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Emergence of reduced susceptibility to metronidazole in Clostridium difficile.
J Antimicrob Chemother. 2008 Nov; 62(5):1046-52.JA

Abstract

OBJECTIVES

Antimicrobial treatment for Clostridium difficile infection (CDI) has typically been metronidazole, although reports have questioned the efficacy of this option. We screened recently isolated C. difficile (2005-06) for susceptibility to metronidazole and compared results for historic isolates (1995-2001).

METHODS

C. difficile ribotypes 001 (n = 86), 106 (n = 81) and 027 (n = 48) and isolates from the 10 other most prevalent ribotypes in Leeds (n = 57) were screened using spiral gradient endpoint analysis (SGE). C. difficile with metronidazole SGE MICs > or = 6 mg/L were analysed further by agar incorporation and Etest. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing was performed for 28 C. difficile isolates.

RESULTS

No reduced metronidazole susceptibility was observed in C. difficile ribotypes 106 and 027 (geometric mean SGE MICs 1.11 and 0.90 mg/L, respectively). In contrast, 21 (24.4%) C. difficile ribotype 001 demonstrated reduced susceptibility to metronidazole (geometric mean SGE MICs 3.51 mg/L, P < 0.001). Variations in susceptibility were observed relating to the method and media, but increased metronidazole MICs were confirmed by an agar incorporation method. Geometric mean agar incorporation MICs for historic C. difficile ribotype 001 (n = 72) were 1.03 (range 0.25-2) mg/L compared with 5.94 (4-8) mg/L (P < 0.001) for recent isolates displaying reduced metronidazole susceptibility. MLVA typing revealed two clonal complexes of C. difficile with reduced susceptibility to metronidazole.

CONCLUSIONS

We have demonstrated the emergence of reduced susceptibility to metronidazole in 24.4% of the recent C. difficile ribotype 001 isolates from our institution. Our observations could have implications in the clinical setting due to the poor penetration of metronidazole into the colon.

Authors+Show Affiliations

Department of Microbiology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18693234

Citation

Baines, Simon D., et al. "Emergence of Reduced Susceptibility to Metronidazole in Clostridium Difficile." The Journal of Antimicrobial Chemotherapy, vol. 62, no. 5, 2008, pp. 1046-52.
Baines SD, O'Connor R, Freeman J, et al. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. J Antimicrob Chemother. 2008;62(5):1046-52.
Baines, S. D., O'Connor, R., Freeman, J., Fawley, W. N., Harmanus, C., Mastrantonio, P., Kuijper, E. J., & Wilcox, M. H. (2008). Emergence of reduced susceptibility to metronidazole in Clostridium difficile. The Journal of Antimicrobial Chemotherapy, 62(5), 1046-52. https://doi.org/10.1093/jac/dkn313
Baines SD, et al. Emergence of Reduced Susceptibility to Metronidazole in Clostridium Difficile. J Antimicrob Chemother. 2008;62(5):1046-52. PubMed PMID: 18693234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emergence of reduced susceptibility to metronidazole in Clostridium difficile. AU - Baines,Simon D, AU - O'Connor,Rachael, AU - Freeman,Jane, AU - Fawley,Warren N, AU - Harmanus,Celine, AU - Mastrantonio,Paola, AU - Kuijper,Ed J, AU - Wilcox,Mark H, Y1 - 2008/08/07/ PY - 2008/8/12/pubmed PY - 2008/12/17/medline PY - 2008/8/12/entrez SP - 1046 EP - 52 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 62 IS - 5 N2 - OBJECTIVES: Antimicrobial treatment for Clostridium difficile infection (CDI) has typically been metronidazole, although reports have questioned the efficacy of this option. We screened recently isolated C. difficile (2005-06) for susceptibility to metronidazole and compared results for historic isolates (1995-2001). METHODS: C. difficile ribotypes 001 (n = 86), 106 (n = 81) and 027 (n = 48) and isolates from the 10 other most prevalent ribotypes in Leeds (n = 57) were screened using spiral gradient endpoint analysis (SGE). C. difficile with metronidazole SGE MICs > or = 6 mg/L were analysed further by agar incorporation and Etest. Multiple-locus variable-number tandem-repeat analysis (MLVA) typing was performed for 28 C. difficile isolates. RESULTS: No reduced metronidazole susceptibility was observed in C. difficile ribotypes 106 and 027 (geometric mean SGE MICs 1.11 and 0.90 mg/L, respectively). In contrast, 21 (24.4%) C. difficile ribotype 001 demonstrated reduced susceptibility to metronidazole (geometric mean SGE MICs 3.51 mg/L, P < 0.001). Variations in susceptibility were observed relating to the method and media, but increased metronidazole MICs were confirmed by an agar incorporation method. Geometric mean agar incorporation MICs for historic C. difficile ribotype 001 (n = 72) were 1.03 (range 0.25-2) mg/L compared with 5.94 (4-8) mg/L (P < 0.001) for recent isolates displaying reduced metronidazole susceptibility. MLVA typing revealed two clonal complexes of C. difficile with reduced susceptibility to metronidazole. CONCLUSIONS: We have demonstrated the emergence of reduced susceptibility to metronidazole in 24.4% of the recent C. difficile ribotype 001 isolates from our institution. Our observations could have implications in the clinical setting due to the poor penetration of metronidazole into the colon. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/18693234/Emergence_of_reduced_susceptibility_to_metronidazole_in_Clostridium_difficile_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkn313 DB - PRIME DP - Unbound Medicine ER -