the Belgian Staphylococci Reference Centre were spa-typed and analysed for the presence of the eta and etb virulence genes and the mupA resistance gene. In addition, we whole genome sequenced MSSA isolates collected between October 2021 and September 2023.ResultsMupirocin resistance increased between 2013 and 2023 from 0.5-1.5% to 1.7-5.6%. Between 2018 and 2023, 91.4% (64/70) of mupirocin-resistant isolates were co-resistant to fusidic acid. By September 2023, between 8.9% (15/168) and 10.1% (11/109) of children isolates from the two laboratories were co-resistant. Of the 33 sequenced isolates, 29 were sequence type 121, clonal and more distantly related to the European epidemic fusidic acid-resistant impetigo clone (EEFIC) observed in Belgium in 2020. These isolates carried the mupA and fusB genes conferring resistance to mupirocin and fusidic acid, respectively, and the eta and etb virulence genes.ConclusionWe highlight the spread of a mupirocin-resistant EEFIC in children, with a seasonal trend for the third quarter of the year. This is of concern because this variant is resistant to the two main topical antibiotics used to treat impetigo in Belgium.

Antioxidant and antibacterial hydrogel formed by protocatechualdehyde-ferric iron complex and aminopolysaccharide for infected wound healing.

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe3+) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.

Whole Genome Sequencing and Comparative Genomics of Six Staphylococcus schleiferi and Staphylococcus coagulans Isolates.

Staphylococcus schleiferi and Staphylococcus coagulans, closely related bacterial species within the Staphylococcus genus, present a challenge in classification and diagnosis due to their close genetic proximity and overlapping phenotypic features. Moreover, our understanding of the virulence mechanisms in staphylococcal species, beyond the extensively studied Staphylococcus aureus, remains limited, underscoring the importance of using comparative data to enhance our insights into virulence within these bacterial species. This study employed a comprehensive approach, utilizing comparative genomics, to identify genomic distinctions between S. schleiferi and S. coagulans, aiming to address the challenges in the accurate classification and diagnosis of these organisms and identify unique features. Whole genome sequencing was performed on six clinical isolates, and their genomes were compared to identify variations in gene content and virulence factors. De novo assembly and annotation revealed two samples as S. coagulans and four samples as S. schleiferi. Analysis of the core genomes revealed conserved regions crucial for defining species identity, while accessory genomic elements contained unique genes, possibly impacting the pathogenicity of the species.

Epidemiology and clinical features of Skin and Soft Tissue Infections Caused by PVL-Positive and PVL-Negative Methicillin-Resistant Staphylococcus aureus Isolates in inpatients in China: a single-center retrospective 7-year study.

Previous studies have mainly focused on outpatient cases of skin and soft tissue infections (SSTIs), with limited attention to inpatient occurrences. Thus, we aimed to compare the clinical parameters of inpatients with SSTIs, performed genomic characterization, and determined the subtypes of Panton-Valentine leucocidin (PVL) bacteriophages of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from these patients. We found that PVL-positive patients had shorter hospital stays (mean, 9 vs. 24 days; p < 0.001) and abscess resolution durations (mean, 8 vs. 13 days; p < 0.01). PVL-positive MRSA-induced SSTIs were more frequently associated with abscesses [36/55 (65.5%) vs. 15/124 (12.1%), p < 0.001], with 52.7% undergoing incision and drainage; over 80% of PVL-negative patients received incision, drainage, and antibiotics. In PVL-positive patients receiving empirical antibiotics, anti-staphylococcal agents such as vancomycin and linezolid were administered less frequently (32.7%, 18/55) than in PVL-negative patients (74.2%, 92/124), indicating that patients with PVL-positive SSTIs are more likely to require surgical drainage rather than antimicrobial treatment. We also found that the ST59 lineage was predominant, regardless of PVL status (41.3%, 74/179). Additionally, we investigated the linear structure of the lukSF-PV gene, revealing that major clusters were associated with specific STs, suggesting independent acquisition of PVL by different strain types and indicating that significant diversity was observed even within PVL-positive strains detected in the same facility. Overall, our study provides comprehensive insights into the clinical, genetic, and phage-related aspects of MRSA-induced SSTIs in hospitalized patients and contributes to a more profound understanding of the epidemiology and evolution of these pathogens in the Chinese population.

Assessing the Concordance of MRSA Carriage Screening With MRSA Infections.

OBJECTIVES: This study focused on children with confirmed methicillin-resistant Staphylococcus aureus (MRSA) infections to determine MRSA screening utility in guiding empirical anti-MRSA treatment of children without history of MRSA infection. We examined the concordance of screens to assess differences by infection type and used statistical analysis to determine significant contributors to concordance. METHODS: Pediatric hospital patients admitted from 2002 through 2022 were included. Subjects had MRSA infections subsequent to MRSA surveillance screens performed the preceding year. Statistical analysis identified associations between MRSA screens and infections. Number needed to treat analysis calculated the utility of rescreening. RESULTS: Among 246 subjects, 39.0% had concordant screens; 151 (61.4%) screens were obtained in the 2 weeks preceding infection. Sensitivity for bacteremia was 50.0% (n = 42), for endotracheal/respiratory 44.4% (n = 81), and 29.4% (n = 102) for skin and soft-tissue infection. For children aged younger than 6 months, sensitivity was 35.9% (n = 78). Multivariable analysis significantly associated days since screening with decreasing likelihood of concordance. Regression modeled the probability of concordance to drop below 50.0% for all infections after 4 days, after 6 days for bacteremia specifically, and 12 days for endotracheal/respiratory infections. CONCLUSIONS: The concordance of screens was far lower than negative predictive values found previously; earlier studies were possibly impacted by low prevalence and exclusion of children at high risk to inform high negative predictive values. We suggest that negative MRSA screens should not invalidate reasonable suspicion for MRSA infection in patients with high pretest probabilities.

Nanosecond pulsed electric fields increase antibiotic susceptibility in methicillin-resistant Staphylococcus aureus.

IMPORTANCE: We have found that treatment with short electric pulses potentiates the effects of multiple antibiotics against methicillin-resistant Staphylococcus aureus. By reducing the dose of antibiotic necessary to be effective, co-treatment with electric pulses could amplify the effects of standard antibiotic dosing to treat S. aureus infections such as skin and soft-tissue infections (SSTIs). SSTIs are accessible to physical intervention and are good candidates for electric pulse co-treatment, which could be adopted as a step-in wound and abscess debridement.

Human Skin T Cells Express Conserved T-Cell Receptors that Cross-React with Staphylococcal Superantigens and CD1a.

Human Langerhans cells highly express CD1a antigen-presenting molecules. To understand the functions of CD1a in human skin, we used CD1a tetramers to capture T cells and determine their effector functions and TCR patterns. Skin T cells from all donors showed CD1a tetramer staining, which in three cases exceeded 10% of skin T cells. CD1a tetramer-positive T cells produced diverse cytokines, including IL-2, IL-4, IL-5, IL-9, IL-17, IL-22, and IFN-γ. Conserved TCRs often recognize nonpolymorphic antigen-presenting molecules, but no TCR motifs are known for CD1a. We detected highly conserved TCRs that used TRAV34 and TRBV28 variable genes, which is a known motif for recognition of staphylococcal enterotoxin B, a superantigen associated with atopic dermatitis. We found that these conserved TCRs did not respond to superantigen presented by CD1a, but instead showed a cross-reactive response with two targets: CD1a and staphylococcal enterotoxin B presented by classical major histocompatibility complex II. These studies identify a conserved human TCR motif for CD1a-reactive T cells. Furthermore, the demonstrated cross-reaction of T cells with two common skin-specific stimuli suggests a candidate mechanism by which CD1a and skin flora could synergize during natural immune response and in Staphylococcus-associated skin diseases.

Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma.

Erythritol (ERT) and L-ascorbyl-2-phosphate (APS) are bacteriostatic, but their effects on staphylococcal skin infections remain unknown. We aimed to determine whether ERT combined with APS inhibits the growth of staphylococci that are commonly isolated from pyoderma skin lesions in dogs. We investigated the individual and combined effects of ERT and APS on the growth of Staphylococcus pseudintermedius, S. schleiferi, and S. aureus using turbidity assays in vitro. Skin lesions from 10 dogs with superficial pyoderma were topically treated with 5% ERT and 0.1% APS for 28 days, and swabbed skin samples were then analyzed using 16S rRNA amplicon sequencing and quantitative real-time PCR (qPCR). Results showed that ERT inhibited S. pseudintermedius growth regardless of harboring the mecA gene, and APS increased the inhibitory effects of ERT against S. pseudintermedius, S. schleiferi, and S. aureus in vitro. Moreover, combined ERT and APS decreased the prevalence of staphylococci on canine skin lesions at the genus level. The combination slightly increased the α-diversity but did not affect the ß-diversity of the microbiota. The qPCR results revealed that the combination significantly decreased S. pseudintermedius and S. schleiferi in skin lesions. Topical administration of EPS combined with APS can prevent staphylococcal colonization on the surface of mammalian skin. The results of this study may provide an alternative to systemic antibiotics for treating superficial pyoderma on mammalian skin surfaces.

Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification.

Background: People living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). The serum immune factors associated with the onset of SSTI are not well understood. Methods: We conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electro-chemiluminescence based multiplex assay platform. Results: Of 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI. Conclusion: The study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI.

Metabolic rewiring tunes dermal macrophages in staphylococcal skin infection.

The skin needs to balance tolerance of colonizing microflora with rapid detection of potential pathogens. Flexible response mechanisms would seem most suitable to accommodate the dynamic challenges of effective antimicrobial defense and restoration of tissue homeostasis. Here, we dissected macrophage-intrinsic mechanisms and microenvironmental cues that tune macrophage signaling in localized skin infection with the colonizing and opportunistic pathogen Staphylococcus aureus. Early in skin infection, the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by γδ T cells and hypoxic conditions within the dermal microenvironment diverted macrophages away from a homeostatic M-CSF- and hypoxia-inducible factor 1α (HIF-1α)-dependent program. This allowed macrophages to be metabolically rewired for maximal inflammatory activity, which requires expression of Irg1 and generation of itaconate, but not HIF-1α. This multifactorial macrophage rewiring program was required for both the timely clearance of bacteria and for the provision of local immune memory. These findings indicate that immunometabolic conditioning allows dermal macrophages to cycle between antimicrobial activity and protection against secondary infections.

Multilocus-sequence typing reveals clonality of Staphylococcus aureus in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is exacerbated by Staphylococcus aureus, which is capable of displacing not only the physiological microbiota, but also other strains of its own species. Analyses of the molecular characteristics and relationships of S. aureus strains present in different microniches are lacking. OBJECTIVES: To determine, using multilocus sequence typing (MLST), the relationship of S. aureus isolates from the lesional and nonlesional skin and anterior nares of patients with AD, and to review the characteristics of the dominant clones. METHODS: Sixty-three individuals with active AD were enrolled. Ten patients with moderate-to-severe AD (SCoring of Atopic Dermatitis score ≥ 25) colonized by S. aureus in all analysed locations were included in the MLST analysis. RESULTS: The most prevalent sequence types were 7 (10/30 strains; 33.3%), 15 and 97 (both 5/30 strains; 16.7%) all of which were associated with the expression of adhesins and toxins promoting chronic microbial dysbiosis, skin barrier damage and inflammation. Six patients (60%) were carriers of clonal S. aureus strains at all analysed locations, three (30%) carriers in lesional and nonlesional skin, and one (10%) was a carrier in nonlesional skin and the anterior nares. CONCLUSIONS: The results imply that the identified S. aureus lineages are better adapted to dominate the microbiota in AD. Decontaminating the identified reservoirs of S. aureus (i.e. anterior nares and nonlesional skin) could reduce the severity of AD.

An oral caspase inhibitor as monotherapy or with antibiotics eradicates MRSA skin infections in mice.

Staphylococcus aureus is the leading cause of skin and soft tissue infections. With the emergence of antibiotic-resistant bacteria, there is an unmet clinical need to develop immune-based therapies to treat skin infections. Previously, we have shown pan-caspase inhibition as a potential host-directed immunotherapy against community-acquired methicillin-resistant S aureus (CA-MRSA) and other bacterial skin infections. Here, we evaluated the role of irreversible pan-caspase inhibitor emricasan as a monotherapy and an adjunctive with a standard-of-care antibiotic, doxycycline, as potential host-directed immunotherapies against S. aureus skin infections in vivo. We used the established CA-MRSA strain USA300 on the dorsum of WT C57BL/6J mice and monitored lesion size and bacterial burden noninvasively, and longitudinally over 14 days with in vivo bioluminescence imaging (BLI). Mice in four groups placebo (0.5% carboxymethyl cellulose [CMC] solution), placebo plus doxycycline (100 mg/kg), emricasan (40 mg/kg) plus doxycycline, and emricasan only were treated orally twice daily by oral gavage for 7 days, starting at 4 h after injection of S aureus. When compared with placebo, all three groups, placebo plus doxycycline, emricasan plus doxycycline, and emricasan treated group, exhibited biological effect, with reduction of both the lesion size (*p = .0277, ****p < .0001, ****p < .0001, respectively) and bacterial burden (***p = .003, ****p < .0001, ****p < .0001, respectively). Importantly, the efficacy of emricasan against S. aureus was not due to direct antibacterial activity. Collectively, pan-caspase inhibitor emricasan and emricasan plus doxycycline reduced both the lesion size and bacterial burden in vivo, and emricasan is a potential host-directed immunotherapy against MRSA skin infections in a preclinical mouse model.

Progressão infantil de tinea capitis, kerion celsi e infecção secundária bacteriana cutânea com hemocultura positiva para s. Aureus ­ relato de caso / Infant progression of tinea capitis, kerion celsi and secondary bacterial skin infection with positive blood culture s. Aureus - case report

Introdução: A Tinea Capitis (TC) é uma dermatofitose que tem como evolução grave a forma Kerion Celsi (KC). Clinicamente, é caracterizada por manifestações tonsurantes e inflamatórias; diagnosticada por achados clínicos e laboratoriais, como micológico direto com KOH, tricoscopia e cultura fúngica. É utilizado no tratamento de TC antifúngicos sistêmicos por seis a oito semanas. Nesse caso houve associação de infecção secundária por Staphylococcus aureus, caracterizando um quadro atípico, raro. Objetivo: Relatar o caso, pouco descrito na literatura, de criança com Tinea Capitis (TC) com Kerion Celsi (KC) e bacteremia por contaminação secundária local e sistêmica de Staphylococcus aureus. Relato do caso: Paciente feminino, 5 anos, com manchas hiperemiadas, descamativas e pruriginosas de crescimento centrífugo em face, com surgimento de lesões circulares e pelos tonsurados em couro cabeludo que, após uso de antifúngico oral, houve inflamação aguda e saída de secreção. Apesar do tratamento independente domiciliar, com Betametasona e Cetoconazol creme e Cetoconazol 2% xampu, houve involução da lesão de face e ampliação da área de alopecia. Com a procura médica, iniciou tratamento sistêmico com Griseofulvina, seguido de antibioticoterapia oral por quadro bacteriano secundário em couro cabeludo. Houve linfonodomegalia cervical e intensificação do prurido e secreção. Foi internada para análise clínica e laboratorial, com antibioticoterapia endovenosa de amplo espectro: Ceftriaxona e Clindamicina. Colhida cultura da lesão e hemocultura, definiu-se, em ambas, S. aureus. Devido à resistência bacteriana, ocorreu troca para Cefazolina endovenosa. Na alta, a paciente seguiu com apoio dermatológico semanal e Griseofulvina, havendo a troca do antifúngico por Terbinafina. Conclusão: Quadro atípico e raro com progressão para bacteremia. O alerta para o diagnóstico precoce possibilita tratamento oral adequado e menor impacto da doença na qualidade de vida, evitando-se a contaminação secundária bacteriana

Introduction: Tinea Capitis (TC) is a dermatophytosis that has as severe evolution the form Kerion Celsi (KC). Clinically, it is characterized by tonsuring and inflammatory manifestations; diagnosed by clinical and laboratory findings, such as direct mycological with KOH, trichoscopy and fungal culture. It is used in the treatment of systemic antifungal CT for six to eight weeks. In this case there was an association of secondary infection by Staphylococcus aureus, characterizing an atypical, rare condition. Objective: To report the case, little described in the literature, of a child with Tinea Capitis (TC) with Kerion Celsi (KC) and bacteremia due to local and systemic secondary contamination of Staphylococcus aureus. Case report: Female patient, 5 years old, with hyperaemic, scaling and pruritic spots of centrifugal growth on the face, with the appearance of circular lesions and tonsure on the scalp that, after use of oral antifungal, there was acute inflammation and discharge of secretion. Despite the independent home treatment, with Betamethasone and Ketoconazole cream and Ketoconazole 2% shampoo, there was involution of the face injury and enlargement of the area of alopecia. With medical demand, he started systemic treatment with Griseofulvin, followed by oral antibiotic therapy for secondary bacterial condition in the scalp. There was cervical lymph node enlargement and intensification of pruritus and secretion. She was hospitalized for clinical and laboratory analysis, with broad spectrum intravenous antibiotic therapy: Ceftriaxone and Clindamycin. Culture of the lesion and blood culture, was defined in both S. aureus. Due to bacterial resistance, there was exchange for intravenous Cefazolin. At discharge, the patient followed with weekly dermatological support and Griseofulvin, with the exchange of antifungal by Terbinafine. Conclusion: Atypical and rare condition with progression to bacteremia. Early diagnosis provides adequate oral treatment and less impact of the disease on quality of life, avoiding secondary bacterial contamination

Introducción: La Tinea Capitis (TC) es una dermatofitosis cuya evolución severa es la forma Kerion Celsi (KC). Clínicamente se caracteriza por manifestaciones amigdalizantes e inflamatorias; se diagnostica por hallazgos clínicos y de laboratorio, como micología directa con KOH, tricoscopia y cultivo fúngico. Se utiliza en el tratamiento de la TC antifúngica sistémica durante seis a ocho semanas. En este caso se asoció infección secundaria por Staphylococcus aureus, caracterizando una condición atípica y rara. Objetivo: Reportar el caso, poco descrito en la literatura, de un niño con Tinea Capitis (TC) con Kerion Celsi (KC) y bacteriemia por contaminación secundaria local y sistémica de Staphylococcus aureus. Caso clínico: Paciente femenino, de 5 años de edad, con placas hiperémicas, descamativas y pruriginosas de crecimiento centrífugo en la cara, con aparición de lesiones circulares y pelo tonsurado en el cuero cabelludo que, luego de utilizar un antifúngico oral, presentó inflamación aguda y salida de secreciones. A pesar del tratamiento independiente domiciliario, con crema de Betametasona y Ketoconazol y shampoo de Ketoconazol al 2%, se presentó involución de la lesión facial y agrandamiento del área de alopecia. Con la búsqueda médica se inició tratamiento sistémico con Griseofulvina, seguido de antibioticoterapia oral por una afección bacteriana secundaria en el cuero cabelludo. Había agrandamiento de los ganglios linfáticos cervicales y aumento del prurito y la secreción. Ingresa para análisis clínicos y de laboratorio, con antibioticoterapia endovenosa de amplio espectro: Ceftriaxona y Clindamicina. Tras la recogida de cultivo de la lesión y hemocultivo, se definió S. aureus en ambos. Debido a la resistencia bacteriana, hubo un cambio a cefazolina intravenosa. Al alta, la paciente continuó con soporte dermatológico semanal y Griseofulvina, reemplazándose el antifúngico por Terbinafina. Conclusión: Condición atípica y rara con progresión a bacteriemia. La alerta para el diagnóstico precoz permite un adecuado tratamiento oral y menor impacto de la enfermedad en la calidad de vida, evitando contaminaciones bacterianas secundarias

The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections.

Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of Staphylococcus aureus (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyze not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient's condition and influence their recovery. In our work, we have tested if the treatment of normal human fibroblasts with staphylococcal phages will influence the metabolic state of the cell and the integrity of cell membranes. We have also analyzed the effectiveness of bacteriophages in reducing the number of MDRSA attached to human fibroblasts and the influence of the lytic activity of phages on cell viability. We observed that, out of three tested anti-Staphylococcal phages-vB_SauM-A, vB_SauM-C and vB_SauM-D-high concentrations (109 PFU/mL) of two, vB_SauM-A and vB_SauM-D, showed a negative impact on the viability of human fibroblasts. However, a dose of 107 PFU/mL had no effect on the metabolic activity or membrane integrity of the cells. We also observed that the addition of phages alleviated the negative effect of the MDRSA infection on fibroblasts' viability, as phages were able to effectively reduce the number of bacteria in the co-culture. We believe that these results will contribute to a better understanding of the influence of phage therapy on human cells and encourage even more studies on this topic.

Functionalized Rhodium Nanoparticles as Antimicrobial Agents for Treatment of Drug-Resistant Skin and Soft Tissue Infections.

Skin and soft tissue infections (SSTIs) are among the most common bacterial infections reported in outpatients. Drug-resistant bacteria are the major cause of treatment failure and increased mortality rate in patients with SSTIs, posing significant challenges to human health. In this study, new-generation rhodium nanoplates (RhNPs) and glycol chitosan- and polydopamine-functionalized RhNPs (Rh@GCS) are developed for the treatment of drug-resistant SSTIs. RhNPs exhibited favorable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Ag-resistant MRSA. The modified Rh@GCS exhibited enhanced antibacterial activity and can directly kill various drug-resistant bacteria by increasing the permeability of cell membranes, including gram-positive MRSA and gram-negative multidrug-resistant Escherichia coli (E.coli) and Pseudomonas aeruginosa (PA). Moreover, Rh@GCS effectively inhibited bacterial growth and promoted the healing of skin lesions in MRSA-induced SSTI mouse models. These results suggest that Rh@GCS is a promising nonantibiotic antimicrobial agent for the treatment of drug-resistant SSTIs.

Changing careers: Skin pathogen evolves to infect the bloodstream.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) rose to clinical dominance decades ago and predominantly manifested as skin and soft-tissue infections (SSTIs). These clones were distinct from those causing hospital acquired (HA-MRSA) infections. Dyzenhaus et al. describe the evolutionary changes necessary for CA-MRSA clones to cause bloodstream infections (BSIs).

Validation of a Clinical Decision Rule for Ultrasound Identification of MRSA Skin Abscesses in Children.

OBJECTIVE: The aim of this study was to validate an adult-derived clinical decision rule for ultrasound identification of methicillin-resistant Staphylococcus aureus (MRSA) skin abscesses in a pediatric cohort. METHODS: We conducted a retrospective study of skin and soft tissue infections in patients <21 years presenting to the emergency department who had radiology performed ultrasounds completed and wound cultures obtained. Ultrasound scans were reviewed for edge definition, volume, and shape by 2 pediatric emergency physicians with expertise in point-of-care ultrasound, with approximately 25% of scans reviewed by both experts to evaluate interrater reliability. A third, blinded expert weighed in for discrepancies before analysis. Test performance characteristics were calculated for the clinical decision rule in children. RESULTS: Two hundred nine patients were enrolled, with mean age of 9.8 (±6.7) years; 87 (42%) were male. Sixty-nine (33%) patients had a wound culture positive for MRSA. The clinical decision rule had a sensitivity of 86% (95% confidence interval [CI], 75%-93%), specificity of 32% (95% CI, 25%-41%), positive predictive value of 38% (95% CI, 35%-42%), negative predictive value of 82% (95% CI, 71%-89%), positive likelihood ratio of 1.26 (95% CI, 1.08-1.46), negative likelihood ratio of 0.45 (95% CI, 0.24-0.84), and an odds ratio of 2.8 (95% CI, 1.31-5.97). CONCLUSIONS: This clinical decision rule for ultrasound identification of MRSA abscesses had moderately high sensitivity and negative predictive value in pediatric patients, with similar sensitivity compared with the original adult validation group. Ultrasound may help identify MRSA abscesses, allowing for improved antibiotic choices and outcomes for children with MRSA abscesses.