ArticleScientific reports2019
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.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Management of Ventilator-Associated Pneumonia Caused byMedicina (Kaunas, Lithuania) · 2024Trial
- TACTIC: A transfer learning framework to predict drug interactions in emerging pathogens.Cell reports methods · 2026Article
- Optimizing target inactivation to treat multidrug-resistantAntimicrobial agents and chemotherapy · 2026Article
- Integrating Modified FeCurrent microbiology · 2025Article
- Article
- Transfer learning predicts species-specific drug interactions in emerging pathogens.bioRxiv : the preprint server for biology · 2024Article
- Investigating Combination Therapy as a Means to Enhance Activity and Repurpose Antimicrobials.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Penicillin-Binding Protein 5/6 Acting as a Decoy Target in Pseudomonas aeruginosa Identified by Whole-Cell Receptor Binding and Quantitative Systems Pharmacology.Antimicrobial agents and chemotherapy · 2023Article
- PBP Target Profiling by β-Lactam and β-Lactamase Inhibitors in Intact Pseudomonas aeruginosa: Effects of the Intrinsic and Acquired Resistance Determinants on the Periplasmic Drug Availability.Microbiology spectrum · 2023Article
- Carbapenem-Only Combination Therapy against Multi-Drug ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Live-Cell Profiling of Penicillin-Binding Protein Inhibitors inACS infectious diseases · 2022Article
- β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward.Frontiers in microbiology · 2022Review
- Global Threat of Carbapenem-Resistant Gram-Negative Bacteria.Frontiers in cellular and infection microbiology · 2022Review
- Infectious disease: how to manage Gram-positive and Gram-negative pathogen conundrums with dual beta-lactam therapy.Drugs in context · 2022Review
- β-lactam Resistance inPathogens (Basel, Switzerland) · 2021Review
- Losing the Battle but Winning the War: Can Defeated Antibacterials Form Alliances to Combat Drug-Resistant Pathogens?Antibiotics (Basel, Switzerland) · 2021Review
- Combating Multidrug-Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling.Clinical pharmacology and therapeutics · 2021Article
- Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance.Frontiers in chemistry · 2021Review
- Analysis of Metallo-β-lactamases, oprD Mutation, and Multidrug Resistance of β-lactam Antibiotic-Resistant Strains of Pseudomonas aeruginosa Isolated from Southern China.Current microbiology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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