Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

In Vitro Resensitization of Fluoroquinolones and Carbapenems Against Biofilm-Forming and Multidrug-Resistant Salmonella and Shigella spp. Using Riboflavin

Version 1 : Received: 15 March 2024 / Approved: 15 March 2024 / Online: 15 March 2024 (15:02:25 CET)

How to cite: Abban, M.K.; Mensa, M.; Gayi, B.; Addo, G.K.; Ofori, M.E.O.; Ayerakwa, E.A.; Isawumi, A. In Vitro Resensitization of Fluoroquinolones and Carbapenems Against Biofilm-Forming and Multidrug-Resistant Salmonella and Shigella spp. Using Riboflavin. Preprints 2024, 2024030934. https://doi.org/10.20944/preprints202403.0934.v1 Abban, M.K.; Mensa, M.; Gayi, B.; Addo, G.K.; Ofori, M.E.O.; Ayerakwa, E.A.; Isawumi, A. In Vitro Resensitization of Fluoroquinolones and Carbapenems Against Biofilm-Forming and Multidrug-Resistant Salmonella and Shigella spp. Using Riboflavin. Preprints 2024, 2024030934. https://doi.org/10.20944/preprints202403.0934.v1

Abstract

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited >80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

Keywords

riboflavin; biofilms; vitamin B2; carbapenems; fractional inhibitory concentration; 3D chequerboard

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

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