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

Abstract

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.

Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen

“…As little is known about mechanisms of antibiotic resistance in A. actinomycetemcomitans, we next decided to use the ordered library to screen for genes involved in erythromycin resistance. Macrolides, such as erythromycin, inhibit formation of the 50S ribosomal subunit (26) and represent one of the most commonly used classes of antibiotics for treating periodontal disease (24). To perform this screen, we first determined that the MIC of erythromycin for A. actinomycetemcomitans is 2 g/ml, which falls within previously reported ranges (27).…”

“…Though periodontitis is treatable by eliminating plaque physically, many cases of periodontitis are highly refractory and necessitate chemical treatment with antibiotics (22,23). However, antibiotic resistance among periodontal pathogens is widespread (24), motivating a search for alternative therapies and a better understanding of bacterial resistance mechanisms.…”

Investigations on the genomic diversity of OXA from isolated Acinetobacter baumannii

“…Typically, isolates of A. baumannii usually present multidrug resistance, including resistance to third generation cephalosporins, aminoglycosides, and fluoroquinolone (Sinha and Srinivasa, 2007). Previous experimental study has reported that the most common mechanism of drug resistance is the presence of hydrolyzing β-lactamases, including metallo-β-lactamases (Ambler class B) and oxacillinases (Ambler class D) (Soares et al, 2012). The widespread use of antimicrobial chemotherapy has played an important role in the appearance of carbapenem-hydrolyzing class D β-lactamases (CHDLs), which have been widely identified in A. baumannii.…”

Effects of Japanese traditional herbal medicines (Kampo) on growth and virulence properties ofPorphyromonas gingivalisand viability of oral epithelial cells

“…However, the use of pharmaceutical antibiotics is associated with a raise in resistant bacterial strains, although this aspect has been poorly studied in dentistry (Soares et al, 2012). Natural phytochemicals may be effective in overcoming this problem as well as minimizing adverse effects of some antibiotics (Palombo, 2011).…”