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Published on: April 18, 2019
Effect of Meropenem, Sulbactam, and Colistin Combinations on Resistance Gene Expression in Multidrug-Resistant A.
José Emigdio Moreno1,2, Jordi Querol-Audi3,4, Ariel Magallón Tejada5
1Doctorate in Biosciences and Biotechnology, Faculty of Science and Technology, Universidad Tecnológica de Panamá, Panama City 0819-07289, Panama.
Background:
Given the increasing problem of antibiotic resistance in A. baumannii, this study examines in vitro how combinations of colistin, meropenem, and sulbactam influence the expression of genes associated with multiresistance in this pathogen.
Methods:
Three multidrug-resistant strains, isolated from clinical infections in Panama (2022-2023), were identified using Vitek 2 compact. Susceptibility by broth microdilution, qualitative synergy, time-kill curves, and gene expression analysis by quantitative PCR were performed.
Results:
Synergistic effects were observed for the colistin-meropenem combination in all three strains, while the sulbactam-colistin combination exhibit synergy only in one of the A. baumannii isolates. Time-kill assays revealed bactericidal effects for the colistin-meropenem and sulbactam-colistin combinations. qPCR analyses indicated that colistin, meropenem, and sulbactam modified the expression of the genes under study. Colistin-meropenem and meropenem-sulbactam combinations decreased the expression of blaADC and blaOXA-51, while sulbactam-colistin did not have a significant effect. carO expression levels were not reduced with any antibiotic combination, while adeB expression was reduced with all the combinations tested. omp33-36 expression varied depending on the antibiotic and strain.
Conclusions:
Therefore, this study offers a new perspective on how rational combinations of clinically used antibiotics have the potential to modulate gene expression and contribute to the control of MDR strains, indicating that high-dose combination therapy with sulbactam and colistin could offer improved efficacy in treating multidrug resistant Acinetobacter baumannii infections.
Insights
Combinations of colistin, meropenem, and sulbactam can reduce multidrug resistance gene expression in Acinetobacter baumannii. This suggests potential for high-dose combination therapy to combat resistant infections.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Background:
- Antibiotic resistance in Acinetobacter baumannii is a growing global health concern.
- Understanding the molecular mechanisms of resistance is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the in vitro effects of colistin, meropenem, and sulbactam combinations on the expression of multidrug resistance genes in Acinetobacter baumannii.
- To evaluate the synergistic and bactericidal potential of these antibiotic combinations.
Main Methods:
- Three multidrug-resistant Acinetobacter baumannii strains were used.
- Methods included Vitek 2 identification, broth microdilution, time-kill curves, and quantitative PCR for gene expression analysis.
Main Results:
- Colistin-meropenem demonstrated synergistic effects in all strains and bactericidal activity.
- Colistin-meropenem and meropenem-sulbactam combinations reduced blaADC and blaOXA-51 gene expression.
- All tested combinations reduced adeB expression, while omp33-36 expression varied.
Conclusions:
- Rational antibiotic combinations can modulate gene expression and aid in controlling multidrug-resistant strains.
- High-dose combination therapy with sulbactam and colistin may enhance efficacy against multidrug-resistant Acinetobacter baumannii infections.
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