Exploration of the Pharmacodynamics for Pseudomonas aeruginosa Biofilm Eradication by Tobramycin

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen which is involved in numerous infections. It is of growing concern within the field of antibiotic resistance and tolerance and often exhibits multidrug resistance. Previous studies have shown the emergence of antibiotic-resistant and -tolerant variants within the zone of clearance of a biofilm lawn after exposure to aminoglycosides. As concerning as the tolerant variant emergence is, there was also a zone of killing (ZOK) immediately surrounding the antibiotic source from which no detectable bacteria emerged or were cultured. In this study, the ZOK was analyzed using both in vitro and in silico methods to determine if there was a consistent antibiotic concentration versus time constraint (area under the curve [AUC]) which is able to completely kill all bacteria in the lawn biofilms in our in vitro model. Our studies revealed that by achieving an average AUC of 4,372.5 mu g.h/mL, complete eradication of biofilms grown on both agar and hydroxyapatite was possible. These findings show that appropriate antibiotic concentrations and treatment duration may be able to treat antibiotic-resistant and -tolerant biofilm infections.