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Published on: April 18, 2019

The activity of 14-hydroxy clarithromycin, alone and in combination with clarithromycin, against penicillin- and

S J Martin1, C G Garvin, C R McBurney

  • 1The Infectious Diseases Research Laboratory at The University of Toledo, College of Pharmacy, 2801 W. Bancroft Street, Toledo, OH 43606, USA. smartin2@pop3.utoledo.edu

The Journal of Antimicrobial Chemotherapy
|May 1, 2001
PubMed

Insights

The active metabolite of clarithromycin, 14-hydroxy clarithromycin, shows potent activity against Streptococcus pneumoniae. Combining clarithromycin with its metabolite enhances antibacterial efficacy, especially against resistant strains.

Area of Science:

  • Pharmacology and Microbiology
  • Antimicrobial Resistance
  • Drug Metabolism

Background:

  • Limited data exist on the activity of 14-hydroxy clarithromycin against resistant Streptococcus pneumoniae strains.
  • Understanding clarithromycin's metabolite activity is crucial for accurate in vitro susceptibility testing.
  • Penicillin-intermediate and resistant Streptococcus pneumoniae pose significant therapeutic challenges.

Purpose of the Study:

  • To evaluate the in vitro activity of 14-hydroxy clarithromycin against various Streptococcus pneumoniae strains.
  • To assess the synergistic or additive effects of combining clarithromycin with its metabolite.
  • To determine the bactericidal activity of the clarithromycin-metabolite combination.

Main Methods:

  • Agar dilution Minimum Inhibitory Concentrations (MICs) were determined for clarithromycin, its metabolite, azithromycin, and erythromycin.
  • Agar chequerboard assays assessed drug interactions, and time-kill tests evaluated bactericidal activity.
  • Testing included penicillin-intermediate, penicillin-resistant, and erythromycin-resistant Streptococcus pneumoniae isolates.

Main Results:

  • 14-hydroxy clarithromycin demonstrated potent activity against Streptococcus pneumoniae isolates.
  • Clarithromycin/metabolite combinations showed lower MICs than clarithromycin alone in many strains.
  • Synergy was observed in 13 strains, and the combination was more rapidly bactericidal than clarithromycin alone in most tested isolates.

Conclusions:

  • 14-hydroxy clarithromycin possesses significant intrinsic activity against Streptococcus pneumoniae.
  • The metabolite enhances the activity of clarithromycin, particularly against resistant strains.
  • In vitro susceptibility testing should account for the metabolite's activity to avoid underestimating clarithromycin's efficacy.

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