# Effect of Meropenem, Sulbactam, and Colistin Combinations on Resistance Gene Expression in Multidrug-Resistant A. baumannii Clinical Isolates from Panama

## TL;DR

This study explores how combining antibiotics affects gene expression in drug-resistant Acinetobacter baumannii from Panama, finding that some combinations reduce resistance gene activity.

## Contribution

The study provides new insights into how antibiotic combinations modulate resistance gene expression in MDR A. baumannii.

## Key findings

- Colistin–meropenem synergistically reduced blaADC and blaOXA-51 gene expression in all three strains.
- Sulbactam–colistin synergy was observed in only one strain and had no significant effect on gene expression.
- All combinations reduced adeB expression, but carO and omp33–36 varied by strain and antibiotic.

## Abstract

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.