Antimicrobial photodynamic effect of the photosensitizer riboflavin, alone and in combination with colistin, against pandrug-resistant Pseudomonas aeruginosa clinical isolates

Ehsan Najari; Samin Zamani; Mehdi Sheikh Arabi; Abdollah Ardebili

doi:10.1016/j.jiac.2024.03.001

Antimicrobial photodynamic effect of the photosensitizer riboflavin, alone and in combination with colistin, against pandrug-resistant Pseudomonas aeruginosa clinical isolates

J Infect Chemother. 2024 Mar 2:S1341-321X(24)00075-8. doi: 10.1016/j.jiac.2024.03.001. Online ahead of print.

Authors

Ehsan Najari¹, Samin Zamani², Mehdi Sheikh Arabi³, Abdollah Ardebili⁴

Affiliations

¹ Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: e_najari@yahoo.com.
² Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: samin.zamanii@gmail.com.
³ Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: msheykharabi@yahoo.com.
⁴ Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: aardebili2014@gmail.com.

PMID: 38432556
DOI: 10.1016/j.jiac.2024.03.001

Abstract

Introduction: Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates.

Methods: Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration.

Results: Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log₁₀ CFU/mL and 0.43 log₁₀ CFU/mL reductions in PA1, and 0.28 log₁₀ CFU/mL and 0.34 log₁₀ CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41-0.7 log₁₀ CFU/mL reduction for PA1 and 0.35-0.83 log₁₀ CFU/mL reduction for PA2 (P = 0.001).

Conclusions: This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections.

Keywords: Antimicrobial photodynamic therapy; Antimicrobial resistance; Colistin; Light-emitting diode; Pseudomonas aeruginosa; Riboflavin.

Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.