title: In vitro activity of surotomycin against contemporary clinical isolates of toxigenic Clostridium difficile strains obtained in Spain.
abstract: OBJECTIVE
  Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhoea in developed countries. Metronidazole and vancomycin are the mainstay of treatment, although they are associated with treatment failure and recurrence. Novel agents have emerged to address these shortcomings. We investigated the in vitro activity of a novel agent, surotomycin (formerly CB-183,315), and seven other antimicrobial agents against clinical C. difficile isolates.
  
  
  METHODS
  Antimicrobial susceptibility to surotomycin, fidaxomicin, metronidazole, vancomycin, clindamycin, rifaximin, moxifloxacin and tigecycline was determined for 100 contemporary clinical isolates of C. difficile collected in 2013. MICs were determined by agar dilution according to CLSI procedures. In addition, 10 strains with reduced susceptibility to metronidazole (n = 6) and vancomycin (n = 4) were also tested. Strains were PCR ribotyped.
  
  
  RESULTS
  The MICs of surotomycin for the 100 isolates ranged from ≤0.06 to 2 mg/L, with a geometric mean (GM) of 0.31 mg/L and an MIC50/90 of 0.25/0.5 mg/L. The MIC range of surotomycin was 0.25-1 mg/L (GM = 0.45 mg/L) for isolates with reduced metronidazole susceptibility and 0.125-0.5 mg/L (GM = 0.25 mg/L) for isolates with reduced vancomycin susceptibility. The three most common ribotypes were 001 (31.0%), 014/020 (17.0%) and 078/126 (17.0%). Ribotype 014/020 exhibited the lowest MICs of surotomycin (GM = 0.22 mg/L); the highest MICs were for ribotype 078/126 (GM = 0.72 mg/L).
  
  
  CONCLUSIONS
  Surotomycin exhibited potent in vitro activity against all the isolates tested, including those with elevated metronidazole and vancomycin MICs. The potential role of this agent in the treatment of CDI requires further clinical evaluation.
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain helenrei@hotmail.com.
authors: E
authors: E
authors: Reigadas
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: L
authors: L
authors: Alcalá
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: M
authors: M
authors: Marín
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: T
authors: T
authors: Pelaéz
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors: A
authors: A
authors: Martin
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: C
authors: C
authors: Iglesias
authors: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain Medicine Department, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0058), Madrid, Spain.
authors: E
authors: E
authors: Bouza
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003015:Clostridium Infections / Q000382:microbiology; D005260:Female; D005838:Genotype; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology*; D021521:Ribotyping; D013030:Spain; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; C574454:CB-183,315; D055666:Lipopeptides; D010456:Peptides, Cyclic
keywords: C. difficile; antimicrobial susceptibility; fidaxomicin; ribotype