Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria residing in a complex biofilm within a susceptible host. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate. Our study aimed to evaluate the efficacy of amixicile, when compared to metronidazole, in inhibiting the growth of bacteria present in a microbiome harvested from patients with chronic periodontitis. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour growth the bacterial DNA was analyzed using quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), and S.sanguis (Ss). Both drug treatment groups yielded a statistical significant reduction for several anaerobic bacteria: Pi (P