Antibiotic functionalised polymers reduce bacterial biofilm and bioburden in a simulated infection of the cornea

Abstract

Microbial keratitis can arise from penetrating injuries to the cornea. Corneal trauma promotes bacterial attachment and biofilm growth, which decrease the effectiveness of antimicrobials against microbial keratitis. Improved therapeutic efficacy can be achieved by reducing microbial burden prior to antimicrobial therapy. This paper assesses a highly-branched poly(N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van), for reducing bacterial attachment and biofilm formation. The polymer lacked antimicrobial activity against Staphylococcus aureus, but significantly inhibited biofilm formation (p = 0.0008) on plastic. Furthermore, pre-incubation of S. aureus cells with HB-PNIPAM-van reduced cell attachment by 50% and application of HB-PNIPAM-van to infected ex vivo rabbit corneas caused a 1-log reduction in bacterial recovery, compared to controls (p = 0.002). In conclusion, HB-PNIPAM-van may be a useful adjunct to antimicrobial therapy in the treatment of corneal infections.

Silver Nanoparticles from Oregano Leaves’ Extracts as Antimicrobial Components for Non-Infected Hydrogel Contact Lenses

“…The necessity of the surgical removal of the infected tissue, which is then followed in the untreated cases, contains high risk for corneal blindness. The biofilm elimination can be achieved by applying metallodrugs [22].…”

Dual bioresponsive antibiotic and quorum sensing inhibitor combination nanoparticles for treatment of Pseudomonas aeruginosa biofilms in vitro and ex vivo

“…9 Novel therapeutic strategies are thus urgently needed to combat the threat of biofilm-centred infections. [10][11][12][13][14][15][16][17] One of the most promising approaches is the combined-use of antibiotics with adjuvants that do not affect the pathways essential for the bacterial growth and viability, and as a consequence are less likely to select for resistance. Such agents have various modes of action including (i) increasing bacterial cell membrane permeability, (ii) impairing biofilm formation, and/ or the production of virulence factors and antibiotic resistance elements, (iii) blocking antibiotic efflux pumps and (iv) changing phenotype from the biofilm to the planktonic state through biofilm dispersal.…”

Corneal Infection Models: Tools to Investigate the Role of Biofilms in Bacterial Keratitis

“…To the best of our knowledge, an in vitro model that combines live HCE cells and the formation of bacterial biofilm is yet to be reported. In contrast, multiple keratitis studies have investigated biofilm formation on abiotic surfaces in the absence of cells [131,132]. As in vitro modelling techniques continue to improve, co-culture models may be reported but there are various limitations associated with the use of in vitro systems for studying biofilm infections [133].…”

“…Despite issues with standardisation, ex vivo models have been used to study various aspects of bacterial keratitis. This includes: epithelial barrier function [137,169], effect of bacteria on epithelial cell migration [150], bacterial transmission from contact lenses [145,149,170], bacterial adherence to corneal epithelium [168], movement of bacteria in stroma [146], role of virulence factors [139,147] and drug testing of new ophthalmic antimicrobials [132,148]. Despite the popularity of ex vivo corneal infection models, biofilm formation under these conditions remains to be characterised.…”