Abstract
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.
Highlights
Clostridioides difficile, a Gram-positive bacillus bacterium, is the primary cause of hospitalacquired diarrhea that often happens to patients with prior exposure to antimicrobial agents
We have found that Raja 42 is effective against both Gram-positive and Gram-negative bacteria, including Escherichia coli, methicillin-resistant S. aureus (MRSA), and Helicobacter pylori
The susceptibility profiles determined by minimum inhibitory concentration (MIC) showed unimodal distribution for both metronidazole (Fig 1C) and vancomycin (Fig 1E), which are largely consistent with published C. difficile data by EUCAST (2019)
Summary
Clostridioides difficile, a Gram-positive bacillus bacterium, is the primary cause of hospitalacquired diarrhea that often happens to patients with prior exposure to antimicrobial agents. It has been estimated that C. difficile infection (CDI) is responsible for over 500,000 enteric infections a year in the United States alone [1]. CDI causes colitis, which can lead to death if left untreated [2]. Raja 42, a γ-lactam, is effective against C. difficile serious problem [3,4]. The development of safe and powerful new drugs is highly desirable; the number of potentially effective novel antimicrobial agents in the pipeline is declining in recent years, raising serious concerns
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
