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In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin.
J Antimicrob Chemother. 2008 Oct; 62(4):762-5.JA

Abstract

OBJECTIVES

Clostridium difficile infection is a nosocomial disease of increasing importance. First-line treatment is limited to metronidazole or vancomycin. Oritavancin is a lipoglycopeptide with activity against Gram-positive bacteria, including drug-resistant pathogens. MICs of oritavancin, metronidazole and vancomycin for genotypically distinct C. difficile strains, including epidemic C. difficile PCR ribotypes 001 and 027, were determined by agar incorporation and broth macrodilution methods. In agar incorporation methods, the impact of supplements on oritavancin MICs was tested to address oritavancin binding to surfaces.

METHODS

Thirty-three genotypically distinct C. difficile strains were identified by PCR ribotyping. Wilkins Chalgren agar incorporation plates containing oritavancin, metronidazole and vancomycin were prepared with and without 0.002% polysorbate-80 (P80) and lysed horse blood (2%). Broth macrodilution MICs of oritavancin, metronidazole and vancomycin were determined in Brucella broth. Inoculated agar incorporation plates and broth macrodilution tubes were cultured anaerobically at 37 degrees C for 48 h.

RESULTS

Broth macrodilution MICs were lower than agar incorporation MICs for oritavancin, but not for metronidazole and vancomycin. Oritavancin broth macrodilution MIC(90)s were 2- to 4-fold lower than the corresponding agar incorporation MIC(90)s, while geometric mean MICs were >5-fold lower. Oritavancin broth macrodilution MIC(90)s were approximately 2- and 5-fold lower than those for metronidazole and vancomycin. Metronidazole was the most active antimicrobial agent against C. difficile using agar incorporation methods. Oritavancin agar incorporation MIC(90)s were unaffected by 0.002% P80 and/or 2% lysed horse blood.

CONCLUSIONS

Oritavancin was at least 4-fold more potent than vancomycin against the majority (25/33) of C. difficile strains tested by broth macrodilution. Oritavancin activity may be underestimated by agar incorporation methods, regardless of the use of P80 or lysed horse blood.

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 available

Pub Type(s)

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

Language

eng

PubMed ID

18606787

Citation

O'Connor, Rachael, et al. "In Vitro Susceptibility of Genotypically Distinct and Clonal Clostridium Difficile Strains to Oritavancin." The Journal of Antimicrobial Chemotherapy, vol. 62, no. 4, 2008, pp. 762-5.
O'Connor R, Baines SD, Freeman J, et al. In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin. J Antimicrob Chemother. 2008;62(4):762-5.
O'Connor, R., Baines, S. D., Freeman, J., & Wilcox, M. H. (2008). In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin. The Journal of Antimicrobial Chemotherapy, 62(4), 762-5. https://doi.org/10.1093/jac/dkn276
O'Connor R, et al. In Vitro Susceptibility of Genotypically Distinct and Clonal Clostridium Difficile Strains to Oritavancin. J Antimicrob Chemother. 2008;62(4):762-5. PubMed PMID: 18606787.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro susceptibility of genotypically distinct and clonal Clostridium difficile strains to oritavancin. AU - O'Connor,Rachael, AU - Baines,Simon D, AU - Freeman,Jane, AU - Wilcox,Mark H, Y1 - 2008/07/07/ PY - 2008/7/9/pubmed PY - 2008/11/7/medline PY - 2008/7/9/entrez SP - 762 EP - 5 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 62 IS - 4 N2 - OBJECTIVES: Clostridium difficile infection is a nosocomial disease of increasing importance. First-line treatment is limited to metronidazole or vancomycin. Oritavancin is a lipoglycopeptide with activity against Gram-positive bacteria, including drug-resistant pathogens. MICs of oritavancin, metronidazole and vancomycin for genotypically distinct C. difficile strains, including epidemic C. difficile PCR ribotypes 001 and 027, were determined by agar incorporation and broth macrodilution methods. In agar incorporation methods, the impact of supplements on oritavancin MICs was tested to address oritavancin binding to surfaces. METHODS: Thirty-three genotypically distinct C. difficile strains were identified by PCR ribotyping. Wilkins Chalgren agar incorporation plates containing oritavancin, metronidazole and vancomycin were prepared with and without 0.002% polysorbate-80 (P80) and lysed horse blood (2%). Broth macrodilution MICs of oritavancin, metronidazole and vancomycin were determined in Brucella broth. Inoculated agar incorporation plates and broth macrodilution tubes were cultured anaerobically at 37 degrees C for 48 h. RESULTS: Broth macrodilution MICs were lower than agar incorporation MICs for oritavancin, but not for metronidazole and vancomycin. Oritavancin broth macrodilution MIC(90)s were 2- to 4-fold lower than the corresponding agar incorporation MIC(90)s, while geometric mean MICs were >5-fold lower. Oritavancin broth macrodilution MIC(90)s were approximately 2- and 5-fold lower than those for metronidazole and vancomycin. Metronidazole was the most active antimicrobial agent against C. difficile using agar incorporation methods. Oritavancin agar incorporation MIC(90)s were unaffected by 0.002% P80 and/or 2% lysed horse blood. CONCLUSIONS: Oritavancin was at least 4-fold more potent than vancomycin against the majority (25/33) of C. difficile strains tested by broth macrodilution. Oritavancin activity may be underestimated by agar incorporation methods, regardless of the use of P80 or lysed horse blood. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/18606787/In_vitro_susceptibility_of_genotypically_distinct_and_clonal_Clostridium_difficile_strains_to_oritavancin_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkn276 DB - PRIME DP - Unbound Medicine ER -