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
| Autor: | Thanyaluck Siriyong, Rachael M. Murray, Benjamin J. Parcell, Simon A. Young, Lucy E. Bidgood, Florence Wright, Supayang Piyawan Voravuthikunchai, Peter J. Coote |
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| Přispěvatelé: | University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex, University of St Andrews. School of Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Penicillin binding proteins Combination therapy medicine.drug_class Antibiotics NDAS lcsh:Medicine Drug resistance Pharmacology beta-Lactams medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine In vivo medicine polycyclic compounds Animals Humans Penicillin-Binding Proteins Drug Interactions Pseudomonas Infections lcsh:Science R2C Multidisciplinary Innate immune system biology Pseudomonas aeruginosa Chemistry fungi lcsh:R QR Microbiology biochemical phenomena metabolism and nutrition biology.organism_classification Survival Analysis Drug Resistance Multiple Anti-Bacterial Agents QR Experimental models of disease Lepidoptera Galleria mellonella 030104 developmental biology bacteria lcsh:Q Pathogens BDC 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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