ArticleJournal of clinical microbiology2021
The Integrity of Heme Is Essential for Reproducible Detection of Metronidazole-Resistant Clostridioides difficile by Agar Dilution Susceptibility Tests.
Article in Journal of clinical microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Ecological and dietary strategies to constrain Clostridioides difficile.Cell host & microbe · 2026Review
- Reversion of heme-dependent metronidazole resistance inMicrobiology spectrum · 2026Article
- Comparative genomic analysis of Clostridioides difficile strains in Mexico: insights into virulence and resistance.Access microbiology · 2026Article
- Newly emerging metronidazole-resistantEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025Article
- Article
- Liberation of host heme bymBio · 2024Article
- Host-defense piscidin peptides as antibiotic adjuvants against Clostridioides difficile.PloS one · 2024Article
- Magnetic Fe-doped TiOHeliyon · 2023Article
- Decoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile.Nature communications · 2023Article
- Reply to Gonzales-Luna et al.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Surveillance of Clostridioides difficile Antimicrobial Resistance in the United States.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Systematic Design of Adenosine Analogs as Inhibitors of aJournal of medicinal chemistry · 2023Article
- Make It LessGenes · 2022Review
- Repurposing epigenetic inhibitors to target theEpigenetics · 2022Article
- Mechanisms and impact of antimicrobial resistance in Clostridioides difficile.Current opinion in microbiology · 2022Review
- Haemin deprivation renders Bacteroides fragilis hypersusceptible to metronidazole and cancels high-level metronidazole resistance.The Journal of antimicrobial chemotherapy · 2022Article
- Host and Clostridioides difficile-Response Modulated by Micronutrients and Glutamine: An Overview.Frontiers in nutrition · 2022Review
- Reduced Susceptibility to Metronidazole Is Associated With Initial Clinical Failure inOpen forum infectious diseases · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Metronidazole resistance in clinical Clostridioides difficile is often described as unstable, since resistant strains reportedly appear susceptible following freezer storage or brief passage. This has presented a conundrum for adopting susceptibility testing to accurately evaluate the connection between metronidazole resistance and decreased clinical efficacy of metronidazole in patients with C. difficile infections (CDIs). We discovered that supplementation of microbiological media with the metalloporphyrin heme is crucial for detection of metronidazole-resistant C. difficile using the agar dilution susceptibility testing method. Known metronidazole-resistant strains appeared susceptible to metronidazole in media lacking heme. Similarly, these resistant strains exhibited increased susceptibility to metronidazole when tested on heme-containing agars that were exposed to room light for more than 1 day, likely due to heme photodecomposition. In parallel experiments, resistance was reproducibly detected when heme-containing agars were either prepared and used on the same day or protected from light and then used on subsequent days. Notably, heme did not influence the susceptibilities of drug-susceptible strains that were of the same ribotype as the resistant strains. These findings firmly show that the consistent detection of metronidazole-resistant C. difficile is dependent upon heme and its protection from light. Studies are warranted to determine the extent to which this heme-associated metronidazole-resistant phenotype affects the clinical efficacy of metronidazole in CDI and the underlying genetic and biochemical mechanisms.
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Registered trials
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