Efficacy of InP/ZnSe/ZnS quantum dots with antibiotics in the treatment of multidrug-resistant Pseudomonas aeruginosa keratitis: Preclinical studies.

Abstract

Antibiotic resistance and the development of fundamentally new drugs and approaches for the conservative treatment of bacterial keratitis are among the main challenges of modern ophthalmology. Laboratory and clinical-experimental studies to model and treat infectious keratitis caused by a hospital strain of Pseudomonas aeruginosa (P. aeruginosa) with multiple drug resistance in laboratory animals using colloidal quantum dots (QD) based conjugates with an InP/ZnSe/ZnS core/multilayer shell structure and antibiotics (tobramycin, cefotaxime) were performed. Experimental randomized animal study with 30 New Zealand White laboratory rabbits was conducted. During the modeling and treatment of infectious keratitis, clinical monitoring of laboratory animals was performed, including the assessment of symptom regression over time, photoregistration of the anterior segment with fluorescein staining, and optical coherence tomography. The susceptibility of P. aeruginosa bacteria to antibiotics, and QD conjugates with cefotaxime was assessed in vitro using the disk diffusion method. The penetration of QD into the corneal layers of 18 enucleated pig eyes was studied using fluorescence microscopy. The high anti-infective activity of QD conjugates with antibiotics against an antibiotic-resistant hospital strain of P. aeruginosa was established both in vitro and in vivo. P. aeruginosa bacteria are resistant to cefotaxime in vitro but are susceptible to the QD solutions used in conjugates with an antibiotic. QD conjugates with tobramycin increase the effectiveness of keratitis treatment from 32 ± 2 % to 88 ± 3 % and accelerate the symptom reversal rate compared to standard antibacterial therapy with tobramycin.