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...

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Autores principales:	Alexis Fong, Megan Ross, Justin Boudreau, Reza Nokhbeh, Kim Tilbe, Hoyun Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81d1e77f48bb42818e9e32cdc31980c4
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spelling	oai:doaj.org-article:81d1e77f48bb42818e9e32cdc31980c42021-12-02T20:14:48ZRaja 42, a novel gamma lactam compound, is effective against Clostridioides difficile.1932-620310.1371/journal.pone.0257143https://doaj.org/article/81d1e77f48bb42818e9e32cdc31980c42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257143https://doaj.org/toc/1932-6203Clostridioides 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.Alexis FongMegan RossJustin BoudreauReza NokhbehKim TilbeHoyun LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257143 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexis Fong Megan Ross Justin Boudreau Reza Nokhbeh Kim Tilbe Hoyun Lee Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile.
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	article
author	Alexis Fong Megan Ross Justin Boudreau Reza Nokhbeh Kim Tilbe Hoyun Lee
author_facet	Alexis Fong Megan Ross Justin Boudreau Reza Nokhbeh Kim Tilbe Hoyun Lee
author_sort	Alexis Fong
title	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_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_sort	raja 42, a novel gamma lactam compound, is effective against clostridioides difficile.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/81d1e77f48bb42818e9e32cdc31980c4
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Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile.

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