USAGE OF SILVER NANOPARTICLES TO RESTORE MOXIFLOXACIN EFFICACY FOR FLUOROQUINOLONE-RESISTANT M. TUBERCULOSIS CULTURES.

Abstract

Background: Fluoroquinolones are used for the complex treatment of mono-, poly-, and multi-resistant Tuberculosis (TB) and are the most efficient among resistant TB treatment drugs. Disease caused by fluoroquinolone-resistant TB strains, especially pre-extensive TB (pre-XDR) and extensive (XDR) forms are extremely hard to manage, and treatment efficacy is quite low. With the revitalization and extension of resistant TB drugs, one of the main research domains is to study resistance inhibitors aimed at restoring the efficacy of main and priority anti-TB medications. The antibacterial properties of silver nanoparticles (AgNPs) against resistant strains responsible for various infectious diseases are supported by extensive experimental data. There are a few publications regarding the effectiveness of silver nanoparticles on resistance inhibition of TB strains, however, its action on fluoroquinolone-resistant TB strains is unexplored.

Aim: The study aimed to investigate the in vitro restoration of the anti-TB efficacy of Moxifloxacin (Mfx) using AgNPs.

Methods: Nanocomposite- standard dose of Mfx and 20 nm silver nanoparticles (AgNPs) suspension solution of 6 different concentrations: 0.25%; 0.5%; 1%; 2.5%; 5% and 10%, were supplemented to 70 moxifloxacin-resistant mycobacterium tuberculosis isolates. The control arm consisted of 70 fluoroquinolone (Mfx)-resistant Mycobacterium tuberculosis (FQ/ R-MTB) isolates and AgNPs suspension with identical concentrations. The inhibitory effect of nanocomposites was evaluated by MTB growth rate using the BACTECTM MGIT 960TM.

Results: The suppression process of AgNPs on FQ/R-MTB isolates started with 2,5% nanocomposite solution application and full suppression was achieved in 5% and 10% nanocomposite solutions. A standard dose of Mfx and a 2.5% solution of AgNPs increased the minimal inhibitory effect on FQ/R-MTB by 10% (total 85%) vs the isolated use of a 2.5% solution of AgNPs (75%). A similar trend was noted in both FQ/R-MTB cohorts (rifampicin-susceptible; rifampicin-resistant).

Conclusion: The in vitro study of the effectiveness of using AgNPs and Mfx nanocomposite on FQ/R-MTB isolates proves the potentiating effect of AgNPs at a standard dose of Mfx, overcoming the drug resistance of the pathogen, which lays the groundwork for further scientific research in this area and creating a nanocomposite that is safe for humans, which will make a significant contribution to improving the control of fluoroquinolone-resistant tuberculosis, especially, pre-XDR TB.