Abstract
Purpose :
Infectious keratitis (IK) is the leading cause of corneal blindness. Its treatment presents a challenge given the rapid clearance of drugs through drainage of the tear film, the emergence of antimicrobial resistance and the need for rapid eradication of infection before permanent corneal damage occurs. We used mathematical modelling to explain and predict the synergistic effects of antibiotic and host defence peptide (HDP) combination therapy in bacterial keratitis.
Methods :
An ordinary differential equation (ODE) model was formulated to describe the evolving bacterial population, and antibiotic and HDP concentrations over time. Our equations account for bacterial division, the bactericidal effects of antibiotic and HDP, tear drainage and the development of resistance. The model was parameterised using data from the literature and through fitting to data from a previous experimental study, which used amikacin (an antibiotic) and CaD23 (a synthetic HDP) against a laboratory-strain S. aureus (SH1000), both individually and in combination. The full model was solved computationally, while reduced models were solved analytically (algebraically).
Results :
Our model demonstrated that amikacin and CaD23 act synergistically, their combined effect against SH1000 being greater than the sum of their individual effects. Further, simulations predict clinically-realistic treatment regimens to expedite the eradication of bacterial infections, while reducing the risk of dose-dependent toxicity.
Conclusions :
Antibiotic-HDP combination therapies present a promising route for treating bacterial IK, especially in light of their synergistic interaction. Further, our model provides a relatively quick and cost-effective means of trialling IK treatment regimens. In future work, we will expand our study to consider a range of antibiotics, HDPs and bacterial species.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.