Vitamin C in the Presence of Sub-Inhibitory Concentration of Aminoglycosides and Fluoroquinolones Alters Proteus mirabilis Biofilm Inhibitory Rate.

Joanna Kwiecińska-Piróg,Agata Białucha,Krzysztof Skowron,Jana Przekwas,Eugenia Gospodarek-Komkowska,Tomasz Bogiel

doi:10.3390/antibiotics8030116

Abstract

Vitamin C has antimicrobial activity and is often used as an oral supplement accompanying antibiotic treatment in urinary tract infections (UTI). Proteus mirabilis is the third common species responsible for UTIs that are mostly treated with fluoroquinolones or aminoglycosides. Treatment of the UTI caused by P. mirabilis is problematic due to the ability to form biofilm on the urinary catheters. The aim of the study was to evaluate the influence of ascorbic acid in combination with antibiotics on P. mirabilis abilities to form biofilm. The susceptibility of P. mirabilis reference strain ATCC® 29906™ and four clinical strains isolated from the urine samples of patients with urinary catheter were evaluated according to EUCAST recommendations. The influence of ascorbic acid (0.4 mg × mL−1) in combination with antibiotics on biofilm formation was evaluated spectrophotometrically. Aminoglycosides at sub-inhibitory concentrations more successfully limited biofilm formation by P. mirabilis strains without ascorbic acid addition. Inhibition rate differences at the lowest concentrations of gentamicin and amikacin were statistically significant (p ≤ 0.05). Ascorbic acid addition to the culture medium limited the inhibitory effect of fluoroquinolones, facilitating biofilm formation by P. mirabilis strains. The addition of ascorbic acid during aminoglycosides therapy may disturb treatment of urinary tract infections related to the presence of P. mirabilis biofilm.

Highlights

IntroductionVitamin C (ascorbic acid, AA) was first identified in the 1920s by a Hungarian biochemist, Albert
Vitamin C was first identified in the 1920s by a Hungarian biochemist, AlbertSzent-Györgyi [1]
Biofilm constitution limits antimicrobial penetration and distribution through the whole structure, mostly to the bacteria submerged in its deeper layers, generating sub-inhibitory antibiotics concentrations

Summary

Introduction

Vitamin C (ascorbic acid, AA) was first identified in the 1920s by a Hungarian biochemist, Albert. This vitamin cannot be synthesized by humans, dietary supplementation of about 75–1000 mg per day is needed [1]. Ascorbic acid (after oral intake) is absorbed from the small intestine and transported into cells by specific transporters: Sodium-depend Vitamin C Transporters (SVCTs)-1 or -2. The concentration of AA in human tissues (200–2300 μM, depending on the organ) is much higher than in body fluids (i.e., 50–70 μM in plasma) and depends strongly on dietary intake of vitamin C [2]. Intake of AA impacts on its bioavailability—it is very high if AA is supplemented in small doses (15–30 mg/day) and decreases if high doses are provided [2]. Higher doses (>100 mg/day) increase plasma AA concentration, and are almost totally excreted in the urine [3]

Objectives

Methods

Conclusion