Synergistic combination of imipenem and 7-fluoroindole inhibits β-lactamases and biofilm in Carbapenem-resistant Acinetobacter baumannii.

Background: Acinetobacter baumannii is a nosocomial opportunistic pathogen responsible for hospital and community-acquired infections. It has been categorised as a high-priority ESKAPE pathogen due to escalating resistance, underscoring the urgent need for effective treatment options. This study explores the use of 7-Fluoroindole (7-FI) as an adjuvant to imipenem for combating Carbapenem-Resistant Acinetobacter baumannii (CRAB).

Methods: Clinical strains of A. baumannii were subjected to disc diffusion assay for antibiotic resistance profile, and Fractional Inhibitory Concentration (FIC) of 7-FI was determined with imipenem by checkerboard assay. Expression of β-lactamases, efflux pumps, and outer membrane proteins was determined by qRT-PCR. Biofilm inhibition by 7-FI in combination with imipenem was evaluated by Confocal Laser Scanning Microscopy.

Results: 7-FI reduced the MIC of imipenem by 2 to 8-fold in CRAB strains, and also enhanced susceptibility to meropenem. Mechanistically, 7-FI inhibited the β-lactamase activity by 2.3 to 3.8-fold and downregulated the expression of Class B (blaNDM-1) and D (blaOXA-23 and blaOXA-51) β-lactamases. The efflux pump activity was reduced by 2 to 8.6-fold, and expression of efflux pump genes adeB, adeJ, abeM and emrA was also significantly (p < 0.001) downregulated. 7-FI in combination with imipenem inhibited biofilm formation by 80% even at 1 × FIC (1/4 MIC of imipenem and 1/3 MIC of 7-FI).

Conclusion: The combination of 7-FI and imipenem synergistically mitigated carbapenem resistance in A. baumannii by inhibiting the activity of β-lactamases, downregulating the expression of β-lactamases and efflux pumps. The study shows 7-FI as a useful adjuvant to imipenem against CRAB strains.