EFFECT OF ANTIBIOTICS ON ORAL BIOFILMS IN VIVO

Forsyth Institute, Cambridge MA

Investigators

Linked publications & trials

Abstract

Biofilms found on mammalian tissue surfaces contain complex mixtures of bacterial species growing within a glycocalyx matrix. Species in biofilms have shown remarkably greater resistance to antibiotics than when grown in a planktonic state. Surprisingly little is known about the effect of systemically administered antibiotics on the microbial composition of naturally occurring, complex biofilms. Thus, the long-term objective of this proposal is to determine the effect of antibiotics on the microbial composition of biofilms as they exist in vivo and to determine if the proportion and nature of antibiotic resistant taxa is affected. Subgingival biofilms that occur on teeth will be employed as a model system because of their complexity, ready accessibility and known microbial composition. Specific Aim 1 will examine the effects of 3 systemically administered antibiotics on the microbial composition of subgingival biofilms in adult humans with periodontitis. All subjects will receive scaling and root planing and will be randomly assigned to one of 4 groups of 36 subjects each receiving one of doxycycline, amoxicillin, metronidazole or control. 28 subgingival biofilm samples will be taken in each subject at baseline, at selected time points while the agent is being taken, the same time points after cessation of the agent as well as at 3, 6 and 12 months. These samples will be evaluated individually for their content of 40 subgingival species using checkerboard DNA-DNA hybridization. Data will be evaluated longitudinally and compared with clinical parameters. Specific Aim 2 will examine the proportion and nature of subgingival species that are resistant to 4 mug/ml of the test antibiotic at the same time points. Subgingival biofilm samples will be plated on media with and without the test antibiotic and resistant isolates identified using DNA probes. Data from this investigation will indicate the kinetics of suppression of species in subgingival biofilms during antibiotic administration, the kinetics of repopulation after antibiotic withdrawal as well as the nature and proportion of subgingival species that are resistant to the antibiotics at different time points. The data should indicate the effects of antibiotics on the microbial composition of complex ecosystems such as those found in biofilms and be useful in guiding and interpreting in vitro studies of mechanisms of antibiotic resistance.