Abstract
Infections with bacterial biofilm communities are highly tolerant of antibiotics. This protection is attributed, in part, to a hydrated extracellular polymeric substance (EPS) that surrounds the bacterial community and that limits antibiotic diffusion. In this study, we evaluated whether it is possible to dehydrate and then re-hydrate a biofilm as a means to increase antibiotic penetration and efficacy. Acinetobacter baumannii biofilms (24 h) were exposed to hypertonic concentrations of maltodextrin, sucrose or polyethylene glycol (PEG) as the dehydration step. These biofilms were then washed with deionized water containing 10 times the concentration of antibiotics needed to kill these bacteria in broth culture (50 µg/mL tobramycin, 300 µg/mL chloramphenicol, 20 µg/mL ciprofloxacin or 100 µg/mL erythromycin) as the rehydration step. Biofilms were then harvested, and the number of viable cells was determined. Sequential treatment with PEG and tobramycin reduced cell counts 4 to 7 log (p < 0.05) relative to combining PEG and tobramycin in a single treatment, and 3 to 7 log relative to tobramycin treatment alone (p < 0.05). Results were variable for other osmotic compounds and antibiotics depending on the concentrations used, likely related to mass and hydrophobicity. Our findings support future clinical evaluation of sequential regimens of hypertonic and hypotonic solutions to enhance antibiotic efficacy against chronic biofilm infections.
Highlights
Bacterial biofilm is composed of a bacterial community that is embedded in a self-produced matrix that is composed of carbohydrates, proteins and nucleic acids
Followed by tobramycin in water would enhance the efficacy of the antibiotic against A. baumannii biofilm by tobramycin in water with would enhance treatment the efficacy of theTreatment antibiotic of against
Biofilm tobramycin communities compared with antibiotic treatment alone
Summary
Bacterial biofilm is composed of a bacterial community that is embedded in a self-produced matrix that is composed of carbohydrates, proteins and nucleic acids (“extracellular polymeric substance,”or EPS). Once established on biotic and abiotic surfaces, biofilm communities are more resistant to antibiotics compared to planktonic cells. From a clinical perspective Acinetobacter baumannii is a biofilm-forming organism that poses serious challenges including with diabetic foot wounds [1,2,3,4,5]. The principal mechanism by which the hydrated EPS protects bacteria is via reduced diffusion [7,8], other mechanisms have been described [9,10]. These include antibiotic-modifying enzymes, electrostatic interactions, altered microenvironments and slow
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