Susceptibility of Methicillin-Resistant Staphylococcus aureus to Five Quinazolinone Antibacterials

Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01344-19. doi: 10.1128/AAC.01344-19. Print 2019 Dec 20.

Abstract

The in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5. Several strains with high MIC values (from 8 to >32 μg/ml) for some of these compounds exhibited amino acid changes in the penicillin-binding proteins, which are targeted by these antibacterials.

Keywords: MRSA; methicillin-resistant Staphylococcus aureus; penicillin-binding proteins; quinazolinones; staphylococci.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Microbial Sensitivity Tests
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Spain
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Penicillin-Binding Proteins
  • Quinazolinones