title: Adaptive Cross-Resistance to Aminoglycoside Antibiotics in Pseudomonas aeruginosa Induced by Topical Dosage of Neomycin.
abstract: BACKGROUND
  Topical antimicrobial formulations containing neomycin are commonly used to prevent and treat burn infections. However, Pseudomonas aeruginosa shows rapid acquisition of adaptive resistance to neomycin. This study aimed to evaluate the survival of P. aeruginosa during exposure to neomycin at high concentrations comparable to those used in topical formulations, and to investigate the effect of adaptive resistance to neomycin on the susceptibility to other aminoglycosides.
  
  
  METHODS
  Strain IID1130 [neomycin minimal inhibitory concentration (MIC) = 4 µg/ml] was incubated on an agar medium containing neomycin at high concentrations (8-4,096 µg/ml), and growing colonies were macroscopically observed. Acquisition of adaptive resistance was examined for 5 P. aeruginosa strains. Cells were sequentially passaged on agar medium containing neomycin with step-wise increased concentrations (8-2,048 µg/ml). To assess reversion of antibiotic susceptibility, the resulting colonies were repeatedly subcultured on antibiotic-free agar plates.
  
  
  RESULTS
  Growing IID1130 colonies were macroscopically detected on a neomycin-containing (2,048 µg/ml) agar plate for 48 h. These cells showed increasing MIC for not only neomycin, but also gentamicin and amikacin; the MIC values were occasionally higher than the breakpoints. When the adapted cells were subcultured on antibiotic-free agar, several passages were required for reversion of susceptibility.
  
  
  CONCLUSIONS
  Our findings suggest that P. aeruginosa can survive in the presence of neomycin with a concentration typically used in topical dosage forms, and that the acquired adaptive resistance is persistent and is accompanied by cross-resistance to other aminoglycosides.
authors: Department of Emergency Medicine, Sapporo Medical University Hospital, Sapporo, Japan.
authors: Shuji
authors: S
authors: Uemura
authors: Shin-Ichi
authors: SI
authors: Yokota
authors: Tsukasa
authors: T
authors: Shiraishi
authors: Manabu
authors: M
authors: Kitagawa
authors: Suguru
authors: S
authors: Hirayama
authors: Ryoko
authors: R
authors: Kyan
authors: Hirotoshi
authors: H
authors: Mizuno
authors: Keigo
authors: K
authors: Sawamoto
authors: Hiroyuki
authors: H
authors: Inoue
authors: Atsushi
authors: A
authors: Miyamoto
authors: Eichi
authors: E
authors: Narimatsu
mesh_terms: D000287:Administration, Topical; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D009355:Neomycin / Q000008:administration & dosage*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D009355:Neomycin