Stenotrophomonas maltophilia skin infection in an immunocompetent patient: Primary cutaneous CD30+ T-cell lymphoproliferative disorder or pseudolymphoma?

Cutaneous pseudolymphomas are a wide group of diseases mimicking cutaneous lymphoma. They comprise several skin conditions with different etiopathogenesis, clinical-pathological features, and prognosis, which may occur in the absence of an identifiable trigger factor or after administration of medications or vaccinations, tattoos, infections, or arthropod bites. They present with different manifestations: from solitary to regionally clustered lesions, up to generalized distribution and, in rare cases, erythroderma. They persist variably, from weeks to years, and resolve spontaneously or after antibiotics, but may recur in some cases. CD30+ T-cell pseudolymphomas are characterized by the presence of large, activated lymphoid cells, generally in response to viral infections, arthropod assault reactions, and drug eruptions. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacillus responsible for opportunistic infections in immunocompromised patients. Infection of intact skin in immunocompetent patients is particularly rare. Here, we report a case of a man presenting an isolated nodule histopathologically mimicking a primary cutaneous CD30+ T-cell lymphoproliferative disorder.

Systemic Bacterial Infection in a Captive Agouti (Dasyprocta leporina Linnaeus, 1758).

The agouti (Dasyprocta leporina) is a neotropical rodent which has the potential to be domesticated. As such, some research studies have been done on the biology of this animal. Recently, these animals are being kept in captivity as a source of animal protein. Animals which are kept in captivity may present diseases that would not have been reported in the wild due to lack of observation or the lack of occurrence. The aim of this short communication is to report a case of systemic bacterial infection that affected the lungs and liver of a captive agouti. Bacterial analysis revealed that the infection was caused by Escherichia coli. Bacterial infections have been reported in the mammary tissue as well as the skin of the agouti, but to the authors' knowledge, this is the first report of systemic infection in the agouti affecting several organs. This case was seen in a nine-month-old male agouti that was being housed at the University of the West Indies Field Station (UWI, UFS). The animal showed no apparent sign of disease except for lethargy and subsequently died before any treatment was administered. These findings showed that the agouti may have been under some stress (nutritional or environmental) which predisposed this animal to this infection. Future work has to address the nutritional requirements for the growing agouti as well as some treatment options for managements of similar cases in the future.

Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach.

Pseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.

Skin abscesses, X-linked agammaglobulinaemia and spastic paraplegias in a male patient.

We report a patient with X-linked agammaglobulinaemia and spastic paraplegias who developed skin abscesses. We highlight that dermatologists should consider the possibility of primary immunodeficiency when patients present with repeated skin infections, and should advise patients to be particularly careful about skin hygiene and avoid scratching.

The Correlations between Clinical Features, Dermoscopic and Histopathological Findings, and Treatment Outcomes of Patients with Pitted Keratolysis.

BACKGROUND: Pitted keratolysis (PK) is a superficial bacterial infection diagnosed mainly by clinical manifestations. Current data on its dermoscopic and histopathological findings, and the correlation of those findings, are limited. OBJECTIVES: To evaluate the clinical manifestations, dermoscopic, and histopathological findings of PK and to determine the correlations. METHODS: Forty naval cadets with PK and five cadets with normal feet were enrolled this cohort study and provided informed consent. Dermoscopy was independently applied and evaluated by 2 dermatologists. Shave biopsies were performed on 37 patients with PK. RESULTS: Pits were the most common dermoscopic finding (88.1%). The dermoscope had more sensitivity for the detection of PK than the naked eye examinations. Apart from the pits and the presence of bacteria, the most common histopathological finding for PK was color alteration of keratin. The presence of bacteria correlated with interrupted dermatoglyphic lines and the color alteration of keratin. Moreover, the presence of bacteria at the base of pits was related to worse treatment outcomes. CONCLUSIONS: Dermoscopy is a useful tool for PK diagnosis. Color alteration of keratin is another histopathological finding for PK. The presence of bacteria is associated with worse treatment outcomes.

Bioinspired Multifunctional Cellulose Nanofibril-Based In Situ Liquid Wound Dressing for Multiple Synergistic Therapy of the Postoperative Infected Wound.

A smart in situ-formed wound dressing with excellent antibacterial ability against drug-resistance bacterial, antitumor, and biofilm-eliminating activities to promote effective wound closure is highly desirable in therapeutic and clinical applications. Herein, we designed and developed a multifunctional; shape-adaptable; and pH, temperature, and near-infrared radiation (NIR) multiple responsive cellulose nanofibril (CNF)-based in situ liquid wound dressing, using a pH-sensitive CNF grafted with terminated amino hyperbranched polyamines (HBP-NH2) as a substrate, along with poly(N-isopropylacrylamide) and indocyanine green (ICG) loaded as the temperature and NIR on/off switches, respectively. The 3D nanocage network structure of CNF and the nanocavities in the hyperbranched structure of HBP-NH2 endow the dressing with a high loading capacity for active drugs (doxorubicin and ICG) simultaneously. Moreover, the responsiveness of the dressing to multiple stimuli enables controllable and efficient drug release to the wound area. The bioinspired dressing demonstrates excellent antibacterial activity against common bacteria and methicillin-resistant Staphylococcus aureus, antitumor activity against A375 tumor cells, and biofilm-eliminating capability. In addition, the developed dressing synergistically combines multiple therapeutic strategies for effective wound healing, specifically photothermal therapy, photodynamic therapy, and chemotherapy. The design provides an ideal clinical intervention strategy for irregular tumor postoperative infected wounds.

Autophagy as a Target for Drug Development Of Skin Infection Caused by Mycobacteria.

Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.

ε­Polylysine-stabilized agarose/polydopamine hydrogel dressings with robust photothermal property for wound healing.

Polydopamine (PDA) is emerging as an attractive photothermal agent due to its good photothermal performance and excellent biocompatibility. However, without chemical modification, PDA is normally unstable and usually leached out from the constructed biomaterials, realistically limiting its application space. Here, we constructed a new hydrogel dressing with robust and stable photothermal performance by introduction of ε-Polylysine (ε-PL) into agarose/PDA matrix to efficiently lock PDA. By optimizing PDA/ε-PL rational dose in agarose network structure, a hybrid agarose/PDA/ε-PL hydrogel (ADPH) with stable photothermal functionality and desirable physicochemical properties could be achieved. ADPH possessed satisfactory microbicidal efficacy in vivo, which enabled the bacteria-infected skin wound to be cured quickly by successful suppressing inflammation, accelerating collagen deposition and promoting angiogenesis in a bacterial-infected wound model. Collectively, this study illustrates a simple, convenient but powerful strategy to design functionally stable ADPH dressing for treating dermal wounds, which could open vistas in clinical wound management.

Optogenetic Modification of Pseudomonas aeruginosa Enables Controllable Twitching Motility and Host Infection.

Cyclic adenosine monophosphate (cAMP) is an important secondary messenger that controls carbon metabolism, type IVa pili biogenesis, and virulence in Pseudomonas aeruginosa. Precise manipulation of bacterial intracellular cAMP levels may enable tunable control of twitching motility or virulence, and optogenetic tools are attractive because they afford excellent spatiotemporal resolution and are easy to operate. Here, we developed an engineered P. aeruginosa strain (termed pactm) with light-dependent intracellular cAMP levels through introducing a photoactivated adenylate cyclase gene (bPAC) into bacteria. On blue light illumination, pactm displayed a 15-fold increase in the expression of the cAMP responsive promoter and an 8-fold increase in its twitching activity. The skin lesion area of nude mouse in a subcutaneous infection model after 2-day pactm inoculation was increased 14-fold by blue light, making pactm suitable for applications in controllable bacterial host infection. In addition, we achieved directional twitching motility of pactm colonies through localized light illumination, which will facilitate the studies of contact-dependent interactions between microbial species.

Staphylococcus aureus impairs cutaneous wound healing by activating the expression of a gap junction protein, connexin-43 in keratinocytes.

Chronic wounds have been considered as major medical problems that may result in expensive healthcare. One of the common causes of chronic wounds is bacterial contamination that leads to persistent inflammation and unbalanced host cell immune responses. Among the bacterial strains that have been identified from chronic wounds, Staphylococcus aureus is the most common strain. We previously observed that S. aureus impaired mouse cutaneous wound healing by delaying re-epithelialization. Here, we investigated the mechanism of delayed re-epithelialization caused by S. aureus infection. With the presence of S. aureus exudate, the migration of in vitro cultured human keratinocytes was significantly inhibited and connexin-43 (Cx43) was upregulated. Inhibition of keratinocyte migration by S. aureus exudate disappeared in keratinocytes where the expression of Cx43 knocked down. Protein kinase phosphorylation array showed that phosphorylation of Akt-S473 was upregulated by S. aureus exudate. In vivo study of Cx43 in S. aureus-infected murine splinted cutaneous wound model showed upregulation of Cx43 in the migrating epithelial edge by S. aureus infection. Treatment with a PI3K/Akt inhibitor reduced Cx43 expression and overcame the wound closure impairment by S. aureus infection in the mouse model. This may contribute to the development of treatment to bacterium-infected wounds.

Mycobacterium marinum: nodular hand lesions after a fishing expedition.

Mycobacterium marinum is a slow-growing, acid-fast bacillus in the category of non-tuberculous mycobacteria which most commonly cause skin and soft tissue infections in patients, particularly those with aquatic exposure. Classically, M. marinum skin and soft tissue infections clinically manifest with formation of nodular or sporotrichoid extremity lesions, or deeper space infections such as tenosynovitis and osteomyelitis. Disseminated disease may occur in immunocompromised hosts. M. marinum is a slow-growing organism that is challenging to culture, as it typically requires 5-14 days (yet may take up to several weeks) with low temperatures of approximately 30°C to yield growth. In terms of treatment, further data are needed to elucidate the optimal regimen and duration for M. marinum infections. Combination therapy with clarithromycin and ethambutol is recommended for treatment of skin and soft tissue infections, with addition of rifampicin for deeper space infections. Surgery may be needed in addition to medical management.

Graphene Oxide/Copper Nanoderivatives-Modified Chitosan/Hyaluronic Acid Dressings for Facilitating Wound Healing in Infected Full-Thickness Skin Defects.

PURPOSE: Wound healing, especially of infected wounds, remains a clinical challenge in plastic surgery. This study aimed to manufacture a novel and multifunctional wound dressing by combining graphene oxide/copper nanocomposites (GO/Cu) with chitosan/hyaluronic acid, providing significant opportunities for the therapy of wound repair in wounds with a high risk of bacterial infection. METHODS: In this study, GO/Cu-decorated chitosan/hyaluronic acid dressings (C/H/GO/Cu) were prepared using sodium trimetaphosphate (STMP) crosslinking and the vacuum freeze-drying method, and chitosan/hyaluronic acid dressings (C/H) and GO-incorporated chitosan/hyaluronic acid dressings (C/H/GO) served as controls. The surface characterization, in vitro degradation under various pH values, antimicrobial potential, cytocompatibility and in vivo therapeutic efficacy in a bacteria-infected full-thickness skin defect model were systematically evaluated. RESULTS: Our experimental results indicated that the acidic environment facilitated the release of copper (CuNPs and Cu2+) from the dressings, and prepared C/H/GO/Cu dressings exhibited significant in vitro antimicrobial activities against the two tested bacterial strains (ATCC35984 and ATCC25923). All three dressings showed satisfactory cytocompatibility with mouse fibroblasts (NIH/3T3-L1). Moreover, remarkably accelerated wound healing was found in the C/H/GO/Cu group, with controlled inflammatory infiltration and improved angiogenesis in granulation tissues. In addition, no pathological damage was noted in the tissue structures of the tested organs (heart, lung, liver and kidney) in any of the four groups. CONCLUSION: Collectively, GO/Cu-incorporated chitosan/hyaluronic acid dressings suggested a synergistic antimicrobial efficacy and acceptable biocompatibility both in vitro and in vivo, as well as a significantly accelerated healing process of bacteria-infected wounds. Thus, the multifunctional C/H/GO/Cu composite is expected to be a potential alternative for wound dressings, especially for the management of intractable wounds caused by bacterial infection.

Linezolid as a treatment option for cutaneous non-tuberculous mycobacterial infections.

Cutaneous non-tuberculous mycobacterial (NTM) infections have rapidly increased in incidence in recent years. Currently there is no standard treatment and the variable and nonspecific ways in which cutaneous NTM infection presents makes it a therapeutic and diagnostic challenge. We describe a 67-year-old immunocompetent woman with cutaneous NTM infection after she recently underwent a root canal procedure. Although the species was not identified and she was unable to tolerate multiple antibiotics, she ultimately responded well to three months of treatment with linezolid. Given that cutaneous NTM infection can present in immunocompetent patients and that the incidence is rising, it is important for clinicians to maintain a high index of clinical suspicion, especially in patients with a recent history of surgery, trauma, or cosmetic procedures. Linezolid has coverage against non-tuberculous mycobacteria and is an effective therapeutic option for cutaneous NTM cases in which identification to the species level is not possible or when adverse effects limit therapeutic options.

[A woman with nodules on her arm]. / Een vrouw met bultjes op haar arm.

A 73 year old female presented with five non-painful nodules on the dorsal side of her right lower arm that occured after an infection on her third digit finger after cleaning her aquarium. PCR of the biopsy from on of the nodules shows a mycobacterium marinum infection.