In vitro synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii grown in planktonic phase and in biofilms

Simona Pollini, Selene Boncompagni, Tiziana DI Maggio, Vincenzo DI Pilato, Teresa Spanu, Barbara Fiori, Francesco Blasi, Stefano Aliberti, Francesco Sergio, Gian Maria Rossolini, Lucia Pallecchi

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Abstract

Objectives: To investigate the potential synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii strains grown in planktonic phase or as biofilms. Methods: Sixteen strains were investigated, including nine colistin-susceptible (MIC range 0.5-1 mg/L) and seven colistin-resistant (MIC range 16-256 mg/L) strains. Synergism of colistin in combination with N-acetylcysteine was investigated by chequerboard assays. The activity of colistin/N-acetylcysteine combinations was further evaluated by time-kill assays with planktonic cultures (three colistin-resistant strains and one colistinsusceptible strain) and by in vitro biofilm models (three colistin-resistant and three colistin-susceptible strains). Results: Chequerboard assays revealed a relevant synergism of colistin/N-acetylcysteine combinations with all colistin-resistant strains, whereas no synergism was observed with colistin-susceptible strains. Time-kill assays showed a concentration-dependent potentiation of colistin activity by N-acetylcysteine against colistin-resistant strains, with eradication of the culture by combinations of N-acetylcysteine at 8000 mg/L plus colistin at 2 or 8 mg/L. A static effect during the first 8 h of incubation was demonstrated with the colistin-susceptible strain exposed to 0.25×MIC colistin plus 8000 mg/L N-acetylcysteine. A remarkable antibiofilm synergistic activity of 8 mg/L colistin plus 8000 mg/L N-acetylcysteine was demonstrated with all colistin-resistant and colistinsusceptible strains. The effects were greater with colistin-resistant strains (marked reduction of viable biofilm cells was observed at sub-MIC colistin concentrations). Conclusions: N-acetylcysteine, at concentrations achievable by topical administration, was shown to revert the colistin-resistant phenotype in A. baumannii, and to exert a relevant activity against biofilms of colistin susceptible and colistin-resistant A. baumannii strains.

Original languageEnglish
Pages (from-to)2388-2395
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number9
DOIs
Publication statusPublished - Jan 1 2018

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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    Pollini, S., Boncompagni, S., DI Maggio, T., DI Pilato, V., Spanu, T., Fiori, B., Blasi, F., Aliberti, S., Sergio, F., Rossolini, G. M., & Pallecchi, L. (2018). In vitro synergism of colistin in combination with N-acetylcysteine against Acinetobacter baumannii grown in planktonic phase and in biofilms. Journal of Antimicrobial Chemotherapy, 73(9), 2388-2395. https://doi.org/10.1093/jac/dky185