Experimental treatment of endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa infection with nanoparticle-based conjugates.

Abstract

Relevance. Pseudomonas aeruginosa (PA) is an extremely dangerous microorganism whose elimination from the host organism is very difficult due to the presence of multidrug resistance (MDR) factors in PA. The outcome of endophthalmitis (EP) mediated by PA in 50% of cases will be evisceration of the eyeball, and more than 95% of patients receive visual acuity – hand movements near the face and below. In this regard, studies of quantum dots (QDs), which have shown high anti-infective activity in laboratory conditions, are of particular relevance. Purpose. Evaluation of the effectiveness of the treatment of EP caused by PA with MDR using QDs-based conjugates in the experiment. Material and methods. The object of the study was laboratory rabbits of the Chinchilla breed (n=27), male, aged from 3 to 3.5 months. As an EP inducer, all laboratory animals underwent intravitreal injection (IVI) of a multidrug-resistant PA strain in a volume of 0.05 ml in the right eye. QDs of the Ag (10%):InP/ZnS MPA type were taken as the basis for the creation of conjugates with antibiotics (AB). After the manifestation of EP, the animals underwent intravitreal injections (IVI) of dosage forms in accordance with the distribution into the following subgroups, 3 rabbits in each. Subgroups No. 1–3 – IVI 2.25 mg/0.1 ml Ceftazidime. Subgroups No. 4–6 – IVI 0.1 ml of QDs solution at concentrations of 10%, 0.1%, 0.01%, respectively. Subgroups No. 7–9 – IVI solution of QDs 0.05 ml (at concentrations of 10%, 0.1%, 0.01%, respectively) in combination with 2.25 mg/0.05 ml of Ceftazidime (conjugates). Efficacy was evaluated based on clinical parameters: the dynamics of hypopyon resorption, the presence of inflammatory cells in the anterior chamber, the dynamics of regression of pathological suspension in the vitreal cavity, the dynamics of pathological neovascularization of the iris, the dynamics of the cornea. Results. Rabbits from subgroups No. 1–3 (1st group) were characterized by the least dynamics in relation to the regression of symptoms during the 7-day observation period. Rabbits from subgroups No. 4–6 (2nd group) were characterized by moderate positive dynamics in relation to the regression of symptoms. Rabbits from subgroups No. 7–9 (3rd group) were characterized by the best positive dynamics in relation to the regression of symptoms. Conclusion. It was possible to prove the effectiveness of the treatment of experimental antibiotic-resistant EP caused by a strain of PA with MDR by means of QDs Ag(10%):InP/ZnS MPA at concentrations of 10%, 0.1% and 0.01%, especially in combination with 2.25 mg/0.05 ml of Ceftazidime in as a conjugate. Based on the results obtained, it can be assumed that active research and the use of QDs as conjugates with modern ABs can solve the overall problem of combating MDR strains. Key words: Pseudomonas Aeruginosa, quantum dots, endophthalmitis, multidrug resistance, antibiotic resistance, conjugates