title: [Effects of antibiotics plus efflux pump inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro].
abstract: OBJECTIVE
  To explore the effects of antibiotics plus efflux pump (EPI) inhibitors on mutant selection window of Pseudomonas aeruginosa in vitro.
  
  
  METHODS
  In standard strains, the minimum inhibitory concentrations (MICs) of meropenem, ceftazidime, amikacin and ciprofloxacin alone were measured. Then the MICs of four antibiotics respectively plus EPI, including reserpine, omeprazole, azithromycin, carbonyl cyanide m-chlorophenyl- hydrazone (CCCP) and Phe-Arg-β-naphtylamide (PAβN), were measured by checkerboard test. And the mutant prevention concentrations (MPC) of antibiotics alone and antibiotics plus different EPIs were also measured by agar dilution method. Selection indices (SI) were acquired through MPC divided by MIC. Similarly, the SI of meropenem, ceftazidime and ciprofloxacin which respectively plus amikacin and amikacin plus ciprofloxacin were measured. In clinical strains, MIC, MPC and SI of antibiotics alone and four antibiotics plus CCCP were measured.
  
  
  RESULTS
  In standard strains, the SI of meropenem, ceftazidime, amikacin and ciprofloxacin alone were >32, >32, 16 and 16. After adding EPI, the SI of four antibiotics were 16, 16, 16, 8 (reserpine), 16, 32, 16, 8 (omeprazole), 8, 16, 16, 8 (azithromycin), 8, 8, 16, 8 (CCCP) and 8, 16, 16, 8 (PAβN). The SI of meropenem, ceftazidime and ciprofloxacin plus amikacin were 4, 4, 8. And the SI of amikacin plus ciprofloxacin was 4. In clinical strains, the SI of ciprofloxacin significantly decreased after adding CCCP.
  
  
  CONCLUSIONS
  Both MIC and MPC of meropenem, ceftazidime and ciprofloxacin decreased significantly after adding EPI. The mutant selection window decreased when ciprofloxacin was combined with CCCP.
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Xu
authors.forename: Mingtao
authors.initials: M
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Email: qlliyu@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000583:Amikacin; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002939:Ciprofloxacin; D004151:Dipeptides; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013845:Thienamycins
chemical_list: D000904:Antibiotics, Antitubercular; D004151:Dipeptides; D013845:Thienamycins; C048251:phenylalanylarginine; D002939:Ciprofloxacin; D000583:Amikacin; D000077731:Meropenem