RESUMO
The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile.
Assuntos
Antibacterianos/farmacologia , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Plasmídeos/genética , Vancomicina/farmacologia , Animais , Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Modelos Animais de Doenças , Farmacorresistência Bacteriana/genética , Vida Livre de Germes , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Plasmídeos/isolamento & purificação , Vancomicina/uso terapêutico , Sequenciamento Completo do GenomaRESUMO
INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.
Assuntos
Doença de Crohn/complicações , Doenças da Vulva/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Vulva/diagnóstico , Doenças da Vulva/terapia , Adulto JovemRESUMO
Clostridioides difficile infection (CDI) is the leading cause of health care-associated infections in the United States. The increasing incidence and recurrence rates of CDI together with its associated morbidity and mortality are great concerns. Newer treatment methods, such as narrow-spectrum antibiotics, monoclonal antibodies, and microbial replacement therapies, are being developed and implemented. We searched PubMed to identify published literature from 2010 to 2018 using the following keywords: Clostridium difficile, treatment, and therapy. Cited references were also used to identify relevant literature. This review focuses on the current standard of therapy and emerging therapies for CDI and summarizes the updated guidelines on treatment of CDI.
Assuntos
Clostridioides difficile , Infecções por Clostridium/terapia , Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Transplante de Microbiota Fecal , Humanos , Probióticos/uso terapêutico , RecidivaRESUMO
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
Assuntos
Disbiose/microbiologia , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/metabolismo , Intestino Delgado/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , DNA Bacteriano/isolamento & purificação , Fibras na Dieta/administração & dosagem , Açúcares da Dieta/efeitos adversos , Disbiose/dietoterapia , Disbiose/tratamento farmacológico , Disbiose/fisiopatologia , Feminino , Gastroenteropatias/dietoterapia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/fisiopatologia , Voluntários Saudáveis , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/fisiopatologia , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Permeabilidade , Projetos Piloto , Adulto JovemRESUMO
BACKGROUND: Conflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development. METHODS: We conducted a retrospective, case-control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age- and sex-matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date. RESULTS: Three hundred ninety-nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non-SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05-2.93). CONCLUSIONS: Our findings support an increased risk of SCC development in the setting of AD.