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. 2015;70(6):1751-6.
doi: 10.1093/jac/dkv006. Epub 2015 Feb 3.

In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile

D Corbett  1 , A Wise  1 , S Birchall  1 , P Warn  1 , S D Baines  2 , G Crowther  3 , J Freeman  3 , C H Chilton  3 , J Vernon  3 , M H Wilcox  3 , R J Vickers  4
Affiliations

In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile

D Corbett et al. J Antimicrob Chemother. 2015.

Abstract

Objectives: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile.

Methods: MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively).

Results: SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested.

Conclusions: These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.

Keywords: C. difficile; PAE; antimicrobial.

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Figures

Figure 1.
Figure 1.
Twenty-four hour time–kill curves for vancomycin against C. difficile BI1. Data are the means (+SD) of triplicate experiments.
Figure 2.
Figure 2.
Twenty-four hour time–kill curves for fidaxomicin against C. difficile BI1. Data are the means (+SD) of triplicate experiments.
Figure 3.
Figure 3.
Twenty-four hour time–kill curves for SMT19969 against C. difficile BI1. Data are the means (+SD) of triplicate experiments.
Figure 4.
Figure 4.
PAE of SMT19969 against C. difficile BI1. Data are the means (+SD) of triplicate experiments. Drug removed at 0 h.
See this image and copyright information in PMC

References

    1. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009; 7: 526–36. - PubMed
    1. Kelly CP, Lamont JT. Clostridium difficile—more difficult than ever. New Engl J Med 2008; 359: 1932–40. - PubMed
    1. He M, Miyajima F, Roberts P, et al. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nat Genet 2013; 45: 109–13. - PMC - PubMed
    1. Tickler IA, Goering RV, Whitmore JD, et al. Strain types and antimicrobial resistance patterns of Clostridium difficile isolates from the United States, 2011 to 2013. Antimicrob Agents Chemother 2014; 58: 4214–8. - PMC - PubMed
    1. Petrella LA, Sambol SP, Cheknis A, et al. Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain. Clin Infect Dis 2012; 55: 351–7. - PMC - PubMed

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