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.

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.

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.

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

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).

Rapid diagnostics for skin and soft tissue infections: the current landscape and future potential.

PURPOSE OF REVIEW: Managing antimicrobial therapy in patients with complicated skin and soft tissue infections (SSTI) constitutes a growing challenge due to the wide spectrum of potential pathogens and resistance phenotypes. Today, microbiological documentation relies on cultural methods. This review summarizes the available evidence regarding the clinical input of rapid microbiological diagnostic tools (RMDT) and their impact on the management of antimicrobial therapy in SSTI. RECENT FINDINGS: Accurate tools are already available for the early detection of methicillin-resistant Staphylococcus aureus (MRSA) in SSTI samples and may help avoiding or shortening empirical anti-MRSA coverage. Further research is necessary to develop and evaluate RMDT detecting group A streptococci (e.g., antigenic test) and Gram-negative pathogens (e.g., multiplex PCR assays), including through point-of-care utilization. Next-generation sequencing (NGS) methods could provide pivotal information for the stewardship of antimicrobial therapy, especially in case of polymicrobial or fungal SSTI and in the immunocompromised host; however, a shortening in the turnaround time and prospective data regarding their therapeutic input are needed to better appraise the clinical positioning of these promising approaches. SUMMARY: The clinical input of RMDT in SSTI is currently limited due to the scarcity of available dedicated assays and the polymicrobial feature of certain cases. NGS appears as a relevant tool but requires further developments before its implementation in routine clinical practice.

Skin and soft tissue infections in the elderly.

PURPOSE OF REVIEW: To highlight the peculiarity of skin and soft tissue infections (SSTIs) in elderly patients and to provide useful elements for their optimal management. RECENT FINDINGS: In the COVID-19 era, early discharge from the hospital and implementation of outpatient management is of key importance. SUMMARY: Elderly patients are at high risk of SSTIs due to several factors, including presence of multiple comorbidities and skin factors predisposing to infections. Clinical presentation may be atypical and some signs of severity, such as fever and increase in C-reactive protein, may be absent or aspecific in this patients population. An appropriate diagnosis of SSTIs in the elderly is crucial to avoid antibiotic overtreatment. Further studies should explore factors associated with bacterial superinfections in patients with pressure ulcers or lower limb erythema. Since several risk factors for methicillin-resistant Staphylococcus aureus (MRSA) may coexist in elderly patients, these subjects should be carefully screened for MRSA risk factors and those with high risk of resistant etiology should receive early antibiotic therapy active against MRSA. Physicians should aim to several objectives, including clinical cure, patient safety, early discharge and return to community. SSTIs in the elderly may be managed using long-acting antibiotics, but clinical follow-up is needed.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

Does a Positive Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screen Predict the Risk for MRSA Skin and Soft Tissue Infection?

BACKGROUND: Skin and soft tissue infections (SSTIs) are often caused by gram-positive bacteria that colonize the skin. Given the overuse of antibiotics, SSTIs are increasingly caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Guidance on the utility of MRSA nasal screening for MRSA SSTI is limited. OBJECTIVE: To determine whether MRSA nasal screening predicts the risk of MRSA SSTIs. METHODS: This was a single-center, retrospective cohort study of adult patients with an SSTI diagnosis that had MRSA nasal screening and wound cultures obtained within 48 hours of starting antibiotics. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated using VassarStats. Pretest and posttest probabilities were estimated with Microsoft Excel. RESULTS: A total of 884 patient encounters were reviewed between December 1, 2018, and October 31, 2021, and 300 patient encounters were included. The prevalence of MRSA SSTI was 18.3%. The MRSA nasal colonization had a sensitivity of 63.6%, specificity of 93.9%, positive predictive value of 70.0% (95% CI = 55.2%-81.7%), negative predictive value of 92.0% (95% CI = 87.7%-94.9%), positive likelihood ratio of 10.39 (95% CI = 6.12-17.65), negative likelihood ratio of 0.39 (95% CI = 0.27-0.55), positive posttest probability of 70.0%, and negative posttest probability of 8.0%. CONCLUSIONS: Given the high positive likelihood ratio, a positive MRSA nasal screen was associated with a large increase in the probability of MRSA SSTI at our institution, and a negative MRSA nasal screen was associated with a small but potentially significant decrease in the probability of MRSA SSTI.

Frequency and Antibiotic Susceptibility Pattern of Community-associated Methicillin-resistant Staphylococcus Aureus (CA-MRSA) in Uncomplicated Skin and Soft Tissue Infections.

OBJECTIVE: To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021. METHODOLOGY: Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed. RESULTS: A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin. CONCLUSION: The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections. KEY WORDS: Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

Rifampicin treatment of canine multidrug-resistant meticillin-resistant staphylococcal pyoderma: A retrospective study of 51 cases.

BACKGROUND: Rifampicin (RFP) is a potential treatment for canine multidrug-resistant (MDR) meticillin-resistant staphylococci (MRS), yet the use of lower doses based on recent MIC data has not been evaluated in vivo. HYPOTHESIS/OBJECTIVES: To provide information on the efficacy and safety of low-dose range RFP (≤6 mg/kg/day) for the treatment of canine MDR MRS pyoderma. ANIMALS: Fifty-one client-owned dogs. MATERIALS AND METHODS: Retrospective review of dogs medical records. Dogs were from 11 US dermatology referral practices and had oral RFP at ≤6 mg/kg/day. Data evaluated included response to treatment, adverse events, and serum changes in alanine aminotransferase (ALT) and alkaline phosphatase (ALP). RESULTS: Complete resolution of pyoderma occurred in 39 of 51 dogs (76.5%). Topical antimicrobials were used concurrently in most cases (47 of 51; 92.2%). ALP elevation >1.5-fold of baseline or the high end of the reference range occurred in nine of 37 (24.3%) dogs, while ALT elevation above baseline and the high end of the reference range occurred in two of 36 (5.6%). Only six of 51 (11.8%) had clinical adverse events during treatment; five of six (83.3%) were mild reactions consisting of lethargy and gastrointestinal signs, while one dog had a possible cutaneous adverse drug reaction. Of those that experienced clinical adverse events, four of six (66.7%) did not have concurrent increased liver enzyme activity, while two of six (33.3%) had elevations in ALP alone. CONCLUSIONS AND CLINICAL RELEVANCE: Low-dose RFP (≤6 mg/kg/day) appears to be a relatively safe and effective single-agent systemic antibiotic in combination with topical antimicrobials for canine MDR MRS pyoderma.

CONTEXTE: La rifampicine (RFP) est un traitement potentiel des staphylocoques canins multirésistants (MDR) résistants à la méticilline (MRS), mais l'utilisation de doses plus faibles sur la base de données récentes sur la CMI n'a pas été évaluée in vivo. Hypothèse/Objectifs : Fournir des informations sur l'efficacité et l'innocuité des RFP à faible dose (≤ 6 mg/kg/jour) pour le traitement de la pyodermite MDR-MR canine. Animaux : Cinquante et un chiens de propriétaires. Matériels et méthodes : Revue rétrospective de chiens ayant reçu RFP par voie orale à des doses ≤ 6 mg/kg/jour provenant des dossiers médicaux de 11 centres de référés en dermatologie aux États-Unis. Les données évaluées comprenaient la réponse au traitement, les événements indésirables et les modifications sériques de l'alanine aminotransférase (ALT) et de la phosphatase alcaline (ALP). Résultats : Une résolution complète de la pyodermite s'est produite chez 39 des 51 chiens (76,5 %). Des antimicrobiens topiques ont été utilisés simultanément dans la plupart des cas (47 sur 51 ; 92,2 %). Une élévation de l'ALP> 1,5 fois la ligne de base ou l'extrémité supérieure de la plage de référence s'est produite chez neuf des 37 (24,3%) chiens, tandis qu'une élévation de l'ALT au-dessus de la ligne de base et de l'extrémité supérieure de la plage de référence s'est produite chez deux des 36 (5,6%). Seuls six sur 51 (11,8 %) ont eu des événements indésirables cliniques pendant le traitement ; cinq des six (83,3 %) étaient des réactions bénignes consistant en une léthargie et des signes gastro-intestinaux, tandis qu'un chien a eu un possible effet indésirable cutané au médicament. Parmi ceux qui ont subi des événements indésirables cliniques, quatre sur six (66,7 %) n'ont pas eu d'augmentation simultanée de l'activité des enzymes hépatiques, tandis que deux sur six (33,3 %) ont présenté des élévations de l'ALP seule. Conclusions et pertinence clinique : La RFP à faible dose (≤ 6 mg/kg/jour) semble être un antibiotique systémique à agent unique relativement sûr et efficace en association avec des antimicrobiens topiques pour la pyodermite MDR MRS canine.

Introducción- la rifampicina (RFP) es un tratamiento potencial para los estafilococos resistentes a múltiples fármacos (MDR) y meticilina (MRS), sin embargo, el uso de dosis más bajas basado en datos recientes de MIC no se ha evaluado in vivo. Hipótesis/Objetivos- Proporcionar información sobre la eficacia y seguridad de RFP en el rango de dosis bajas (≤6 mg/kg/día) para el tratamiento de la pioderma canina MDR MRS. Animales- Cincuenta y un perros propietarios particulares. Materiales y métodos- revisión retrospectiva de perros que recibieron RFP oral a dosis ≤6 mg/kg/día obtenida de historiales clínicos de 11 prácticas de referencia de dermatología de los Estados Unidos. Los datos evaluados incluyeron la respuesta al tratamiento, los eventos adversos y los cambios séricos en la alanina aminotransferasa (ALT) y la fosfatasa alcalina (ALP). Resultados- una resolución completa de la pioderma ocurrió en 39 de 51 perros (76,5 %). Antimicrobianos tópicos se usaron al mismo tiempo en la mayoría de los casos (47 de 51; 92,2%). En nueve de 37 (24,3 %) perros se produjo una elevación de ALP >1,5 veces respecto al valor inicial o el extremo superior del rango de referencia, mientras que en dos de 36 (5,6 %) se produjo una elevación de ALT por encima del valor inicial y en el límite superior del rango de referencia. Solo seis de 51 (11,8%) tuvieron eventos adversos clínicos durante el tratamiento; cinco de seis (83,3 %) fueron reacciones leves que consistieron en letargo y signos gastrointestinales, mientras que un perro tuvo una posible reacción cutánea adversa al medicamento. De los que experimentaron eventos adversos clínicos, cuatro de seis (66,7 %) no tuvieron un aumento simultáneo de la actividad de las enzimas hepáticas, mientras que dos de seis (33,3 %) tuvieron elevaciones en la ALP por sí sola. Conclusiones y relevancia clínica- la dosis baja de RFP (≤6 mg/kg/día) parece ser un antibiótico sistémico de uso único relativamente seguro y efectivo en combinación con antimicrobianos tópicos para la pioderma canina MDR MRS.

Contexto - A rifampicina (RFP) é um tratamento potencial para estafilococos resistentes à meticilina (MRS) multirresistentes (MDR) e a utilização de doses mais baixas baseado em dados recentes de MIC não foi avaliada in vivo. Hipótese/Objetivos: Fornecer informações sobre a eficácia e segurança de RFP em menor dosagem (≤6 mg/kg/dia) para o tratamento de piodermite canina por MRS MDR. Animais: Cinquenta e um cães de clientes. Materiais e métodos: Uma revisão retrospectiva dos prontuários de cães que receberam RFP oral na dose de ≤6 mg/kg/dia em 11 clínicas dermatológicas nos Estados Unidos. Os dados avaliados incluíram resposta ao tratamento, eventos adversos, alterações séricas de alanina aminotransferase (ALT) e fosfatase alcalina (FA). Resultados: Resolução completa da piodermite ocorreu em 39 de 51 dos cães (76,5%). Antimicrobianos tópicos foram utilizados concomitantemente na maioria dos casos (47 de 51; 92,2%). Elevação de mais de 1,5 vezes na FA ou para o limite superior do intervalo de referência ocorreu em nove de 37 cães (24,3%), enquanto a elevação de ALT acima do valor inicial e o limite superior do valor de referência ocorreu em dois de 36 (5,6%). Apenas cinco de 51 (11,8%) apresentaram efeitos adversos durante o tratamento; cinco de seis (83,3%) tiveram reações leves caracterizadas por letargia e sinais gastrointestinais, enquanto um cão apresentou uma possível farmacodermia. Dos que apresentaram eventos adversos, quatro de seis (66,7%) não apresentaram aumento concomitante de enzimas hepáticas, enquanto dois de seis (33,3%) tiveram aumento de FA isoladamente. Conclusões e relevância clínica - RFP em baixa dosagem (≤6 mg/kg/dia) aparenta ser relativamente segura e eficaz em monoterapia no tratamento da piodermite canina por MRS MDR por via sistêmica, associada a antimicrobianos tópicos.

Cyclic-di-GMP stimulates keratinocyte innate immune responses and attenuates methicillin-resistant Staphylococcus aureus colonization in a murine skin wound infection model.

BACKGROUND: Staphylococcus aureus is a leading cause for morbidity and mortality associated with skin and burn wound infections. Therapeutic options for methicillin-resistant S. aureus (MRSA) have dwindled and therefore alternative treatments are urgently needed. In this study, the immuno-stimulating and anti-MRSA effects of cyclic di-guanosine monophosphate (c-di-GMP), a uniquely bacterial second messenger and immuno-modulator, were investigated in HaCaT human epidermal keratinocytes and a murine skin wound infection model. RESULTS: Stimulation of HaCaT cells with 125 µM c-di-GMP for 12 h prior to MRSA challenge resulted in a 20-fold reduction in bacterial colonization compared with untreated control cells, which was not the result of a direct c-di-GMP toxic effect, since bacterial viability was not affected by this dose in the absence of HaCaT cells. C-di-GMP-stimulated or MRSA-challenged HaCaT cells displayed enhanced secretion of the antimicrobial peptides human ß-defensin 1 (hBD-1), hBD-2, hBD-3 and LL-37, but for hBD1 and LL-37 the responses were additive in a c-di-GMP-dose-dependent manner. Secretion of the chemokines CXCL1 and CXCL8 was also elevated after stimulation of HaCaT cells with lower c-di-GMP doses and peaked at a dose of 5 µM. Finally, pre-treatment of mice with a 200 nmol dose of c-di-GMP 24 h before a challenge with MRSA in skin wound infection model resulted in a major reduction (up to 1,100-fold by day 2) in bacterial CFU counts recovered from challenged skin tissue sections compared PBS-treated control animals. Tissue sections displayed inflammatory cell infiltration and enhanced neutrophil influx in the c-di-GMP pre-treated animals, which might account for the reduced ability of MRSA to colonize c-di-GMP pre-treated mice. CONCLUSIONS: These results demonstrate that c-di-GMP is a potent immuno-modulator that can stimulate anti-MRSA immune responses in vivo and might therefore be a suitable alternative prophylactic or therapeutic agent for MRSA skin or burn wound infections.

Impact of MRSA polymerase chain reaction (PCR) wound swabs on antibiotic de-escalation in skin and soft tissue infections.

Methicillin-resistant strains of S. aureus (MRSA) polymerase chain reaction (PCR) testing is a laboratory test that allows for rapid detection of MRSA and is available to use in skin infections via wound swab. There are limited data demonstrating the utility of MRSA PCR wound swabs on clinical outcomes in skin and soft tissue infections. This retrospective, single-center study included 652 patients to determine if the use of a MRSA PCR wound swab in skin infections results in a more rapid de-escalation in antibiotics. Patients with a MRSA PCR negative wound swab demonstrated a 1.0 (-1.5 to -0.53) day reduction of anti-MRSA antibiotic usage compared to those in the control group who did not have a MRSA PCR available (wound culture data only) (P < 0.001, unadjusted). The results of this study demonstrate that MRSA PCR wound swab assays have the potential to play a significant role in antibiotic de-escalation in the setting of skin and soft tissue infections.

Nanobased Antibacterial Drug Discovery to Treat Skin Infections of Staphylococcus aureus Using Moringa oleifera-Assisted Zinc Oxide Nanoparticle and Molecular Simulation Study.

In addition to the physical barrier, the epidermis acts as a natural barrier against microbial proliferation. It is prone to bacterial infections on the skin and in the nose, such as Staphylococcus aureus, as well as a variety of other skin illnesses. Green nanomaterial production, which eliminates the use of harmful chemicals while simultaneously reducing time, is gaining popularity in the nanotechnology area. Using the leaf extract of the pharmacologically valuable plant Moringa oleifera, we described a green synthesis of ZnO NPs (zinc oxide nanoparticles). ZnO NPs had a particle size of 201.6 nm and a zeta potential of -56.80 mV, respectively. A novel aminoketone antibacterial medication was synthesized and tested for antibacterial activity using ZnO NPs as a phytocatalyst in this work. This method produces high yields while maintaining efficient and gentle reaction conditions. Moringa oleifera extract can reduce ZnO to ZnO NPs in a straightforward manner. FT-IR, 1H-NMR, 13C-NMR, mass spectra, elemental analysis, and morphological analysis were used to synthesize and describe the antibacterial medicines (1a-1g) and (2a-2g). In addition, antibacterial activity was evaluated against bacteria such as Enterococcus faecalis and Staphylococcus aureus, and compound 1c (63 µg/mL, E. faecalis) and compound 2e (0.12 µg/mL, S. aureus) were found to be very active when compared to other medications. mupirocin is used as a reference. In addition, studies of in silico molecular docking for the bacterial DsbA protein were conducted. The strong molecules 1c (-4.3 kcal/mol) and 2e (-5.1 kcal/mol) exhibit a high binding affinity through hydrogen bonding, according to docking tests.

Cationic amphiphilic dendrons with effective antibacterial performance.

Bacterial infections and antibiotic resistance have become a global healthcare crisis. Herein, we designed and synthesized a series of cationic amphiphilic dendrons with cationic dendrons and hydrophobic alkyl chains for potential antibacterial applications. Our results showed that the antimicrobial activities of the cationic amphiphilic dendrons were highly dependent upon the length of the hydrophobic alkyl chain, whereas the number of cationic charges was less important. Among these cationic amphiphilic dendrons, a prime candidate was identified, which possessed excellent antimicrobial activity against various pathogens (minimum inhibitory concentrations of 9, 3, and 3 µg mL-1 for Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, respectively). Scanning electron microscopy and fluorescence microscopy analyses showed that it could disrupt the integrity of a pathogen's membrane, leading to cell lysis and death. In addition, in vitro bacteria-killing kinetics showed that it had rapid bactericidal efficiency. It also had excellent antimicrobial activities against MRSA in vivo and promoted wound healing. In general, the synthesized cationic amphiphilic dendrons, which exhibited rapid and broad-spectrum bactericidal activity, may have great potential in antimicrobial applications.

Plasmonic Nanozymes: Localized Surface Plasmonic Resonance Regulates Reaction Kinetics and Antibacterial Performance.

Among the members of the rapidly growing nanozyme family, plasmonic nanozymes stand out because of their unique localized surface plasmon resonance (LSPR) characteristics and tunable catalytic activity. We prepared a plasmonic nanozyme of Au gold nanoparticles (AuNPs) and Cu metal-organic framework nanosheets (Cu-MOFNs). The Cu-MOFNs have peroxidase-like activity, while AuNPs present unique LSPR characteristics. We found that the as-prepared AuNPs/Cu-MOFNs composite presents 1.6-fold faster reaction kinetics under LSPR excitation compared to that in the dark. Investigations of energy levels, radical capture, and dark-field scattering spectroscopy revealed that LSPR of AuNPs as well as matched energy levels can facilitate efficient hot electron transfer, which could readily cleave the chemical bond of the substrate and accelerate the reaction kinetics. On the basis of these results, we achieved enhanced antibacterial therapy and wound healing using plasmonic AuNPs/Cu-MOFNs. This study spotlights the superiority of plasmonic nanozymes in improving the enzyme-like performance of nanozymes.

Photonic Hydrogels for Synergistic Visual Bacterial Detection and On-Site Photothermal Disinfection.

Rapid and sensitive diagnostics in the early stage of bacterial infection and immediate treatment play critical roles in the control of infectious diseases. However, it remains challenging to develop integrated systems with both rapid detection of bacterial infection and timely on-demand disinfection ability. Herein, we demonstrate a photonic hydrogel platform integrating visual diagnosis and on-site photothermal disinfection by incorporating Fe3O4@C nanoparticles into a poly(hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAAm) matrix. In vitro experiments demonstrate that such a hydrogel can respond to pH variation caused by bacterial metabolism and generate the corresponding color changes to realize naked-eye observation. Meanwhile, its excellent photothermal conversion ability enables it to effectively kill bacteria by destroying cell membranes under near-infrared irradiation. Moreover, the pigskin infection wound model also verifies the bacterial detection performance and disinfection ability of the hydrogel in vivo. Our strategy demonstrates a new approach for visual diagnosis and treatment of bacterial infections.