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Resistance studies with Streptococcus pneumoniae using an in vitro dynamic model: amoxicillin versus azithromycin at

Maria V Golikova1, Elena N Strukova1, Yury A Portnoy1

  • 1Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics , Moscow , Russia.

Journal of Chemotherapy (Florence, Italy)
|June 11, 2019
PubMed

Insights

Emergence of Streptococcus pneumoniae resistance to azithromycin, but not amoxicillin, was observed in vitro. This suggests azithromycin resistance may develop more readily under typical dosing conditions compared to amoxicillin.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Limited understanding of Streptococcus pneumoniae resistance development during aminopenicillin and macrolide treatment.
  • Lack of correlation between clinical isolation of azithromycin-resistant mutants and actual blood antibiotic concentrations.

Purpose of the Study:

  • To investigate the selection of amoxicillin- and azithromycin-resistant S. pneumoniae mutants under therapeutic and subtherapeutic antibiotic exposures.
  • To compare the enrichment of resistant mutants in an in vitro dynamic model simulating different antibiotic concentrations.

Main Methods:

  • Utilized an in vitro dynamic model to simulate antibiotic exposures.
  • Exposed Streptococcus pneumoniae to varying concentrations of amoxicillin and azithromycin.
  • Monitored the enrichment of resistant mutants throughout the simulations.

Main Results:

  • No enrichment of amoxicillin-resistant S. pneumoniae mutants was observed.
  • Azithromycin-resistant S. pneumoniae mutants were enriched in all simulations.
  • Differences in resistance selection were linked to time above the mutant prevention concentration (MPC).

Conclusions:

  • Findings support the mutant selection window hypothesis.
  • Amoxicillin exposure maintained concentrations above the MPC for longer durations, inhibiting resistance.
  • Azithromycin exposure frequently fell below the MPC, facilitating the selection of resistant mutants.
Keywords:
AmoxicillinAzithromycinResistantin vitro dynamic model

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