Combination of isothiocyanates and antibiotics increases susceptibility against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens

Bidii Stephen Ngalah; Katharina Börner; Moritz Kropidlowsky; Johanna Finkbeiner; Alexander Harter; Klaus Biehler; Uwe Frank

doi:10.1016/j.fitote.2022.105382

Combination of isothiocyanates and antibiotics increases susceptibility against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens

Fitoterapia. 2022 Nov 30:105382. doi: 10.1016/j.fitote.2022.105382. Online ahead of print.

Authors

Bidii Stephen Ngalah¹, Katharina Börner², Moritz Kropidlowsky², Johanna Finkbeiner², Alexander Harter², Klaus Biehler², Uwe Frank³

Affiliations

¹ BioPhytoMedical Drug Discovery and Development, Freiburg im Breisgau, Germany; Medical Faculty, University of Heidelberg, Heidelberg, Germany.
² BioPhytoMedical Drug Discovery and Development, Freiburg im Breisgau, Germany.
³ BioPhytoMedical Drug Discovery and Development, Freiburg im Breisgau, Germany. Electronic address: biophyto@gmx.com.

PMID: 36462662
DOI: 10.1016/j.fitote.2022.105382

Abstract

Background: The development and spread of multidrug-resistant organisms (MDRO) is evolving rapidly worldwide. Although effective antibiotics are still available, some infections are difficult to treat. Among MDROs, S. marcescens and A. baumannii are among the difficult-to-treat pathogens causing for instance sepsis and urinary tract infections (UTI). Isothiocyanates (ITC) are natural plant products. The antimicrobial properties of ITC appear to be more effective in combination with some antibiotics.

Purpose: We investigated a mixture of ITC from nature-identical plant extracts of nasturtium and horseradish in different combined concentrations with broad-spectrum antibiotics against S. marcescens, A. baumannii, E. coli, K. pneumoniae and P. mirabilis.

Methods: First, we investigated the antibacterial activity of the compounds by standard agar disc diffusion test. Next, we evaluated the minimum inhibitory concentrations (MIC) via broth dilution tests. Checkerboard technique was used to assess antimicrobial effects against sulfamethoxazole-trimethoprim, ampicillin-sulbactam, nitrofurantoin, Fosfomycin, ciprofloxacin and imipenem combined with various concentrations of ITC.

Results: S. marcescens strains 1-3 showed reversal of resistance at >0.075 μg/mL ITC in combination with nitrofurantoin, whereas 0.05 μg/mL ITC increased antimicrobial susceptibility. Combination of fosfomycin with 0.003 μg/mL ITC resulted in increased efficacy against resistant S. marcescens strains, E. coli, K. pneumoniae and P. mirabilis. Remarkable additive antimicrobial activity was observed at 0.03 μg/mL and 0.06 μg/mL ITC in combination with 0.125 μg/mL imipenem (FIC > 0.5).

Conclusion: The combination of ITC and antibiotics is a promising approach for the treatment of UTI caused by MDRO. The ITC combination with selected antibiotics had synergistic and additive effects.

Keywords: A. baumannii; Antimicrobial activity; Fractional inhibitory concentration index (FIC); Isothiocyanates; K. pneumoniae; P. mirabilis; S. marcescens.