Infection and Drug Resistance (Mar 2024)

The Potentiation Activity of Azithromycin in Combination with Colistin or Levofloxacin Against Pseudomonas aeruginosa Biofilm Infection

  • Wang Y,
  • Li C,
  • Zhang H,
  • Chi Y,
  • Cai Y

Journal volume & issue
Vol. Volume 17
pp. 1259 – 1266

Abstract

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Yuhang Wang,1,* Chunsun Li,2,* Huan Zhang,1 Yulong Chi,1 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, People’s Republic of China; 2Laboratory of Department of Pulmonary and Critical Care Medicine, PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Cai, Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies center of PLA General Hospital, Postal Address: 28 Fu Xing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-6693-7166, Fax +86-10-8821-4425, Email [email protected]: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens.Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system.Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin–colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day.Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.Keywords: Pseudomonas aeruginosa, biofilm, azithromycin, combinations

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