Dataset Information

Management of Clostridioides difficile colitis: insights for the gastroenterologist.

ABSTRACT: Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.

SUBMITTER: Saha S

PROVIDER: S-EPMC6505238 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Management of <i>Clostridioides difficile</i> colitis: insights for the gastroenterologist.

Saha Srishti S Khanna Sahil S

Therapeutic advances in gastroenterology 20190506

<i>Clostridioides difficile</i> infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of lit ...[more]

PMID: 31105766

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Project description:The response to iron limitation of several bacteria is regulated by the ferric uptake regulator (Fur). The Fur-regulated transcriptional, translational and metabolic networks of the Gram-positive, pathogen Clostridioides difficile were investigated by a combined RNA sequencing, proteomic, metabolomic and electron microscopy approach. At high iron conditions (760 g/l) the C. difficile fur mutant displayed a growth deficiency compared to wild type C. difficile cells. Several iron transporters were found induced by Fur regulation during low iron (11 g/l) conditions. The major adaptation to low iron conditions was observed for the central energy metabolism. Most ferredoxin-dependent amino acid fermentations were found significantly down regulated (had, etf, acd, grd, trx, bdc, hbd). The substrates of these pathways phenylalanine, leucine, glycine and some initial intermediates (phenylpyruvate, oxo-isocaproate, 3-hydroxy-butanoyl-CoA, crotonyl-CoA) were found accumulated, while some end product like isocaproate and butanoate were found reduced. Flavodoxin (fldX) formation and riboflavin biosynthesis (rib) were found enhanced, most likely to replace the missing ferredoxins. Proline reductase (prd), the corresponding ion pumping RNF complex (rnf) and the reaction product 5-aminovalerate were significantly enhanced. An ATP forming ATPase (atpCDGAHFEB,) of the F0F1-type was found induced while the formation of a V-type, mostly proton-pumping, ATP-consuming ATPase (atpDBAFCEKI, was decreased. The [Fe-S] enzyme-dependent pyruvate formate lyase (pfl), formate dehydrogenase (fdh) and hydrogenase (hyd) branch of glucose utilization and glycogen biosynthesis (glg) were significantly reduced, leading to an accumulation of glucose and pyruvate. The formation of [Fe-S] enzyme carbon monoxide dehydrogenase (coo) was inhibited. An intensive remodeling of the cell wall was observed most likely to increase antibiotic resistance. Polyamine biosynthesis (spe) was found induced leading to an accumulation of spermine, spermidine and putrescine. The fur mutant lost most of its flagella. Finally, the CRISPR/Cas and a prophage encoding operon were downregulated. Fur binding sites were found upstream of 20 of the regulated genes. Overall, adaptation to low iron conditions in C. difficile focused on an increase of iron import, significant decrease in metabolic iron utilization and protection during the complex transition.

Dataset Information

Management of Clostridioides difficile colitis: insights for the gastroenterologist.

Publications

Management of <i>Clostridioides difficile</i> colitis: insights for the gastroenterologist.

Similar Datasets

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