Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection.

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

Acute myeloid leukaemia presenting with ecthyma gangrenosum as the first manifestation: A case report.

RATIONALE: Ecthyma gangrenosum (EG) is an uncommon cutaneous infection usually associated with Pseudomonas aeruginosa bacteremia in immunocompromised patients, particularly those with underlying malignant diseases. Despite its rarity, especially in immunocompetent or nondiagnosed immunodeficiency patients, EG can present as the first manifestation of an underlying immunosuppression. PATIENT CONCERNS: A 42-year-old Japanese man was admitted to our hospital with a 3-day history of a painless red macule on his right forearm and fever. DIAGNOSES: Blood culture on admission revealed the presence of Pseudomonas aeruginosa, whereas pus culture of the skin lesion showed Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus positivity. INTERVENTIONS: Additional bone marrow aspirate examination and immunophenotyping were performed to confirm the diagnosis of acute promyelocytic leukaemia with PML-retinoic acid alpha receptor. OUTCOMES: The patient was successfully treated with a 14-day course of antibiotics, and no evidence of relapse was noted. The patient achieved complete remission after treatment for acute promyelocytic leukaemia. LESSONS: It should be kept in mind that EG is an important cutaneous infection that is typically associated with P aeruginosa bacteremia and the presence of underlying immunodeficiency, such as acute leukaemia.

Community-genotype methicillin-resistant Staphylococcus aureus skin and soft tissue infections in Latin America: a systematic review

ABSTRACT Background: Community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) emerged in the 1990s as a global community pathogen primarily involved in skin and soft tissue infections (SSTIs) and pneumonia. To date, the CG-MRSA SSTI burden in Latin America (LA) has not been assessed. Objective: The main objective of this study was to report the rate and genotypes of community-genotype methicillin-resistant Staphylococcus aureus (CG-MRSA) causing community-onset skin and soft tissue infections (CO-SSTIs) in LA over the last two decades. In addition, this research determined relevant data related to SSTIs due to CG-MRSA, including risk factors, other invasive diseases, and mortality. Data sources: Relevant literature was searched and extracted from five major databases: Embase, PubMed, LILACS, SciELO, and Web of Science. Methods: A systematic review was performed, and a narrative review was constructed. Results: An analysis of 11 studies identified epidemiological data across LA, with Argentina presenting the highest percentage of SSTIs caused by CG-MRSA (88%). Other countries had rates of CG-MRSA infection ranging from 0 to 51%. Brazil had one of the lowest rates of CG-MRSA SSTI (4.5-25%). In Argentina, being younger than 50 years of age and having purulent lesions were predictive factors for CG-MRSA CO-SSTIs. In addition, the predominant genetic lineages in LA belonged to sequence types 8, 30, and 5 (ST8, ST30, and ST5). Conclusion: There are significant regional differences in the rates of CG-MRSA causing CO-SSTIs. It is not possible to conclude whether or not CG-MRSA CO-SSTIs resulted in more severe SSTI presentations or in a higher mortality rate.

Antibacterial photodynamic peptides for staphylococcal skin infection.

As the barrier between the human body and the outside world, the skin is vulnerable to pathogenic microorganisms, especially when suffering from skin injuries such as burns. Staphylococcus aureus remains the most common type of bacteria that infects humans, and the surging drug resistance poses a major threat to the treatment of these infections. Here we report the development of antibacterial photodynamic peptides (APPs) that are constructed based on the covalent conjugation of an antibacterial peptide and the photosensitizer chlorin e6 (Ce6). Peptide conjugation significantly increases the photo-stability of Ce6, while retaining its ROS generation capability under photo-irradiation. The APPs combine the antibacterial activity of the peptide and the photodynamic therapy of Ce6, and under the assistance of mild laser irradiation, can eradicate bacterial infection and inhibit the formation of bacterial biofilms ex vivo. One of the APPs, (GKRWWKWWRR)2KGGK(Ce6)G, AMP2-Ce6, with Ce6 conjugated with the dimeric peptide, showed exceptional antibacterial activity with an MIC90 value around 3.2 µM without photo-irradiation and <0.1 µM with short light treatment. Supported by a hydrogel matrix composed of gelatin and recombinant human collagen III protein (rhCol III) mimicking the extracellular matrix of skin cells, AMP2-Ce6 efficiently accelerated the healing rate of wounds and improved the quality of wound healing in mice infected with Staphylococcus aureus. Altogether, here we report the development of antibacterial photodynamic peptides, which together with a regenerative matrix material exhibit an added effect against staphylococcal skin infection. This composite material holds promise as a new type of wound dressing material for skin infection and wound healing.

An enzyme-responsive and photoactivatable carbon-monoxide releasing molecule for bacterial infection theranostics.

Infections caused by pathogenic bacteria, especially the drug-resistant bacteria, are posing a devastating threat to public health, which underscores the urgent needs for advanced strategies to effectively prevent and treat these intractable issues. Here we report a feasible and effective theranostic platform based on an enzyme-sensitive and photoactivatable carbon monoxide releasing molecule (CORM-Ac) for the successive detection and elimination of bacterial infection. The extracellular bacterial lipase can trigger the excited state intramolecular proton transfer (ESIPT) via elimination of the ester group in CORM-Ac, thus providing a fluorescence switch for an early warning of infection. Subsequently, the potent bactericidal therapy against the model bacterial strains, Staphylococcus aureus (S. aureus) and notorious methicillin-resistant Staphylococcus aureus (MRSA), was readily realized via photoinduced release of CO. In addition, the CORM-Ac and CORM showed good biocompatibility within a wide range of concentrations. The results of an infected animal wound test also demonstrated that the CORM-Ac-loaded gauze was effective in indicating the wound infection and accelerating the wound healing via the photoinduced CO release. The simplicity, functional integration, good biocompatibility and broad adaptability make CORM-Ac very attractive for bacterial theranostic applications.

Synergistic phage-surfactant combination clears IgE-promoted Staphylococcus aureus aggregation in vitro and enhances the effect in vivo.

Currently, topical antibiotic treatment is a major strategy for decolonisation of Staphylococcus aureus, although it may result in antibiotic resistance or recolonisation of the organism. Recently, application of bacteriophages in the treatment of S. aureus infection has attracted attention. However, a single administration of bacteriophages did not effectively decolonise S. aureus in our first trial in vivo. Using a bacteriophage (pSa-3) and surfactant combination in vitro, we showed an increased (>8%) adsorption rate of the bacteriophage on the host. Moreover, the combination increased the eradication of immunoglobulin E (IgE)-stimulated aggregation, as the surfactant promoted the dissociation of S. aureus aggregates by decreasing the size by 75% and 50% in the absence and presence of IgE, respectively. Furthermore, the combined treatment significantly decolonised the pathogen with an efficacy double that of the phage-only treatment, and decreased the expression of pro-inflammatory cytokine genes (IL-1ß, IL-12 and IFNγ) for 5 days in the second in vivo trial. These results suggest that the bacteriophage-surfactant combination could act as an alternative to antibiotics for S. aureus decolonisation in patients with dermatitis.

Peptides containing the PCNA interacting motif APIM bind to the ß-clamp and inhibit bacterial growth and mutagenesis.

In the fight against antimicrobial resistance, the bacterial DNA sliding clamp, ß-clamp, is a promising drug target for inhibition of DNA replication and translesion synthesis. The ß-clamp and its eukaryotic homolog, PCNA, share a C-terminal hydrophobic pocket where all the DNA polymerases bind. Here we report that cell penetrating peptides containing the PCNA-interacting motif APIM (APIM-peptides) inhibit bacterial growth at low concentrations in vitro, and in vivo in a bacterial skin infection model in mice. Surface plasmon resonance analysis and computer modeling suggest that APIM bind to the hydrophobic pocket on the ß-clamp, and accordingly, we find that APIM-peptides inhibit bacterial DNA replication. Interestingly, at sub-lethal concentrations, APIM-peptides have anti-mutagenic activities, and this activity is increased after SOS induction. Our results show that although the sequence homology between the ß-clamp and PCNA are modest, the presence of similar polymerase binding pockets in the DNA clamps allows for binding of the eukaryotic binding motif APIM to the bacterial ß-clamp. Importantly, because APIM-peptides display both anti-mutagenic and growth inhibitory properties, they may have clinical potential both in combination with other antibiotics and as single agents.

Antimicrobial and anti-inflammatory potential of Angelica dahurica and Rheum officinale extract accelerates wound healing in Staphylococcus aureus-infected wounds.

Wound infection is a serious clinical problem, and the most common infection-causing bacteria are Staphylococcus aureus and Pseudomonas aeruginosa. Angelica dahurica and Rheum officinale extract (ARE) was reported to accelerate excisional wound healing in rats. In this study, we investigated the therapeutic effects of ARE on bacterial-infected wounds. Thirty Sprague-Dawley rats were divided into three groups: normal saline (NS), ARE, and biomycin ointment (BO). Full-thickness dorsal excisions in all the rats were infected with 108 colony-forming units of S. aureus; the treatments were applied once daily for 7 days. Results showed that the residual wound area in ARE group was smaller than those in NS and BO groups. TBCs on wound sites gradually decreased in ARE and BO groups. The body temperature and plasma inflammatory cytokines (TNF-α, IL-6) levels increased after bacterial infection at 24 h in all groups. After treatment, BT and inflammatory cytokines levels decreased in ARE group. Histological observations showed ARE group exhibited earlier scab formation, denser dermal granulation tissue, thicker epidermis, and more angiogenesis markers than the other groups. In conclusion, ARE accelerated wound healing in S. aureus-infected wounds. We proposed ARE exhibited potential antimicrobial and anti-inflammatory effects and stimulated angiogenesis, thus improving healing in infected wounds.

New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection.

Dalbavancin is an effective antibiotic that is widely used to treat skin infection. Our aim was to determine the effect of dalbavancin administration on wound healing compared to that of vancomycin and to elucidate if epidermal growth factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), MMP-9, and vascular endothelial growth factor (VEGF) could be involved in its therapeutic mechanism. A mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection was established. Mice were treated daily with vancomycin (10 mg/kg) and weekly with dalbavancin at day 1 (20 mg/kg) and day 8 (10 mg/kg). After 14 days, wounds were excised, and bacterial counts were performed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbavancin and vancomycin are effective in reducing the bacterial load in wounds. The dalbavancin group showed a strong effect compared with infected untreated animals and the vancomycin-treated group. The wounds treated with dalbavancin showed robust epidermal coverage with reconstitution of the regular and keratinized epidermal lining and well-organized granulation tissue with numerous blood vessels, although slightly less than that in the uninfected group. While in the vancomycin-treated group the epithelium appeared, in general, still hypertrophic, the granulation tissue appeared even less organized. We observed elevated EGFR and VEGF expression in both treated groups, although it was higher in dalbavancin-treated mice. MMP-1 and MMP-9 were decreased in uninfected tissue and in both treated tissues compared with untreated infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with higher EGFR and VEGF levels.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in erythrodermic cutaneous T-cell lymphoma (CTCL) patients.

Erythroderma can occur in cutaneous T-cell lymphoma (CTCL). Staphylococcus aureus (S. aureus) prevalence is increased in CTCL patients and contributes to CTCL disease flares. Our primary aim was to describe S. aureus infections, including resistance patterns and the antibiotic treatment regimens used, in erythrodermic CTCL patients. This was a retrospective chart review of erythrodermic CTCL patients who had S. aureus infection or colonization and were treated at the UT MD Anderson Cancer Center's Melanoma Skin Center between 2012 and 2016. Twenty-six erythrodermic CTCL patients had 50 documented S. aureus colonization or infection events. Patients had an improvement in body surface area (BSA) or modified Severity Weighted Assessment Tool (mSWAT) in 53% events treated for S. aureus. Seventeen of the 50 (34%) events were due to methicillin-resistant S. aureus (MRSA). One-third (33%) of MRSA events were initially treated with dicloxacillin. The MRSA isolates were sensitive to trimethoprim-sulfamethoxazole (92%) and doxycycline (88%). Patients treated in the outpatient setting (OR 0.073; 95% CI 0.008-0.627; p = 0.017) and patients with a previous history of topical anti-S. aureus decolonization treatments before S. aureus event as stand-alone (OR 0.125; 95% CI 0.018-0.887; p = 0.038) or in combination treatment with systemic antibiotics (OR 0.094; 95% CI 0.009-0.944; p = 0.045) were less likely to see improvement in BSA or mSWAT from S. aureus treatment. Treatment of S. aureus improved CTCL skin score in a high number of erythrodermic patients. The MRSA prevalence was high in erythrodermic CTCL patients. Clinicians should consider using empiric MRSA antibiotic coverage for these patients.

Microbiologic characteristics and antibiotic resistance rates of diabetic foot infections / Perfil microbiológico e de resistência bacteriana no pé diabético infectado

ABSTRACT Purpose: the purpose of this research was to identify the sociodemographic and microbiological characteristics and antibiotic resistance rates of patients with diabetic foot infections, hospitalized in an emergency reference center. Methods: it was an observational and transversal study. The sociodemographic data were collected by direct interview with the patients. During the surgical procedures, specimens of tissue of the infected foot lesions were biopsied to be cultured, and for bacterial resistance analysis. Results: the sample consisted of 105 patients. The majority of patierns were men, over 50 years of age, married and with low educational level. There was bacterial growth in 95 of the 105 tissue cultures. In each positive culture only one germ was isolated. There was a high prevalence of germs of the Enterobacteriaceae family (51,5%). Gram-negative germs were isolated in 60% of cultures and the most individually isolated germs were the Gram-positive cocci, Staphylococcus aureus (20%) and Enterococcus faecalis (17,9%). Regarding antibiotic resistance rates, a high frequency of Staphylococcus aureus resistant to methicillin (63,0%) and to ciprofloxacin (55,5%) was found; additionally, 43,5% of the Gram-negative isolated germs were resistant to ciprofloxacin. Conclusions: the majority of patients were men, over 50 years of age, married and with low educational level. The most prevalent isolated germs from the infected foot lesions were Gram-negative bacteria, resistant to ciprofloxacin, and the individually most isolated germ was the methicillin resistant Staphylococcus aureus.

RESUMO Objetivo: identificar o perfil sociodemográfico, microbiológico e de resistência bacteriana em pacientes com pé diabético infectado. Métodos: tratou-se de estudo observacional, transversal que avaliou os perfis sóciodemográfico e microbiológico de pacientes portadores de pé diabético infectado internados em Pronto Socorro de referência. Os dados sociodemográficos foram coletados por meio de entrevista. Foram colhidos, durante os procedimentos cirúrgicos, fragmentos de tecidos das lesões podais infectadas para realização de cultura/antibiograma. Resultados: a amostra foi composta por 105 pacientes. O perfil sociodemográfico mais prevalente foi o de pacientes do sexo masculino, acima dos 50 anos, casados e com baixa escolaridade. Das 105 amostras de fragmentos de tecidos colhidos para realização de cultura e antibiograma, 95 foram positivas, com crescimento de um único germe em cada um dos exames. Houve predomínio de germes da família Enterobacteriaceae (51,5%). Germes Gram-negativos foram isolados em 60,0% das culturas e os espécimes mais isolados individualmente foram os cocos Gram-positivos, Staphylococcus aureus (20,0%) e Enterococcus faecalis (17,9%). Considerando-se os perfis de resistência bacteriana, verificou-se alta taxa de Staphylococcus aureus resistente à meticilina (63,0%) e à ciprofloxacino (55,5%); verificou-se, também, que 43,5% dos germes Gram-negativos eram resistentes à ciprofloxacino. Conclusões: o perfil sociodemográfico majoritário, foi o de homens, com mais de 50 anos e com baixa escolaridade. Concluímos que os germes mais prevalentes nas lesões podais dos pacientes diabéticos foram os Gram-negativos, resistentes ao ciprofloxacino e que o germe mais isolado individualmente foi o Staphylococcus aureus resistente à meticilina.

Short tryptophan- and arginine-rich peptide shows efficacy against clinical methicillin-resistant Staphylococcus aureus strains isolated from skin and soft tissue infections.

In recent years methicillin-resistant Staphylococcus aureus has posed a challenge in treating skin and soft tissue infections. Finding new antimicrobial agents has therefore become imperative. We evaluated the in vitro antimicrobial activity of a synthetic peptide, P6, against multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. The P6 antimicrobial effect was evaluated in vitro by determining MIC/MBC, the ratio of live/dead cells and the effects induced at membrane level. The therapeutic efficiency was determined against human skin cells. P6 inhibited growth for all strains between 8 and 16 mg/L and killed all bacterial strains at 16 mg/L. The therapeutic potential was found to be 30 and 15 in the presence of BSA. We showed that P6 localizes at membrane level, where it acts slowly, by depolarizing it and affecting its integrity. P6 can be considered a good candidate for use as an antimicrobial agent in topical applications.

The bactericidal effect of lysostaphin coupled with liposomal vancomycin as a dual combating system applied directly on methicillin-resistant Staphylococcus aureus infected skin wounds in mice.

BACKGROUND AND AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of surgical infection, and its resistance to numerous conventional antibiotics makes treatment difficult. Although vancomycin is often an effective agent for the initial therapy of MRSA, clinical failure sometimes occurs. Therefore, there is an urgent need to develop better therapies. Here, we prepared some vancomycin-loaded nanoliposomes coupled with anti-staphylococcal protein (lysostaphin) and evaluated their in vitro and in vivo efficacy as a topical MRSA therapy. METHODS: Vancomycin was encapsulated in liposomes, and the coupling of lysostaphin with the surface of liposomes was carried out through cyanuric functional groups. The bactericidal efficacies and a full characterization were evaluated. To define different nanoliposomal-bacterium interactions and their bactericidal effect, flow cytometry was employed. Finally, in vivo, the topical antibacterial activity of each formulation was measured against surgical wound MRSA infection in a mouse model. RESULTS: High encapsulation and conjugation efficiency were achieved for all formulations. All the formulations showed a significant reduction in bacterial counts (p<0.05). The targeted liposomes more effectively suppress bacterial infection in vitro and in vivo relative to equivalent doses of untargeted vancomycin liposome. The flow cytometry results confirmed liposome-bacterium interactions, which increased during the incubation time. The maximum binding rate and the bactericidal effect were significantly higher in targeted liposomes (p<0.05) compared with control liposomes. CONCLUSION: Our data suggest a novel nano-vehicle (lysostaphin-conjugated coupled liposomal vancomycin) which could be used as a great topical antimicrobial construct for treatment of MRSA skin infections.

Early switch/early discharge opportunities for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Brazil

ABSTRACT Background: Early antibiotic switch and early discharge protocols have not been widely studied in Latin America. Our objective was to describe real-world treatment patterns, resource use, and estimate opportunities for early switch from intravenous to oral antibiotics and early discharge for patients hospitalized with methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections. Materials/methods: This retrospective medical chart review recruited 72 physicians from Brazil to collect data from patients hospitalized with documented methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections between May 2013 and May 2015, and discharged alive by June 2015. Data collected included clinical characteristics and outcomes, hospital length of stay, methicillin-resistant Staphylococcus aureus-targeted intravenous and oral antibiotic use, and early switch and early discharge eligibility using literature-based and expert-validated criteria. Results: A total of 199 patient charts were reviewed, of which 196 (98.5%) were prescribed methicillin-resistant Staphylococcus aureus -active therapy. Only four patients were switched from intravenous to oral antibiotics while hospitalized. The mean length of methicillin-resistant Staphylococcus aureus-active treatment was 14.7 (standard deviation, 10.1) days, with 14.6 (standard deviation, 10.1) total days of intravenous therapy. The mean length of hospital stay was 22.2 (standard deviation, 23.0) days. The most frequent initial methicillin-resistant Staphylococcus aureus-active therapies were intravenous vancomycin (58.2%), intravenous clindamycin (19.9%), and intravenous daptomycin (6.6%). Thirty-one patients (15.6%) were discharged with methicillin-resistant Staphylococcus aureus -active antibiotics of which 80.6% received oral antibiotics. Sixty-two patients (31.2%) met early switch criteria and potentially could have discontinued intravenous therapy 6.8 (standard deviation, 7.8) days sooner, and 65 patients (32.7%) met early discharge criteria and potentially could have been discharged 5.3 (standard deviation, 7.0) days sooner. Conclusions: Only 2% of patients were switched from intravenous to oral antibiotics in our study while almost one-third were early switch eligible. Additionally, one-third of hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections were early discharge eligible indicating opportunity for reducing intravenous therapy and days of hospital stay. These results provide insight into possible benefits of implementation of early switch/early discharge protocols in Brazil.

An unusual deep fungal infection with Nigrospora sphaerica in HIV positive patient.

A 34-year-old HIV positive male with a CD4+ cell count of 133 cell/mm3 presented with multiple crusted and hemorrhagic ulcers on the face, scalp, trunk, and limbs for 3 months. Skin biopsies showed granulomatous inflammation with microabscesses and lots of hyphae and spores. PCR identified the fungus as Nigrospora sphaerica. This is mainly a plant pathogen which rarely causes opportunistic infections in humans. After a thorough literature search we found very few reported cases of human infection by this fungus worldwide but none in Africa. We therefore report the first case of human infection by Nigrospora sphaerica in the African continent.

Multifunctional Delivery Nanosystems Formed by Degradable Antibacterial Poly(Aspartic Acid) Derivatives for Infected Skin Defect Therapy.

Nucleic acid (NA)-based therapy is promising for tissue repair, such as skin and bone defect therapy. However, bacterial infections often occur in the process of tissue healing. The ideal treatment of tissue repair requires both anti-infection and simultaneous tissue healing. The epidermal growth factor (EGF) plays an important role in wound healing processes. In this work, degradable antibacterial gene vectors based on tobramycin (clinically relevant antibiotic) conjugated poly(aspartic acid) (TPT) are proposed as multifunctional delivery nanosystems of plasmid encoding EGF (pEGF) to realize the antibacterial therapy and tissue healing of infected skin defects. TPT has low cytotoxicity and good degradability, which is helpful in the NA delivery process. TPT demonstrates good transfection performances and hemocompatibility, as well as excellent antibacterial activities in vitro. The outstanding pEGF delivery ability of TPT and the bioactivity of expressed EGF facilitate the proliferation of fibroblast cells. The effective in vivo infected skin defect therapy is also demonstrated with TPT/pEGF nanocomplexes, where skin tissue healing is promoted. The present work opens new avenues for the design of multifunctional delivery nanosystems with antibacterial ability to treat infected tissue defect.

Aurein-Derived Antimicrobial Peptides Formulated with Pegylated Phospholipid Micelles to Target Methicillin-Resistant Staphylococcus aureus Skin Infections.

Antimicrobial peptides have been the focus of considerable research; however, issues associated with toxicity and aggregation have the potential to limit clinical applications. Here, a derivative of a truncated version of aurein 2.2 (aurein 2.2Δ3), namely peptide 73, was investigated, along with its d-amino acid counterpart (D-73) and a retro-inverso version (RI-73). A version that incorporated a cysteine residue to the C-terminus (73c) was also generated, as this form is required to covalently attach antimicrobial peptides to polymers (e.g., polyethylene glycol (PEG) or hyperbranched polyglycerol (HPG)). The antimicrobial activity of the 73-derived peptides was enhanced 2- to 8-fold, and all the derivatives eradicated preformed Staphylococcus aureus biofilms. Formulation of the peptides with compatible polyethylene glycol (PEG)-modified phospholipid micelles alleviated toxicity toward human cells and reduced aggregation. When evaluated in vivo, the unformulated d-enantiomers aggregated when injected under the skin of mice, but micelle encapsulated peptides were well absorbed. Pegylated micelle formulated peptides were investigated for their potential as therapeutic agents for treating high-density infections in a murine cutaneous abscess model. Formulated peptide 73 reduced abscess size by 36% and bacterial loads by 2.2-fold compared to the parent peptide aurein 2.2Δ3. Micelle encapsulated peptides 73c and D-73 exhibited superior activity, further reducing abscess sizes by 85% and 63% and lowering bacterial loads by 510- and 9-fold compared to peptide 73.

Clinical and microbiological properties of Staphylococcus lugdunensis skin infections.

Staphylococcus lugdunensis is an emerging pathogen in skin and soft tissue infections that was previously considered a commensal. The aim of this study was to elucidate the characteristics of skin infections by S. lugdunensis and its appropriate management, in a tertiary referral medical center. The clinical files, bacterial cultures and histopathology reports of all S. lugdunensis isolates from skin infections over a period of 8 years (September 2009-September 2017) were reviewed. S. lugdunensis was isolated from 29 patients with skin infections, aged 7-89 years (mean 33.3 years). A state of immune suppression (drug-induced, malignancy or diabetes) was present in five patients (17%). Folliculitis and cutaneous pustulosis were the most common presentations (16 cases, 55%), followed by secondary infection of hidradenitis suppurativa (five cases, 17%). Other sources of isolation were infected molluscum contagiosum (two cases), folliculitis decalvans (one case), dissecting cellulitis (one case), abscess (one case), cyst (one case), impetigo (one case) and granuloma after trauma (one case). The in vitro antibiotic sensitivity tests showed susceptibility to most tested antibiotics, although a few isolates were resistant to gentamycin, penicillin and oxacillin. In 19 of 20 patients for whom follow ups were available, cutaneous manifestations improved or resolved with proper local and/or oral antibiotic therapy. S. lugdunensis may play a role as a primary or secondary pathogen in various skin infections, most commonly folliculitis and pustulosis. Proper antibiotic therapy may lead to improvement or resolution.

Coagulase-Negative Staphylococcus Skin and Soft Tissue Infections.

Coagulase-negative staphylococcus organisms may be normal flora of human skin, however these bacteria can also be pathogens in skin and soft tissue infections. A summary of skin and soft tissue infections caused by coagulase-negative staphylococcus species is provided in this review. We conducted a search of the PubMed database using the following terms: abscess, auricularis, biofilm, capitis, cellulitis, coagulase, contaminant, cyst, draining, epidermidis, felon, folliculitis, furuncle, haemolyticus, hominis, indolent, infection, lugdunensis, mecA, microbiome, negative, osteomyelitis, paronychia, saprophyticus, skin, simulans, sinus, soft, staphylococcus, systemic, tissue, virulence, virulent, and vulvar. The relevant papers, and their references, generated by the search were reviewed. Skin and soft tissue infections have been observed to be caused by many coagulase-negative staphylococcus organisms: Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus saprophyticus, and Staphylococcus simulans. Coagulase-negative staphylococcus skin infections predominantly present as abscesses and paronychia. They are most common in elderly patients or those individuals who are immunosuppressed, and tend to be broadly susceptible to antibiotic treatment. In conclusion, albeit less common, coagulase-negative staphylococcus organisms can result in skin and soft tissue infections, particularly in older and/or immunocompromised individuals. A review of the literature found that coagulase-negative staphylococcus organisms are most commonly grown in cultures of abscesses and paronychia. Therefore, coagulase-negative staphylococcal organisms should not always be considered as contaminants or normal flora, but rather as causative pathogens. They are usually susceptible to antibiotics used to treat methicillin-sensitive Staphylococcus aureus.