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Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications.
J Antimicrob Chemother. 2013 Jun; 68(6):1305-11.JA

Abstract

OBJECTIVES

In November 2008, a study was performed with support from the European Centre for Disease Prevention and Control (ECDC) to obtain an overview of Clostridium difficile infections (CDIs) in European hospitals. A collection of 398 C. difficile isolates obtained from this hospital-based survey was utilized to identify antimicrobial susceptibility patterns of common C. difficile PCR ribotypes across Europe.

METHODS

The MICs of three approved therapeutic agents (vancomycin, metronidazole and fidaxomicin) and LFF571 (a novel semi-synthetic thiopeptide antibiotic) were determined by the agar dilution method.

RESULTS

MICs of fidaxomicin and LFF571 were in general 2-4-fold lower than those of vancomycin and metronidazole. Isolates belonging to clade 2, including the hypervirulent ribotype 027, had one-dilution higher MIC50 and MIC90 values for fidaxomicin and metronidazole, whereas similar MIC values were observed for vancomycin and LFF571. Isolates belonging to C. difficile PCR ribotype 001 were more susceptible to fidaxomicin than other frequently found PCR ribotypes 014/020 and 078. Six isolates from three different countries had a metronidazole MIC of 2 mg/L. Four of the six isolates were characterized as PCR ribotype 001.

CONCLUSIONS

There was no evidence of in vitro resistance of C. difficile to any of the four agents tested. However, the results suggest type-specific differences in susceptibility for the treatment agents we investigated. Continuous surveillance of C. difficile isolates in Europe is needed to determine the possible clinical implications of ribotype-specific changes in susceptibility to therapeutic agents.

Authors+Show Affiliations

Centre for Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23420839

Citation

Debast, Sylvia B., et al. "Antimicrobial Activity of LFF571 and Three Treatment Agents Against Clostridium Difficile Isolates Collected for a pan-European Survey in 2008: Clinical and Therapeutic Implications." The Journal of Antimicrobial Chemotherapy, vol. 68, no. 6, 2013, pp. 1305-11.
Debast SB, Bauer MP, Sanders IM, et al. Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications. J Antimicrob Chemother. 2013;68(6):1305-11.
Debast, S. B., Bauer, M. P., Sanders, I. M., Wilcox, M. H., & Kuijper, E. J. (2013). Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications. The Journal of Antimicrobial Chemotherapy, 68(6), 1305-11. https://doi.org/10.1093/jac/dkt013
Debast SB, et al. Antimicrobial Activity of LFF571 and Three Treatment Agents Against Clostridium Difficile Isolates Collected for a pan-European Survey in 2008: Clinical and Therapeutic Implications. J Antimicrob Chemother. 2013;68(6):1305-11. PubMed PMID: 23420839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications. AU - Debast,Sylvia B, AU - Bauer,Martijn P, AU - Sanders,Ingrid M J G, AU - Wilcox,Mark H, AU - Kuijper,Ed J, AU - ,, Y1 - 2013/02/18/ PY - 2013/2/20/entrez PY - 2013/2/20/pubmed PY - 2013/12/16/medline KW - MICs KW - fidaxomicin KW - metronidazole KW - vancomycin SP - 1305 EP - 11 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 68 IS - 6 N2 - OBJECTIVES: In November 2008, a study was performed with support from the European Centre for Disease Prevention and Control (ECDC) to obtain an overview of Clostridium difficile infections (CDIs) in European hospitals. A collection of 398 C. difficile isolates obtained from this hospital-based survey was utilized to identify antimicrobial susceptibility patterns of common C. difficile PCR ribotypes across Europe. METHODS: The MICs of three approved therapeutic agents (vancomycin, metronidazole and fidaxomicin) and LFF571 (a novel semi-synthetic thiopeptide antibiotic) were determined by the agar dilution method. RESULTS: MICs of fidaxomicin and LFF571 were in general 2-4-fold lower than those of vancomycin and metronidazole. Isolates belonging to clade 2, including the hypervirulent ribotype 027, had one-dilution higher MIC50 and MIC90 values for fidaxomicin and metronidazole, whereas similar MIC values were observed for vancomycin and LFF571. Isolates belonging to C. difficile PCR ribotype 001 were more susceptible to fidaxomicin than other frequently found PCR ribotypes 014/020 and 078. Six isolates from three different countries had a metronidazole MIC of 2 mg/L. Four of the six isolates were characterized as PCR ribotype 001. CONCLUSIONS: There was no evidence of in vitro resistance of C. difficile to any of the four agents tested. However, the results suggest type-specific differences in susceptibility for the treatment agents we investigated. Continuous surveillance of C. difficile isolates in Europe is needed to determine the possible clinical implications of ribotype-specific changes in susceptibility to therapeutic agents. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/23420839/Antimicrobial_activity_of_LFF571_and_three_treatment_agents_against_Clostridium_difficile_isolates_collected_for_a_pan_European_survey_in_2008:_clinical_and_therapeutic_implications_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkt013 DB - PRIME DP - Unbound Medicine ER -