Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

Antibiotics are important adjuncts in the treatment of infectious diseases,including periodontitis. the most severe criticisms to the indiscriminate use of these drugs are their side effects and,especially,the development of bacterial resistance. the knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. therefore,the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin,tetracycline,macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. antimicrobial resistance can be classified into three groups: intrinsic,mutational and acquired. penicillin,tetracycline and erythromycin are broad-spectrum drugs,effective against gram-positive and gram-negative microorganisms. bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins,or production of β-lactamases. however,a very small proportion of the subgingival microbiota is resistant to penicillins. bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell,by altering the ribosome in order to prevent effective binding of the drug,or by producing tetracycline/macrolide-inactivating enzymes. periodontal pathogens may become resistant to these drugs. finally,metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. acquired resistance to this drug has rarely been reported. due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species,metronidazole is a promising drug for treating periodontal infections.