In vitro activity of the ketolide cethromycin in multidrug-resistant clinical Neisseria gonorrhoeae isolates and international reference strains

J Chemother. 2019 Sep;31(5):246-251. doi: 10.1080/1120009X.2019.1615724. Epub 2019 May 20.

Abstract

Antimicrobial resistance in Neisseria gonorrhoeae is a major public health problem, which compromises the treatment of gonorrhoea globally. We evaluated the in vitro activity of the ketolide cethromycin against a large panel of clinical gonococcal isolates and international reference strains (n = 254), including numerous multidrug-resistant and extensively drug-resistant isolates. Cethromycin showed potent in vitro activity against most of the gonococcal isolates with the following modal MIC, MIC50 and MIC90: 0.064 mg/L, 0.125 mg/L and 0.5 mg/L, respectively. However, cross-resistance between azithromycin and cethromycin was identified (Spearman's rank correlation coefficient 0.917) and isolates displaying high-level resistance to azithromycin (MIC >256 mg/L; n = 9) also showed high MICs of cethromycin (32-256 mg/L). In conclusion, the cross-resistance with azithromycin indicates that cethromycin may not be considered for empirical first-line monotherapy of gonorrhoea. However, cethromycin might be valuable in combination antimicrobial therapy and for second-line therapy e.g. for cases with ceftriaxone resistance or allergy.

Keywords: ABT-773; antimicrobial resistance; cethromycin; gonorrhoea; ketolide; treatment.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Gonorrhea / drug therapy*
  • Gonorrhea / microbiology
  • Humans
  • In Vitro Techniques
  • Ketolides / pharmacology*
  • Microbial Sensitivity Tests
  • Neisseria gonorrhoeae / classification
  • Neisseria gonorrhoeae / drug effects*
  • Neisseria gonorrhoeae / isolation & purification*
  • Reference Standards

Substances

  • Anti-Bacterial Agents
  • Ketolides
  • cethromycin