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

Thien B. Tran, Soon Ee Cheah, Heidi H. Yu, Phillip J. Bergen, Roger L. Nation, Darren J. Creek, Anthony Purcell, Alan Forrest, Yohei Doi, Jiangning Song, Tony Velkov, Jian Li

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l-1) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l-1 with a clinically achievable concentration of polymyxin B (2 mg l-1) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ≥4 mg l-1). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-Antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'.

Original languageEnglish
Pages (from-to)415-421
Number of pages7
JournalJournal of Antibiotics
Volume69
Issue number6
DOIs
Publication statusPublished - 01-06-2016

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Polymyxins
Acinetobacter baumannii
Polymyxin B
Anthelmintics
Acinetobacter Infections
Anti-Bacterial Agents
Bacterial Infections
Pharmacokinetics
closantel
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Tran, T. B., Cheah, S. E., Yu, H. H., Bergen, P. J., Nation, R. L., Creek, D. J., ... Li, J. (2016). Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii. Journal of Antibiotics, 69(6), 415-421. https://doi.org/10.1038/ja.2015.127
Tran, Thien B. ; Cheah, Soon Ee ; Yu, Heidi H. ; Bergen, Phillip J. ; Nation, Roger L. ; Creek, Darren J. ; Purcell, Anthony ; Forrest, Alan ; Doi, Yohei ; Song, Jiangning ; Velkov, Tony ; Li, Jian. / Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii. In: Journal of Antibiotics. 2016 ; Vol. 69, No. 6. pp. 415-421.
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Tran, TB, Cheah, SE, Yu, HH, Bergen, PJ, Nation, RL, Creek, DJ, Purcell, A, Forrest, A, Doi, Y, Song, J, Velkov, T & Li, J 2016, 'Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii', Journal of Antibiotics, vol. 69, no. 6, pp. 415-421. https://doi.org/10.1038/ja.2015.127

Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii. / Tran, Thien B.; Cheah, Soon Ee; Yu, Heidi H.; Bergen, Phillip J.; Nation, Roger L.; Creek, Darren J.; Purcell, Anthony; Forrest, Alan; Doi, Yohei; Song, Jiangning; Velkov, Tony; Li, Jian.

In: Journal of Antibiotics, Vol. 69, No. 6, 01.06.2016, p. 415-421.

Research output: Contribution to journalArticle

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T1 - Anthelmintic closantel enhances bacterial killing of polymyxin B against multidrug-resistant Acinetobacter baumannii

AU - Tran, Thien B.

AU - Cheah, Soon Ee

AU - Yu, Heidi H.

AU - Bergen, Phillip J.

AU - Nation, Roger L.

AU - Creek, Darren J.

AU - Purcell, Anthony

AU - Forrest, Alan

AU - Doi, Yohei

AU - Song, Jiangning

AU - Velkov, Tony

AU - Li, Jian

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l-1) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l-1 with a clinically achievable concentration of polymyxin B (2 mg l-1) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ≥4 mg l-1). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-Antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'.

AB - Polymyxins, an old class of antibiotics, are currently used as the last resort for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii. However, recent pharmacokinetic and pharmacodynamic data indicate that monotherapy can lead to the development of resistance. Novel approaches are urgently needed to preserve and improve the efficacy of this last-line class of antibiotics. This study examined the antimicrobial activity of novel combination of polymyxin B with anthelmintic closantel against A. baumannii. Closantel monotherapy (16 mg l-1) was ineffective against most tested A. baumannii isolates. However, closantel at 4-16 mg l-1 with a clinically achievable concentration of polymyxin B (2 mg l-1) successfully inhibited the development of polymyxin resistance in polymyxin-susceptible isolates, and provided synergistic killing against polymyxin-resistant isolates (MIC ≥4 mg l-1). Our findings suggest that the combination of polymyxin B with closantel could be potentially useful for the treatment of MDR, including polymyxin-resistant, A. baumannii infections. The repositioning of non-Antibiotic drugs to treat bacterial infections may significantly expedite discovery of new treatment options for bacterial 'superbugs'.

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