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Science Translational Medicine Sep 2020Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety... (Randomized Controlled Trial)
Randomized Controlled Trial
Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by , cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.
Topics: Adult; Child; Dermatitis, Atopic; Eczema; Humans; Lipids; Methylobacteriaceae; Skin
PubMed: 32908007
DOI: 10.1126/scitranslmed.aaz8631 -
Acta Neurochirurgica Oct 2020Ventriculoperitoneal shunt (VPS) is an adequate treatment for congenital hydrocephalus or chronic hydrocephalus in adults. Yet, it is a surgery associated with a...
Ventriculoperitoneal shunt (VPS) is an adequate treatment for congenital hydrocephalus or chronic hydrocephalus in adults. Yet, it is a surgery associated with a significant rate of complications amongst neurosurgical procedures, with frequent shunt obstructions and infections. We report the first-ever case of peritonitis caused by Roseomonas mucosa, shortly after the revision of a VPS ventricular catheter. Hardware removal and proper antibiotic therapy led to the patient's recovery. Roseomonas mucosa is an opportunistic skin pathogen with an antibiotic resistance profile to many beta-lactamines and a tropism for indwelling catheters and post-operative period. Nowadays, it should be taken into account in case of infection of indwelling catheters and for some implantable medical devices.
Topics: Adult; Catheters, Indwelling; Humans; Hydrocephalus; Methylobacteriaceae; Peritonitis; Postoperative Complications; Prosthesis-Related Infections; Ventriculoperitoneal Shunt
PubMed: 32535796
DOI: 10.1007/s00701-020-04449-9 -
Journal of Infection and Chemotherapy :... Aug 2020Roseomonas, a genus of pink-pigmented glucose non-fermentative bacteria, has been associated with various primary and hospital-acquired human infections; however, to our...
Roseomonas, a genus of pink-pigmented glucose non-fermentative bacteria, has been associated with various primary and hospital-acquired human infections; however, to our knowledge, its nosocomial transmission has never been reported. Clinical and epidemiological investigations were carried out after two cases of R. mucosa bacteremia occurred in our hospital in 2018. Environmental samples were taken of environmental surfaces prone to water contamination in the wards and cultured. The two clinical isolates and all environmental isolates that showed growth of pink colonies were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry and 16S rRNA gene sequencing. Pulse-field gel electrophoresis (PFGE) was performed and fingerprinting software was used to analyze the DNA restriction patterns and determine their similarity. Two patients who developed R. mucosa bacteremia had received care from the same treatment team. Of 126 environmental samples, five showed growth of R. mucosa. Using 80% similarity as the cut-off, PFGE analysis revealed that the isolates from the two patients' blood cultures and three environmental isolates belonged to the same clone. The hospital water environment was contaminated with the same clone of R. mucosa that caused bacteremia in the two patients, suggesting nosocomial transmission linked to contaminated environment. Increased vigilance is needed to monitor the emergence of Roseomonas in healthcare settings.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cross Infection; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Fatal Outcome; Female; Gram-Negative Bacterial Infections; Hospitals; Humans; Methylobacteriaceae; RNA, Ribosomal, 16S; Sequence Analysis, RNA; Treatment Outcome; Waterborne Diseases
PubMed: 32265107
DOI: 10.1016/j.jiac.2020.03.007 -
Journal of Clinical Medicine Feb 2020Despite several methods having been described for disinfecting implants affected by periimplantitis, none of these are universally effective and may even alter surfaces...
Despite several methods having been described for disinfecting implants affected by periimplantitis, none of these are universally effective and may even alter surfaces and mechanical properties of implants. Boron-doped diamond (BDD) electrodes were fabricated from niobium wires and assembled as a single instrument for implant cleaning. Chemo-mechanical debridement and air abrasion were used as control methods. Different mono-species biofilms, formed by bacteria and yeasts, were allowed to develop in rich medium at 37 °C for three days. In addition, natural multi-species biofilms were treated. Implants were placed in silicone, polyurethane foam and bovine ribs for simulating different clinical conditions. Following treatment, the implants were rolled on blood agar plates, which were subsequently incubated at 37 °C and microbial growth was analyzed. Complete electrochemical disinfection of implant surfaces was achieved with a maximum treatment time of 20 min for , , , , and , while in case of spore-forming and , a number of colonies appeared after BDD electrode treatment indicating an incomplete disinfection. Independent of the species tested, complete disinfection was never achieved when conventional techniques were used. During treatment with BDD electrodes, only minor changes in temperature and pH value were observed. The instrument used here requires optimization so that higher charge quantities can be applied in shorter treatment times.
PubMed: 32050444
DOI: 10.3390/jcm9020475 -
American Journal of Clinical Dermatology Feb 2020The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use...
BACKGROUND
The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea.
OBJECTIVE
We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race.
METHODS
Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software.
RESULTS
Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%).
CONCLUSIONS
The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.
Topics: Adult; Aged; Bacteria; Case-Control Studies; Female; Humans; Male; Microbiota; Middle Aged; Rosacea; Skin; Young Adult
PubMed: 31502207
DOI: 10.1007/s40257-019-00471-5 -
Microbial Pathogenesis Sep 2019The bacterial species Roseomonas mucosa is pathogenic in humans, and although it is rarely detected during routine diagnostics, it is becoming increasingly important... (Comparative Study)
Comparative Study
The bacterial species Roseomonas mucosa is pathogenic in humans, and although it is rarely detected during routine diagnostics, it is becoming increasingly important clinically. For a long time, R. mucosa was regarded as a classic environmental bacterium. Recent studies, however, revealed that it is part of the physiological human skin flora and mainly affects immunocompromised patients. Furthermore, the use of catheter systems may increase the risk of contracting R. mucosa infections. The bacterium has been linked to severe infections, such as bacteraemia, osteomyelitis and cellulitis. Therefore, it is important to discern the best method of identifying R. mucosa in routine laboratory testing. To facilitate this testing, we compared three suitable methods for routine bacterial identification in the laboratory: VITEK 2, MALDI-TOF MS and 16S rRNA gene sequencing. Additionally, we conducted whole-genome sequencing (WGS) and calculated the average nucleotide identity (ANI). ANI is seen as the gold standard of strain identification; therefore, we decided to use it as a reference method. Both MALDI-TOF MS and 16S rRNA gene sequencing confidently identified the species. However, when using the VITEK 2 technique, isolates were misidentified as Roseomonas gilardii, Rhizobium radiobacter, or Sphingomonas paucimobilis. When conducting WGS and determining the ANI, it became obvious that one isolate belonged to the species R. gilardii rather than R. mucosa. Therefore (although not yet applicable in routine diagnostics), we suggest that WGS is presently the most appropriate technique to reliably identify Roseomonas mucosa. However, after expanding the Biotyper database, MALDI-TOF MS could also be an applicable method.
Topics: Adult; Aged; Bacterial Typing Techniques; Child, Preschool; Female; Humans; Infant; Male; Methylobacteriaceae; Middle Aged; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Whole Genome Sequencing; Young Adult
PubMed: 31185244
DOI: 10.1016/j.micpath.2019.103576 -
BMC Infectious Diseases Feb 2019Roseomonas mucosa, as a Gram-negative coccobacilli, is an opportunistic pathogen that has rarely been reported in human infections. Here we describe a case of bacteremia... (Review)
Review
BACKGROUND
Roseomonas mucosa, as a Gram-negative coccobacilli, is an opportunistic pathogen that has rarely been reported in human infections. Here we describe a case of bacteremia in an infective endocarditis patient with systemic lupus erythematosus (SLE).
CASE PRESENTATIONS
A 44-year-old female patient with SLE suffered bacteremia caused by Roseomonas mucosa complicated with infective endocarditis (IE). The patient started on treatment with piperacillin-tazobactam and levofloxacin against Roseomonas mucosa, which was switched after 4 days to meropenem and amikacin for an additional 2 weeks. She had a favorable outcome with a 6-week course of intravenous antibiotic therapy.
DISCUSSION AND CONCLUSIONS
Roseomonas mucosa is rarely reported in IE patients; therefore, we report the case in order to improve our ability to identify this pathogen and expand the range of known bacterial causes of infective endocarditis.
Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacteremia; Endocarditis; Endocarditis, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Lupus Erythematosus, Systemic; Methylobacteriaceae; Piperacillin, Tazobactam Drug Combination
PubMed: 30755159
DOI: 10.1186/s12879-019-3774-0 -
Frontiers in Cellular and Infection... 2018As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to...
As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to mucosal sites where they are not naturally found is of investigative interest. However, formal assessment of the toxicity potential of healthy skin commensal organisms has not been reported in the literature. Our previous research indicates that topical application of live to treat AD was associated with clinical benefit on the skin, but the effects of exposure via inhalation, eye inoculation, and ingestion were unknown. Herein we report our findings from mice inoculated with commensal strains of , coagulase negative (CNS), and . Bacterial isolates were collected under clinical trial NCT03018275, however these results do not represent an interventional clinical trial. Our tested R. mucosa isolates did not display significant infection or inflammation. However, neutropenic mice inoculated with CNS had infection without major inflammation in pulmonary models. In contrast, systemic infection generated hepatic and splenic pathology for and CNS, which was worsened by the presence of neutropenia. Our results suggest that LBP derived from bacteria without significant infectivity histories, such as , may represent safer options than known pathobionts like and spp. Overall, these results suggest that topically applied LBP from select skin commensals are likely to present safe therapeutic options and reinforce our prior clinical findings.
Topics: Animals; Bacterial Infections; Carrier State; Disease Models, Animal; Methylobacteriaceae; Mice; Probiotics; Pseudomonas aeruginosa; Staphylococcus; Symbiosis; Virulence
PubMed: 30719426
DOI: 10.3389/fcimb.2018.00451 -
IDCases 2018species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of bacteremia that...
species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be . The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory.
PubMed: 30479963
DOI: 10.1016/j.idcr.2018.e00469 -
The Journal of Allergy and Clinical... Jan 2019As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome... (Review)
Review
As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.
Topics: Adaptive Immunity; Dermatitis, Atopic; Female; Humans; Immunity, Innate; Male; Microbiota; Skin; Staphylococcal Skin Infections; Staphylococcus aureus
PubMed: 30476499
DOI: 10.1016/j.jaci.2018.11.015