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Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii

Thien B Tran1, Soon-Ee Cheah1, Heidi H Yu1

  • 1Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.

The Journal of Antibiotics
|December 17, 2015
PubMed

Insights

The combination of polymyxin B and closantel shows promise for treating multidrug-resistant Acinetobacter baumannii infections. This novel approach may overcome resistance to polymyxins, offering a new strategy against challenging bacterial superbugs.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Polymyxins are last-resort antibiotics for multidrug-resistant (MDR) Acinetobacter baumannii.
  • Monotherapy with polymyxins can lead to the development of resistance, necessitating novel therapeutic strategies.
  • There is an urgent need to preserve and enhance the efficacy of polymyxins against resistant bacterial strains.

Purpose of the Study:

  • To investigate the antimicrobial activity of a novel combination of polymyxin B and the anthelmintic drug closantel against Acinetobacter baumannii.
  • To evaluate the potential of this combination in overcoming polymyxin resistance in A. baumannii isolates.

Main Methods:

  • Testing the efficacy of closantel monotherapy against A. baumannii isolates.
  • Assessing the synergistic effect of combining polymyxin B (at clinically achievable concentrations) with varying concentrations of closantel.
  • Evaluating the combination's ability to inhibit resistance development in susceptible isolates and provide synergistic killing against resistant isolates.

Main Results:

  • Closantel monotherapy was largely ineffective against most tested A. baumannii isolates.
  • The combination of polymyxin B with closantel (4-16 mg/L) inhibited the development of polymyxin resistance in susceptible isolates.
  • Synergistic killing was observed against polymyxin-resistant A. baumannii isolates when treated with the combination therapy.

Conclusions:

  • The combination of polymyxin B and closantel demonstrates potential for treating MDR, including polymyxin-resistant, Acinetobacter baumannii infections.
  • Repurposing non-antibiotic drugs like closantel offers a promising avenue for discovering new treatments against bacterial superbugs.
  • This combination therapy could be a valuable strategy to preserve the effectiveness of polymyxins as a last-line antibiotic class.

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