In-vitro model for bacterial growth inhibition of compartmentalized infection treated by an ultra-high concentration of antibiotics

This original research work is aimed at demonstrating the efficacy of the novel continuous in-situ targeted, ultra-high concentration antibiotic (CITA) treatment for localized infections while avoiding systemic toxicity.

For the first time the laser light scattering technology was applied to analyze the activity of high concentration of antibiotic in an in-vitro model of infection.

Bacteria such as Pseudomonas aeruginosa, E. coli and Staphylococcus aureus are the main pathogens in infected cardiovascular-implantable

electronic device and are associated with high morbidity and severe complications.

Systemic antibiotic treatments, both oral and intravenous, are often not sufficient to resolve infections, especially in cases of biofilm production that induces antibiotic resistance and difficulties in eradication, which would require drug treatment at such high concentrations to result toxic.

Local and continuous administration of high antibiotic concentration enhance the accumulation into soft tissues, thus eradicating biofilm and preventing re-colonization.

As the range in commercially available AST tests corresponds to 1 MIC per type of isolated strain, they are not applicable for ultra-high dosage as 10E2-10E3 MIC. In this study, thanks to the HB&L culture system and broth in vials, it was possible to prepare high antibiotics concentrations (10E3MIC) from the different drug molecules (gentamicin, amikacin and vancomycin), and monitor their activity in an in-vitro conceptualized model of heavy bacterial infections (10E6 CFU/ml) by growth curves analysis with incubation times of up to 72 hours.

The results of the present study provide a proof-of-concept for the application of CITA as a novel approach for the antibiotic treatment of localized bacterial infections.

Though not the main objective of this experiment, the results of this study indicate that the H&BL system allows the rapid determination of ineffective empirical antibiotic treatment regardless of the identification of the drug-resistant pathogen causing the infection.

Therefore, an early adjustment of an appropriate antibiotic treatment can be achieved even before pathogen identification and susceptibility.

The latency time of the exponential growth phase can serve as an early and effective indicator of the susceptibility of infectious bacteria to a specific antibiotic.