RESUMEN
INTRODUCTION: Pectins have anti-inflammatory properties on intestinal immunity through direct interactions on Toll-like receptors (TLRs) in the small intestine or via stimulating microbiota-dependent effects in the large intestine. Both the degree of methyl-esterification (DM) and the distribution of methyl-esters (degree of blockiness; DB) of pectins contribute to this influence on immunity, but whether and how the DB impacts immunity through microbiota-dependent effects in the large intestine is unknown. Therefore, this study tests pectins that structurally differ in DB in a mouse model with Citrobacter rodentium induced colitis and studies the impact on the intestinal microbiota composition and associated attenuation of inflammation. METHODS AND RESULTS: Both low and high DB pectins induce a more rich and diverse microbiota composition. These pectins also lower the bacterial load of C. rodentium in cecal digesta. Through these effects, both low and high DB pectins attenuate C. rodentium induced colitis resulting in reduced intestinal damage, reduced numbers of Th1-cells, which are increased in case of C. rodentium induced colitis, and reduced levels of GATA3+ Tregs, which are related to tissue inflammation. CONCLUSION: Pectins prevent C. rodentium induced colonic inflammation by lowering the C. rodentium load in the caecum independently of the DB.
Asunto(s)
Colitis/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Pectinas/química , Pectinas/farmacología , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Ciego/efectos de los fármacos , Ciego/metabolismo , Citrobacter rodentium/patogenicidad , Citrus sinensis/química , Colitis/microbiología , Colitis/patología , Citocinas/metabolismo , Infecciones por Enterobacteriaceae/patología , Ésteres/química , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Ratones Endogámicos C57BL , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/patologíaRESUMEN
Irritable bowel syndrome (IBS) is a chronic intestinal disorder accompanied by low-grade inflammation, visceral hypersensitivity, and gut microbiota dysbiosis. Several studies have indicated that Lactobacillus supplementation can help to alleviate IBS symptoms and that these effects are strain-specific. Therefore, this study aimed to investigate the key physiological characteristics and functional genes contributing to the IBS-alleviating effects of Lactobacillus. An IBS model was established by subjecting C57BL/6 mice to Citrobacter rodentium ingestion and water avoidance stress. Lactobacillus strains with different physiological characteristics were administered to mice intragastrically for 4 weeks (5 × 109 CFU/0.2 mL per mouse per day). Indicators of colonic inflammation, visceral hypersensitivity, and gut microbiota were also evaluated. Finally, differences in functional genes between Lactobacillus strains were analyzed by a comparative genomic analysis, and the relationships between the physiological characteristics, functional genes, and IBS-alleviating effects of the strains were quantified using correlation analysis. Among the eight tested Lactobacillus strains, only Lactobacillus plantarum CCFM8610 significantly inhibited the expression of IL-1ß, IL-6, PAR-2, and mast cell tryptase. L. plantarum CCFM8610 also significantly increased the intestinal barrier function, inhibited visceral hypersensitivity symptoms, and modulated the gut microbiota diversity and composition. The correlation analysis of factors associated with the IBS-alleviating effects of Lactobacillus revealed the ability to synthesize conjugated linoleic acid as the most strongly associated physiological characteristic and COG1028-related genes as the most strongly associated functional genes. In conclusion, these findings can facilitate the rapid screening of Lactobacillus strains with IBS-alleviating effects and lay a foundation for studies of the related mechanisms.
Asunto(s)
Síndrome del Colon Irritable/microbiología , Lactobacillus/genética , Probióticos/farmacología , Animales , Citrobacter rodentium , Colon/microbiología , Colon/patología , Corticosterona/sangre , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Humanos , Inflamación/patología , Inflamación/prevención & control , Lactobacillus/fisiología , Ácidos Linoleicos Conjugados , Masculino , Ratones , Ratones Endogámicos C57BL , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Triptasas/metabolismoRESUMEN
Decreases in short-chain-fatty-acids (SCFAs) are linked to inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious colitis, treatment with Pectin and Tributyrin diets reduced the severity of colitis by restoring Firmicutes and Bacteroidetes and by increasing mucus production. RNA-seq in young adult mouse colon (YAMC) cells identified higher expression of Lgr4, Lgr6, DCLK1, Muc2, and SIGGIR after Butyrate treatment. Lineage tracing in CR-infected Lgr5-EGFP-IRES-CreERT2/ROSA26-LacZ (Lgr5-R) mice also revealed an expansion of LacZ-labeled Lgr5(+) stem cells in the colons of both Pectin and Tributyrin-treated mice compared to control. Interestingly, gut microbiota was required for Pectin but not Tributyrin-induced Lgr5(+) stem cell expansion. YAMC cells treated with sodium butyrate exhibited increased Lgr5 promoter reporter activity due to direct Butyrate binding with Lgr5 at -4.0 Kcal/mol, leading to thermal stabilization. Upon ChIP-seq, H3K4me3 increased near Lgr5 transcription start site that contained the consensus binding motif for a transcriptional activator of Lgr5 (SPIB). Thus, a multitude of effects on gut microbiome, differential gene expression, and/or expansion of Lgr5(+) stem cells seem to underlie amelioration of colitis following dietary intervention.
Asunto(s)
Colitis/microbiología , Colitis/patología , Dieta , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Microbiota , Células Madre/patología , Animales , Biodiversidad , Butiratos/farmacología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Citrobacter rodentium/fisiología , Epitelio/patología , Fermentación , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Ratones Endogámicos C57BL , Mucina 2/metabolismo , Pectinas/farmacología , Regiones Promotoras Genéticas/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Regeneración/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Triglicéridos/farmacologíaRESUMEN
Enteropathogenic and enterohemorrhagic Escherichia coli are important enteric pathogens that induce hemorrhagic colitis or even fatal hemolytic uremic syndrome. Emerging evidence shows that some bio-actives derived from fruits and vegetables may serve as alternatives to antibiotics for overcoming multidrug resistant E. coli infections. In this study, the Citrobacter rodentium (Cr) infection model was utilized to mimic E. coli-induced acute intestinal inflammation, and the effects of a cruciferous vegetable-derived cancer protective compound, indole-3-carbinol (I3C), on the immune responses of Cr-susceptible C3H/HeN mice were investigated. Dietary I3C significantly inhibited the loss of body weight and the increase in spleen size in Cr infected mice. In addition, I3C treatment reduced the inflammatory response to Cr infection by maintaining anti-inflammatory cytokine IL-22 mRNA levels while reducing expression of other pro-inflammatory cytokines including IL17A, IL6, IL1ß, TNF-α, and IFN-γ. Moreover, the serum cytokine levels of IL17, TNF-α, IL12p70, and G-CSF also were down-regulated by I3C in Cr-infected mice. Additionally, dietary I3C specifically enhanced the Cr-specific IgG response to Cr infection. In general, dietary I3C reduced the Cr-induced pro-inflammatory response in susceptible C3H/HeN mice and alleviated the physiological changes and tissue damage induced by Cr infection but not Cr colonization.
Asunto(s)
Antibacterianos , Antiinflamatorios , Brassicaceae/química , Citrobacter rodentium , Suplementos Dietéticos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/inmunología , Inmunoglobulina G/inmunología , Indoles/administración & dosificación , Fitoterapia , Esplenomegalia/tratamiento farmacológico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/patología , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/patología , Indoles/aislamiento & purificación , Indoles/farmacología , Mediadores de Inflamación/metabolismo , Interleucinas/metabolismo , Masculino , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Esplenomegalia/etiología , Esplenomegalia/patología , Interleucina-22RESUMEN
BACKGROUND: Over the past decade, drug resistance pattern has worsened for many of the uropathogens due to overuse of antibiotics for empiric treatment. The burden of extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae associated urinary tract infections (UTI) has become increasingly more common, limiting treatment options among children presenting with febrile UTI. We investigated the burden and correlates of ESBL producing Enterobacteriaceae associated UTI among children and antibacterial resistance pattern. METHODS: 284 midstream urine specimens were collected using standard aseptic techniques from 284 children who were diagnosed with suspected UTI. Urine culture and bacteria isolation were performed following standard bacteriological techniques. The Kirby-Bauer disk diffusion technique and the double-disc synergy test were used to investigate antibiotic susceptibility and presence of ESBL production. RESULTS: UTI was confirmed using a positive urine culture for a relevant pathogen in 96/284 (33.8%) of the cases. Enterobacteriaceae accounted for 75% (72/96) of etiologies of UTI in children. The most frequent Enterobacteriaceae spp. were E. coli, 44.4% (32/72) and K. pneumonia, 27.8% (20/72). The overall multidrug resistance rate was 86.1% (62/72). ESBL-producers accounted for 41.7% (30/72) of the isolated Enterobacteriaceae. ESBL producing K. pneumonia and E. coli isolates accounted for 70% (14/20) and 37.5% (12/32), respectively. History of UTI in the past 1 year (adjusted odds ratio (AoR) = 0.08, 95%CI (0.01 - 0.57)) and medium family wealth index (AoR = 0.03, 95%CI (0.00 - 0.27)) protected from infection with ESBL-producing Enterobacteriaceae. Conclusion. ESBL production was more common in K. pneumonia and appeared to be a major factor contributing drug resistance UTI in children. The findings call for the need to incorporate ESBL testing in the routine clinical practice. The resistance level to commonly prescribed first-line antibiotics observed within Enterobacteriaceae was alarming calling for strengthened antimicrobial stewardship.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana/métodos , Infecciones Urinarias/microbiología , beta-Lactamasas/biosíntesis , Adolescente , Niño , Preescolar , Pruebas Antimicrobianas de Difusión por Disco/métodos , Farmacorresistencia Bacteriana , Enterobacteriaceae/patogenicidad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/patologíaRESUMEN
In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.
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Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Bacteriemia/tratamiento farmacológico , Ceftazidima/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Terapia Recuperativa/métodos , Adulto , Bacteriemia/microbiología , Bacteriemia/mortalidad , Bacteriemia/patología , Carbapenémicos/uso terapéutico , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/enzimología , Enterobacteriaceae/crecimiento & desarrollo , Enterobacteriaceae/patogenicidad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/mortalidad , Infecciones por Enterobacteriaceae/patología , Femenino , Expresión Génica , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/mortalidad , Neumonía Bacteriana/patología , Polimixinas/uso terapéutico , Estudios Prospectivos , Análisis de Supervivencia , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
There is great interest in safe and effective alternative therapies that could benefit patients with inflammatory bowel diseases (IBD). L-arginine (Arg) is a semi-essential amino acid with a variety of physiological effects. In this context, our aim was to investigate the role of dietary Arg in experimental colitis. We used two models of colitis in C57BL/6 mice, the dextran sulfate sodium (DSS) model of injury and repair, and Citrobacter rodentium infection. Animals were given diets containing (1) no Arg (Arg0), 6.4 g/kg (ArgNL), or 24.6 g/kg Arg (ArgHIGH); or (2) the amino acids downstream of Arg: 28 g/kg L-ornithine (OrnHIGH) or 72 g/kg L-proline (ProHIGH). Mice with DSS colitis receiving the ArgHIGH diet had increased levels of Arg, Orn, and Pro in the colon and improved body weight loss, colon length shortening, and histological injury compared to ArgNL and Arg0 diets. Histology was improved in the ArgNL vs. Arg0 group. OrnHIGH or ProHIGH diets did not provide protection. Reduction in colitis with ArgHIGH diet also occurred in C. rodentium-infected mice. Diversity of the intestinal microbiota was significantly enhanced in mice on the ArgHIGH diet compared to the ArgNL or Arg0 diets, with increased abundance of Bacteroidetes and decreased Verrucomicrobia. In conclusion, dietary supplementation of Arg is protective in colitis models. This may occur by restoring overall microbial diversity and Bacteroidetes prevalence. Our data provide a rationale for Arg as an adjunctive therapy in IBD.
Asunto(s)
Arginina/administración & dosificación , Colitis/patología , Colon/microbiología , Dieta/métodos , Infecciones por Enterobacteriaceae/patología , Microbioma Gastrointestinal , Animales , Citrobacter rodentium/crecimiento & desarrollo , Colitis/inducido químicamente , Colon/patología , Sulfato de Dextran/administración & dosificación , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Histocitoquímica , Ratones Endogámicos C57BL , Resultado del TratamientoRESUMEN
INTRODUCTION: Live maggot infestation (myiasis) of wounds can present a host of ailments. Loosely associated with maggot excreta, Morganella morganii is a widespread, gram-negative rod bacterium commonly found in the intestinal tracts of humans. M morganii has been observed as being pathogenic, particularly in nosocomial and postoperative environments, as well as in immunosuppressed and elderly populations. CASE REPORT: Herein, the authors present a rare, previously unreported case of M morganii septicemia (as confirmed by positive blood culture), secondary to myiasis of the lower extremities. The patient was successfully treated with both systemic and topical interventions. Posttreatment examination revealed resolution of myiasis and negative blood cultures. CONCLUSIONS: Myiasis can be invasive, leading to severe systemic infection. In these cases, a broad-spectrum antibiotic combined with systemic and topical antiparasitic therapy should be considered.
Asunto(s)
Infecciones por Enterobacteriaceae/patología , Hiperqueratosis Epidermolítica/patología , Extremidad Inferior/patología , Morganella morganii/patogenicidad , Miasis/complicaciones , Síndrome Postrombótico/complicaciones , Sepsis/patología , Administración Intravenosa , Administración Tópica , Anciano de 80 o más Años , Carbapenémicos/administración & dosificación , Infecciones por Enterobacteriaceae/terapia , Humanos , Hidroterapia/métodos , Hiperqueratosis Epidermolítica/parasitología , Hiperqueratosis Epidermolítica/terapia , Insecticidas/administración & dosificación , Extremidad Inferior/parasitología , Masculino , Miasis/patología , Miasis/terapia , Pomadas/administración & dosificación , Permetrina/administración & dosificación , Síndrome Postrombótico/fisiopatología , Síndrome Postrombótico/terapia , Sepsis/parasitología , Sepsis/terapia , Resultado del TratamientoRESUMEN
Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic Escherichia coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer. In particular, through in silico analysis of the distribution of the CNF1-like deamidase active site Gly-Cys-(Xaa)n-His sequence motif in bacterial genomes, we unveil the wide distribution of the super-family of CNF-like toxins and CNF-like deamidase domains among members of the Enterobacteriacae and in association with a large variety of toxin delivery systems. We extent our discussion with recent findings concerning cellular systems that control activated Rac1 GTPase stability and provide protection against cancer. These findings point to the urgency for developing holistic approaches toward personalized medicine that include monitoring for asymptomatic carriage of pathogenic toxin-producing bacteria and that ultimately might lead to improved public health and increased lifespans.
Asunto(s)
Amidohidrolasas/metabolismo , Toxinas Bacterianas/metabolismo , Enterobacteriaceae/enzimología , Proteínas de Escherichia coli/metabolismo , Factores Inmunológicos/metabolismo , Factores de Virulencia/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Amidohidrolasas/genética , Asparagina/metabolismo , Toxinas Bacterianas/genética , Biología Computacional , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/patología , Proteínas de Escherichia coli/genética , Glutamina/metabolismo , Neoplasias/etiología , Neoplasias/fisiopatología , Factores de Virulencia/genéticaRESUMEN
Many enteric pathogens, including Salmonella and enteropathogenic and enterohemorrhagic Escherichia coli, express adhesins that recognize and bind to carbohydrate moieties expressed on epithelial cells. An attractive strategy for inhibiting bacterial adherence employs molecules that mimic these epithelial binding sites. Prebiotic oligosaccharides are non-digestible, fermentable fibres capable of modulating the gut microbiota. Moreover, they may act as molecular decoys that competitively inhibit adherence of pathogens to host cells. In particular, galactooligosaccharides (GOS) and other prebiotic fibres have been shown to inhibit pathogen adherence to epithelial cells in vitro. In the present study, we determined the ability of prophylactic GOS administration to reduce enteric pathogen adherence both in vitro and in vivo as well as protect against intestinal inflammation. GOS supplementation significantly reduced the adherence of the epithelial-adherent murine bacterial pathogen Citrobacter rodentium in a dose-dependent manner to the surface of epithelial cells in vitro. A 1- to 2-log reduction in bacterial adherence was observed at the lowest and highest doses tested, respectively. However, mouse studies revealed that treatment with GOS neither reduced the adherence of C. rodentium to the distal colon nor decreased its dissemination to systemic organs. Despite the absence of adherence inhibition, colonic disease scores for GOS-treated, C. rodentium-infected mice were significantly lower than those of untreated C. rodentium-infected animals (P=0.028). Together, these data suggest that GOS has a direct protective effect in ameliorating disease severity following C. rodentium infection through an anti-adherence-independent mechanism.
Asunto(s)
Citrobacter rodentium/efectos de los fármacos , Colitis/prevención & control , Suplementos Dietéticos , Infecciones por Enterobacteriaceae/prevención & control , Galactanos/farmacología , Prebióticos/administración & dosificación , Animales , Adhesión Bacteriana/efectos de los fármacos , Línea Celular Tumoral , Colitis/microbiología , Colitis/patología , Colon/microbiología , Colon/patología , Resistencia a la Enfermedad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Células Epiteliales/microbiología , Heces/microbiología , Femenino , Galactanos/administración & dosificación , Humanos , Ratones Endogámicos C57BL , VirulenciaRESUMEN
The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal ß-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other ß-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being less active than only meropenem (95.6% susceptible) among the ß-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-ß-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly blaCTX-M-15-like (89 isolates) and blaCTX-M-14-like (22) genes but also blaSHV (31) and blaTEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All ß-lactams displayed limited activity against blaKPC-carrying isolates. Ceftolozane-tazobactam was the most active ß-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae, including isolates resistant to cephalosporins and carrying ESBL genes.
Asunto(s)
Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Tazobactam/uso terapéutico , Cefepima/uso terapéutico , Ceftazidima/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/enzimología , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Expresión Génica , Hospitalización , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Meropenem/uso terapéutico , Pruebas de Sensibilidad Microbiana , Combinación Piperacilina y Tazobactam/uso terapéutico , Plásmidos/química , Plásmidos/metabolismo , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/patología , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/patología , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/microbiología , Sistema Respiratorio/patología , Estudios Retrospectivos , Estados Unidos/epidemiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
INTRODUCTION: Tigecycline, a derivative of minocycline, is an extended-spectrum antimicrobial agent. It has a restricted approval field in children and the experience of its adoption in clinical practice is reserved for cases of challenging infections. The aim of this review was to summarize evidence regarding the use of tigecycline in infants and children, focusing on the drug's clinical efficacy data and tolerability profile. Areas covered: We have conducted a literature search of the Cochrane Library, EMBASE, and MEDLINE databases, from their inception through 5 January 2017, using the following terms: tigecycline, newborn, infant, child, pediatrics, adolescent, human, clinical trial, and case report. Articles were excluded if they were redundant or not pertinent. Bibliographies of all relevant articles were also evaluated. Seventeen publications were included: 1 pharmacokinetic study, 16 case reports. In the selected publications, the patients' mean age was 4.45 years, 38.7% of children was <3 years old and favorable clinical response was achieved in 74.2% of cases. Expert commentary: Tigecycline may be a considerable option in life-threatening infections in pediatric patients. Its administration is well tolerated and has demonstrated a good clinical response in nonbacteremic patients. However, the available clinical records are limited and more studies are needed.
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Infecciones por Acinetobacter/tratamiento farmacológico , Antibacterianos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Minociclina/análogos & derivados , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/patología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/crecimiento & desarrollo , Acinetobacter baumannii/patogenicidad , Adolescente , Niño , Preescolar , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/crecimiento & desarrollo , Enterobacteriaceae/patogenicidad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Humanos , Lactante , Recién Nacido , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Pruebas de Sensibilidad Microbiana , Minociclina/uso terapéutico , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Tigeciclina , Resultado del TratamientoRESUMEN
Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity ). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).
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Antibacterianos/uso terapéutico , Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Peritonitis/tratamiento farmacológico , Cavidad Abdominal/microbiología , Cavidad Abdominal/patología , Candida/crecimiento & desarrollo , Candida/patogenicidad , Candidiasis/microbiología , Candidiasis/patología , Carbapenémicos/uso terapéutico , Enfermedad Crítica , Farmacorresistencia Bacteriana Múltiple , Enterobacteriaceae/crecimiento & desarrollo , Enterobacteriaceae/patogenicidad , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Fluoroquinolonas/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Minociclina/análogos & derivados , Minociclina/uso terapéutico , Peritonitis/microbiología , Peritonitis/patología , Guías de Práctica Clínica como Asunto , Factores de Riesgo , TigeciclinaRESUMEN
Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.
Asunto(s)
Caenorhabditis elegans/efectos de los fármacos , Infecciones por Enterobacteriaceae/patología , Mucosa Intestinal/patología , Intestinos/patología , Hierro de la Dieta/administración & dosificación , Salmonelosis Animal/metabolismo , Proteínas de Fase Aguda/biosíntesis , Proteínas de Fase Aguda/inmunología , Animales , Peso Corporal/inmunología , Caenorhabditis elegans/inmunología , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiología , Citrobacter rodentium/inmunología , Dieta/métodos , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Heces/microbiología , Femenino , Inmunidad Innata , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Intestinos/inmunología , Intestinos/microbiología , Hierro de la Dieta/efectos adversos , Complejo de Antígeno L1 de Leucocito/biosíntesis , Complejo de Antígeno L1 de Leucocito/inmunología , Lipocalina 2 , Lipocalinas/biosíntesis , Lipocalinas/inmunología , Ratones , Ratones Endogámicos C57BL , Proteínas Oncogénicas/biosíntesis , Proteínas Oncogénicas/inmunología , Salmonelosis Animal/inmunología , Salmonelosis Animal/microbiología , Salmonelosis Animal/mortalidad , Salmonella typhimurium/inmunología , Análisis de SupervivenciaAsunto(s)
Cefoxitina/uso terapéutico , Cefalosporinas/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Resistencia betalactámica , Estructuras Animales/microbiología , Animales , Carga Bacteriana , Cefepima , Cefoxitina/farmacología , Cefalosporinas/farmacología , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Quimioterapia Combinada , Enterobacteriaceae/enzimología , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Análisis de Supervivencia , Resultado del Tratamiento , beta-Lactamasas/metabolismoRESUMEN
Inflammatory bowel disease is an intestinal inflammatory disorder of multifactorial origin, in which diets that favor high n-6 and low n-3 fatty acids have been implicated. The present study addressed whether dietary n-6 and n-3 fatty acids alter colonic mucosal response to Citrobacter rodentium (C. rodentium) infection. Mice were fed diets identical except for fatty acids, with an energy percentage of 15% 18:2n-6 and <0.06% 18:3n-3, 4.2% 18:2n-6 and 1.9% 18:3n-3, or 1.44% 20:5n-3, 4.9% 22:6n-3, 0.32% 18:2n-6, and 0.12% 18:3n-3 from safflower, canola, or fish oil, respectively for 3 wk before infection. Dietary oils had no effect on colonic C. rodentium growth but altered colon 20:4n-6/(20:5n-3+22:6n-3) with 9.40 ± 0.06, 1.94 ± 0.08, and 0.32 ± 0.03% in colon phosphatidylcholine and 3.82 ± 0.18, 1.14 ± 0.02, and 0.30 ± 0.02% in phosphatidylethanolamine of mice fed safflower, canola, or fish oil, respectively. At 10 days postinfection, histological damage, F4/80-positive macrophages, and myeloperoxidase-positive neutrophils in colonic mucosa were higher in infected mice fed safflower than fish oil. Colon gene transcripts for macrophage inflammatory protein 2, keratinocyte cytokine, and monocyte chemoattractant protein 1 expression were significantly higher in infected mice fed safflower than canola or fish oil; IFN-γ, IL-6, and IL-17A expression were significantly elevated in mice fed safflower rather than fish oil; and IL-10 was significantly higher in mice fed fish oil rather than canola or safflower oil. This study demonstrates that oils high in 18:2n-6 with minimal n-3 fatty acids exacerbate mucosal immune response, whereas oils high in n-3 fatty acids attenuate mucosal immune response to C. rodentium. These studies implicate dietary oils as environmental modifiers of intestinal inflammation in response to infection.
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Citrobacter rodentium , Colon/patología , Grasas Insaturadas en la Dieta/farmacología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/patología , Inmunidad/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Carga Bacteriana , Proliferación Celular/efectos de los fármacos , Colitis/patología , Colon/metabolismo , Citocinas/análisis , Citocinas/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Heces/microbiología , Fluoresceína-5-Isotiocianato , Técnica del Anticuerpo Fluorescente , Inflamación/patología , Ratones , Ratones Endogámicos C57BL , Permeabilidad , Fosfolípidos/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaAsunto(s)
Antibacterianos/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Levofloxacino/uso terapéutico , Prostatitis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Enfermedad Crónica , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/crecimiento & desarrollo , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/patología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Próstata/efectos de los fármacos , Próstata/microbiología , Próstata/patología , Prostatitis/microbiología , Prostatitis/patología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Staphylococcus/efectos de los fármacos , Staphylococcus/crecimiento & desarrollo , Resultado del TratamientoRESUMEN
Citrobacter rodentium is a mouse pathogen that causes infectious colitis and shares characteristics with human enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli, including the ability to cause attaching and effacing lesions in the colon and serves as a useful model to study the pathogenicity of these bacteria. In this study, mice were fed a selenium-deficient diet for 5 or 20 weeks and then infected with C. rodentium. Colonization of the colon by C. rodentium was similar in mice fed adequate or selenium-deficient diets, but total bacterial colonization of the spleen was elevated in mice fed selenium-deficient diet for 20 weeks. Infection-induced changes to the colon included inflammatory cell infiltration, gross changes in crypt architecture, and ulceration and denuding of the epithelial layer that were greatest in mice fed a selenium-deficient diet for 20 weeks. Expression of pro-inflammatory genes was significantly higher 12-days post-infection in mice fed the selenium-deficient diet for 20 weeks compared to mice fed a selenium-adequate diet or selenium-deficient diet for 5 weeks. Diarrhea was prevalent in mice fed the selenium-deficient diet for 20 weeks but not 5 weeks, and this was associated with decreased expression of solute carrier family 26a3 and carbonic anhydrase IV, genes involved in ion transport. These results indicated that selenium played an important role in resistance to the pathological effects of a C. rodentium infection, and therefore, selenium status may be important in the expression of human disease caused by common food-borne bacteria.
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Citrobacter rodentium/patogenicidad , Infecciones por Enterobacteriaceae/microbiología , Selenio/deficiencia , Animales , Antígenos Bacterianos/inmunología , Traslocación Bacteriana , Peso Corporal/fisiología , Colon/metabolismo , Colon/patología , ADN Complementario/biosíntesis , ADN Complementario/genética , Dieta , Resistencia a la Enfermedad/fisiología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/patología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/fisiología , Expresión Génica/fisiología , Glutatión Peroxidasa/metabolismo , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/fisiología , ARN/biosíntesis , ARN/genética , Bazo/fisiologíaRESUMEN
The pathogenesis of a Citrobacter rodentium infection was evaluated in mice fed diets with a single deficiency in either selenium or vitamin E or with a double deficiency in both selenium and vitamin E compared to mice on nutritionally adequate diets. Mice fed the selenium- and vitamin E-deficient diet for 6 weeks had increased loads of C. rodentium in the colon and spleen, which were not observed in mice fed either of the singly deficient diets or the adequate diet. Infected mice fed the doubly deficient diet had increased colon crypt hyperplasia and an influx of infiltrating cells along with gross changes to crypt architecture, including ulceration and denuding of the epithelial layer. Cytokine and chemokine mRNA levels in the colon were measured by real-time PCR. Expression of proinflammatory cytokines and chemokines was upregulated on day 12 after infection with C. rodentium in mice fed the doubly deficient diet compared to mice fed the control diet. Heme oxygenase 1, an enzyme upregulated by oxidative stress, also was more highly induced in infected mice fed the doubly deficient diet. Production of C. rodentium antigen-specific IgM and IgG antibodies was not affected by feeding the doubly deficient diet. The results indicated that selenium and vitamin E play an important role in host resistance and in the pathology induced by C. rodentium, an infection that mimics disease caused by common food-borne bacterial pathogens in humans.
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Antioxidantes/metabolismo , Citrobacter rodentium/patogenicidad , Infecciones por Enterobacteriaceae/metabolismo , Selenio/deficiencia , Deficiencia de Vitamina E/microbiología , Animales , Citrobacter rodentium/inmunología , Citrobacter rodentium/metabolismo , Colon/inmunología , Colon/microbiología , Colon/patología , Citocinas/biosíntesis , Dieta , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Enterobacteriaceae/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Selenio/inmunología , Deficiencia de Vitamina E/inmunología , Deficiencia de Vitamina E/metabolismoRESUMEN
Edwardsiella tarda is a severe aquaculture pathogen that can infect many different fish species cultured worldwide. Et49 is a major E. tarda antigen with weak immunoprotective potential. In this study, using Et49 as an example vaccine, the adjuvanticity of Freund's incomplete adjuvant (FIA), aluminum hydroxide, and aluminum phosphate adjuvant were evaluated in a Japanese flounder model. The results showed that the presence of FIA, aluminum hydroxide, and aluminum phosphate adjuvant increased the relative percent of survival of Et49-vaccinated fish by 47%, 19%, and 35%, respectively. Fish vaccinated with FIA-adjuvanted Et49 exhibited longer persistence of vaccine at the injection site and more severe intra-abdominal lesions than fish vaccinated with aluminum-adjuvanted Et49. Both aluminum adjuvants and, to a lesser degree, FIA augmented the production of specific serum antibodies, which reached the highest levels at 6 and 7 weeks post-vaccination. Passive immunization of Japanese flounder with sera from fish vaccinated with aluminum- and FIA-adjuvanted Et49 induced no protection against lethal E. tarda challenge. Examination of the transcription profile of immune-related genes showed that vaccination with aluminum-adjuvanted Et49 significantly enhanced the expression of the genes that are associated mainly with humoral immunity, whereas vaccination with FIA-adjuvanted Et49 induced the expression of a much broader spectrum of genes that are likely to be involved in humoral and innate cellular immunity. These results provide new insights to the action mechanisms of FIA and aluminum adjuvants in Japanese flounder and may be useful for the selection of adjuvant for vaccine formulations intended for Japanese flounder.