Predictive modelling of a novel anti-adhesion therapy to combat bacterial colonisation of burn wounds

TL;DR

This paper develops a mathematical model to evaluate anti-adhesion therapy for bacterial burn wound infections, predicting its efficacy alone and combined with debridement, to improve treatment strategies against resistant bacteria.

Contribution

The study introduces a novel ODE-based model for anti-adhesion therapy, validated with in vivo data, and explores optimal treatment combinations for bacterial infection control.

Findings

Anti-adhesion therapy reduces bacterial burden by preventing adhesion and decreasing bacterial flux.

Combination of anti-adhesion therapy with debridement can potentially eliminate bacteria.

Model suggests anti-adhesion therapy alone cannot fully eradicate infection.

Abstract

As the development of new classes of antibiotics slows, bacterial resistance to existing antibiotics is becoming an increasing problem. A potential solution is to develop treatment strategies with an alternative mode of action. We consider one such strategy: anti-adhesion therapy. Whereas antibiotics act directly upon bacteria, either killing them or inhibiting their growth, anti-adhesion therapy impedes the binding of bacteria to host cells. This prevents bacteria from deploying their arsenal of virulence mechanisms, while simultaneously rendering them more susceptible to natural and artificial clearance. In this paper, we consider a particular form of anti-adhesion therapy, involving biomimetic multivalent adhesion molecule (MAM) 7 coupled polystyrene microbeads, which competitively inhibit the binding of bacteria to host cells. We develop a mathematical model, formulated as a system of ordinary differential equations, to describe inhibitor treatment of a Pseudomonas aeruginosa burn wound infection in the rat. Benchmarking our model against in vivo data from an ongoing experimental programme, we use the model to explain bacteria population dynamics and to predict the efficacy of a range of treatment strategies, with the aim of improving treatment outcome. The model consists of two physical compartments: the epithelium and the exudate. It is found that, when effective in reducing the bacterial burden, inhibitor treatment operates both by preventing bacteria from binding to the epithelium and by reducing the flux of daughter cells from the epithelium into the exudate. Our model predicts that inhibitor treatment cannot eliminate the bacterial burden when used in isolation; however, when combined with regular or continuous debridement of the exudate, elimination is theoretically possible. Lastly, we present ways to improve therapeutic efficacy, as predicted by our mathematical model.