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

Thanyaluck Siriyong, Rachael M. Murray, Lucy E. Bidgood, Simon A. Young, Florence Wright, Benjamin J. Parcell, Supayang Piyawan Voravuthikunchai, Peter J. Coote (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    2 Citations (Scopus)
    91 Downloads (Pure)

    Abstract

    The aim of the study was to determine the efficacy of dual β-lactam combination treatments derived from eight approved drugs against Galleria mellonella larvae infected with MDR strains of P. aeruginosa. Carbapenem-resistant P. aeruginosa NCTC 13437 and an unrelated clinical isolate were used to infect G. mellonella larvae and the efficacy of twenty-eight dual β-lactam combination therapies were compared to their constituent monotherapies. For the most potent combinations identified, penicillin-binding protein (PBP) inhibition profiles were measured and compared with each constituent antibiotic. Five of the dual β-lactam combinations resulted in greater than 70% survival of infected G. mellonella. Two combinations showed potent, enhanced efficacy versus both strains − ceftazidime + meropenem and aztreonam + meropenem. Comparison of PBP inhibition profiles revealed that the enhanced efficacy of these two dual β-lactam combinations could not be explained by more potent inhibition of PBPs or inhibition of a broader range of PBPs. A possible contribution to the enhanced efficacy of the combinations could be stimulation of innate immunity via increased haemocyte numbers compared to their constituent monotherapies. Combinations of β-lactam antibiotics show promise in overcoming MDR P. aeruginosa and are worthy of additional study and development.

    Original languageEnglish
    Article number9098
    Pages (from-to)1-13
    Number of pages13
    JournalScientific Reports
    Volume9
    DOIs
    Publication statusPublished - 24 Jun 2019

    Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this