Skip to content

Research at St Andrews

Repurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains of Klebsiella pneumoniae.

Research output: Contribution to journalArticlepeer-review

DOI

Open Access Status

  • Embargoed (until 14/10/21)

Author(s)

Alexandra E DeSarno, Benjamin John Parcell, Peter John Coote

School/Research organisations

Abstract

Multi-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections. Two MDR K. pneumoniae strains were employed, producing either the NDM-1 or KPC-3 carbapenemase. Efficacy of combinations of AZT with meropenem were compared with monotherapies against infections in Galleria mellonella larvae by measuring larval mortality and bacterial burden. The effect of the same combinations in vitro was determined via checkerboard and time-kill assays. In vitro, both K. pneumoniae strains were resistant to meropenem but were susceptible to AZT. In G. mellonella, treatment with either AZT or meropenem alone offered minimal therapeutic benefit against infections with either strain. In contrast, combination therapy of AZT with meropenem presented significantly enhanced efficacy compared to monotherapies. This was correlated with prevention of bacterial proliferation within the larvae but not elimination. Checkerboard assays showed that the interaction between AZT and meropenem was not synergistic but indifferent. In summary, combination therapy of AZT with meropenem represents a potential treatment for carbapenemase-producing MDR K. pneumoniae and merits further investigation.
Close

Details

Original languageEnglish
JournalPathogens and Disease
VolumeAdvance Article
Early online date14 Oct 2020
DOIs
Publication statusE-pub ahead of print - 14 Oct 2020

    Research areas

  • Klebsiella pneumoniae, Galleria mellonella, Wax-moth larvae, Combination therapy, NDM1, KPC3

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. In vivo safety assessment of rhodomyrtone, a potent compound, from Rhodomyrtus tomentosa leaf extract

    Siriyong, T., Ontong, J. C., Leejae, S., Suwalak, S., Coote, P. J. & Voravuthikunchai, S. P., 31 Jul 2020, In: Toxicology Reports. 7, p. 919-924 6 p.

    Research output: Contribution to journalArticlepeer-review

  2. Dual β-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection: enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition

    Siriyong, T., Murray, R. M., Bidgood, L. E., Young, S. A., Wright, F., Parcell, B. J., Voravuthikunchai, S. P. & Coote, P. J., 24 Jun 2019, In: Scientific Reports. 9, 13 p., 9098.

    Research output: Contribution to journalArticlepeer-review

ID: 270640316

Top