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Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile.
J Med Microbiol. 2018 Sep; 67(9):1402-1409.JM

Abstract

PURPOSE

Clostridium difficile infection (CDI) is an increasing cause of nosocomial diarrhoea worldwide, which has been partly attributed to the emergence of hypervirulent strains including C. difficile BI/NAP1/ribotype 027 and BK/NAP7/ribotype 078. Cadazolid is a new antibiotic currently in late-stage clinical studies for the treatment of CDI. The present study evaluated the in vitro bactericidal effect of cadazolid and comparator antibiotics against four C. difficile strains. The data demonstrate the potent and bactericidal activity of cadazolid against different ribotypes of C. difficile.

METHODOLOGY

MICs for test antibiotics were determined in brain- heart infusion-supplemented broth (BHIS) containing 5 g l-1 yeast extract and 0.025 % (w/v) l-cysteine. Time-kill kinetics to investigate the rate of killing of each antibiotic at sub- and supra-MIC concentrations were performed at concentrations of 0.5, 1, 2, 4, 8 or 16× the MIC of cadazolid, vancomycin and fidaxomicin at intervals over a 48 h period.Results/key findings. Cadazolid-mediated killing of C. difficile was faster and occurred at lower concentrations than observed for vancomycin, while potency and killing was largely comparable to those observed for fidaxomicin. Notably, cadazolid also displayed a potent bactericidal effect against fluoroquinolone-resistant hypervirulent ribotype 027 and 078 strains. C. difficile spore formation was largely inhibited by all three antibiotics at concentrations >1× MIC; however, none were able to eliminate spores effectively, which were present at the start of the experiment.

CONCLUSION

The data presented here demonstrate the potent in vitro bactericidal activity of cadazolid against different ribotypes of C. difficile, although on a limited set of strains.

Authors+Show Affiliations

1​Evotec (UK), Alderley Park, Cheshire, SK10 4TG, UK.1​Evotec (UK), Alderley Park, Cheshire, SK10 4TG, UK.1​Evotec (UK), Alderley Park, Cheshire, SK10 4TG, UK.1​Evotec (UK), Alderley Park, Cheshire, SK10 4TG, UK.2​Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. †​Present address: Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30052178

Citation

Skinner, Kirsty, et al. "Time-kill Kinetics of Cadazolid and Comparator Antibacterial Agents Against Different Ribotypes of Clostridium Difficile." Journal of Medical Microbiology, vol. 67, no. 9, 2018, pp. 1402-1409.
Skinner K, Birchall S, Corbett D, et al. Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile. J Med Microbiol. 2018;67(9):1402-1409.
Skinner, K., Birchall, S., Corbett, D., Thommes, P., & Locher, H. H. (2018). Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile. Journal of Medical Microbiology, 67(9), 1402-1409. https://doi.org/10.1099/jmm.0.000808
Skinner K, et al. Time-kill Kinetics of Cadazolid and Comparator Antibacterial Agents Against Different Ribotypes of Clostridium Difficile. J Med Microbiol. 2018;67(9):1402-1409. PubMed PMID: 30052178.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile. AU - Skinner,Kirsty, AU - Birchall,Stephen, AU - Corbett,David, AU - Thommes,Pia, AU - Locher,Hans H, Y1 - 2018/07/27/ PY - 2018/7/28/pubmed PY - 2018/9/12/medline PY - 2018/7/28/entrez KW - CDI KW - Clostridium difficile KW - cadazolid KW - time-kill kinetics SP - 1402 EP - 1409 JF - Journal of medical microbiology JO - J. Med. Microbiol. VL - 67 IS - 9 N2 - PURPOSE: Clostridium difficile infection (CDI) is an increasing cause of nosocomial diarrhoea worldwide, which has been partly attributed to the emergence of hypervirulent strains including C. difficile BI/NAP1/ribotype 027 and BK/NAP7/ribotype 078. Cadazolid is a new antibiotic currently in late-stage clinical studies for the treatment of CDI. The present study evaluated the in vitro bactericidal effect of cadazolid and comparator antibiotics against four C. difficile strains. The data demonstrate the potent and bactericidal activity of cadazolid against different ribotypes of C. difficile. METHODOLOGY: MICs for test antibiotics were determined in brain- heart infusion-supplemented broth (BHIS) containing 5 g l-1 yeast extract and 0.025 % (w/v) l-cysteine. Time-kill kinetics to investigate the rate of killing of each antibiotic at sub- and supra-MIC concentrations were performed at concentrations of 0.5, 1, 2, 4, 8 or 16× the MIC of cadazolid, vancomycin and fidaxomicin at intervals over a 48 h period.Results/key findings. Cadazolid-mediated killing of C. difficile was faster and occurred at lower concentrations than observed for vancomycin, while potency and killing was largely comparable to those observed for fidaxomicin. Notably, cadazolid also displayed a potent bactericidal effect against fluoroquinolone-resistant hypervirulent ribotype 027 and 078 strains. C. difficile spore formation was largely inhibited by all three antibiotics at concentrations >1× MIC; however, none were able to eliminate spores effectively, which were present at the start of the experiment. CONCLUSION: The data presented here demonstrate the potent in vitro bactericidal activity of cadazolid against different ribotypes of C. difficile, although on a limited set of strains. SN - 1473-5644 UR - https://www.unboundmedicine.com/medline/citation/30052178/Time_kill_kinetics_of_cadazolid_and_comparator_antibacterial_agents_against_different_ribotypes_of_Clostridium_difficile_ L2 - http://jmm.microbiologyresearch.org/pubmed/content/journal/jmm/10.1099/jmm.0.000808 DB - PRIME DP - Unbound Medicine ER -