Cargando…

Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile

Clostridioides difficile infection (CDI) is the primary cause of hospital-acquired diarrhea, and responsible for over 500,000 enteric infections a year in the United States alone. Although most patients with CDI are successfully treated with metronidazole or vancomycin, the high rate of recurrence i...

Descripción completa

Detalles Bibliográficos
Autores principales: Fong, Alexis, Ross, Megan, Boudreau, Justin, Nokhbeh, Reza, Tilbe, Kim, Lee, Hoyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423298/
https://www.ncbi.nlm.nih.gov/pubmed/34492076
http://dx.doi.org/10.1371/journal.pone.0257143
_version_ 1783749438586486784
author Fong, Alexis
Ross, Megan
Boudreau, Justin
Nokhbeh, Reza
Tilbe, Kim
Lee, Hoyun
author_facet Fong, Alexis
Ross, Megan
Boudreau, Justin
Nokhbeh, Reza
Tilbe, Kim
Lee, Hoyun
author_sort Fong, Alexis
collection PubMed
description Clostridioides difficile infection (CDI) is the primary cause of hospital-acquired diarrhea, and responsible for over 500,000 enteric infections a year in the United States alone. Although most patients with CDI are successfully treated with metronidazole or vancomycin, the high rate of recurrence is still a serious problem, in which case these antibiotics are usually not very effective. The primary objective of this research is to develop a potentially effective therapeutic agent against C. difficile that are resistant to metronidazole or vancomycin. The susceptibility to metronidazole and vancomycin was examined with 194 C. difficile clinical isolates. Sixty of these isolates chosen based on a variety of criteria were examined for their susceptibility against the 4-chloro-1-piperidin-1ylmethyl-1H-indole-2,3-dione compound (Raja 42), a novel isatin–benzothiazole analogue containing a gamma-lactam structure, as we previously found that this novel compound is effective against a variety of different bacteria. Most of the 60 isolates were resistant to ceftriaxone and ciprofloxacin, raising the possibility that they might have been exposed previously to these or structurally similar antibiotics (e.g., β-lactam and quinolone compounds). Among the isolates, 48 (80%) and 54 (90%) were susceptible to metronidazole and vancomycin, respectively. Raja 42 was found to be effective against most of the isolates, especially so against metronidazole-resistant C. difficile. Most importantly, five isolates that show resistance to metronidazole and vancomycin were sensitive to Raja 42. Thus, Raja 42, a gamma lactam antibiotic, has the potential to effectively control C. difficile strains that are resistant to metronidazole and vancomycin.
format Online
Article
Text
id pubmed-8423298
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-84232982021-09-08 Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile Fong, Alexis Ross, Megan Boudreau, Justin Nokhbeh, Reza Tilbe, Kim Lee, Hoyun PLoS One Research Article Clostridioides difficile infection (CDI) is the primary cause of hospital-acquired diarrhea, and responsible for over 500,000 enteric infections a year in the United States alone. Although most patients with CDI are successfully treated with metronidazole or vancomycin, the high rate of recurrence is still a serious problem, in which case these antibiotics are usually not very effective. The primary objective of this research is to develop a potentially effective therapeutic agent against C. difficile that are resistant to metronidazole or vancomycin. The susceptibility to metronidazole and vancomycin was examined with 194 C. difficile clinical isolates. Sixty of these isolates chosen based on a variety of criteria were examined for their susceptibility against the 4-chloro-1-piperidin-1ylmethyl-1H-indole-2,3-dione compound (Raja 42), a novel isatin–benzothiazole analogue containing a gamma-lactam structure, as we previously found that this novel compound is effective against a variety of different bacteria. Most of the 60 isolates were resistant to ceftriaxone and ciprofloxacin, raising the possibility that they might have been exposed previously to these or structurally similar antibiotics (e.g., β-lactam and quinolone compounds). Among the isolates, 48 (80%) and 54 (90%) were susceptible to metronidazole and vancomycin, respectively. Raja 42 was found to be effective against most of the isolates, especially so against metronidazole-resistant C. difficile. Most importantly, five isolates that show resistance to metronidazole and vancomycin were sensitive to Raja 42. Thus, Raja 42, a gamma lactam antibiotic, has the potential to effectively control C. difficile strains that are resistant to metronidazole and vancomycin. Public Library of Science 2021-09-07 /pmc/articles/PMC8423298/ /pubmed/34492076 http://dx.doi.org/10.1371/journal.pone.0257143 Text en © 2021 Fong et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fong, Alexis
Ross, Megan
Boudreau, Justin
Nokhbeh, Reza
Tilbe, Kim
Lee, Hoyun
Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title_full Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title_fullStr Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title_full_unstemmed Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title_short Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile
title_sort raja 42, a novel gamma lactam compound, is effective against clostridioides difficile
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423298/
https://www.ncbi.nlm.nih.gov/pubmed/34492076
http://dx.doi.org/10.1371/journal.pone.0257143
work_keys_str_mv AT fongalexis raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile
AT rossmegan raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile
AT boudreaujustin raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile
AT nokhbehreza raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile
AT tilbekim raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile
AT leehoyun raja42anovelgammalactamcompoundiseffectiveagainstclostridioidesdifficile