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.

Salmonella typhimurium plasmids simultaneously coding for tetratcycline resistance, colicin production and pathogenicity

Duas linhagens selvagens de Salmonella typhimurium abrigando dois plasmídios de 100 e 90 kb foram isoladas de água-esgoto e material clínico. A partir de experimentos de conjugaçäo, cura, análise do conteúdo plasmidial através de eletroforese em gel de agarose e bioensaio com camundongos CFW observou-se que o plasmídio de 100 kb codifica simultaneamente resistência a 64µ/mL de tetraciclina, produçäo de colicina e patogenicidade, enquanto que o plasmídio de 90kb pode ser considerado como crítico, em ambas linhagens, nas condiçöes experimentais dessa pesquisa. O processo de cura dessas linhagens com SDS atingiu apenas o plasmídio de peso molecular mais elevado, quando as linhagens bacterianas perderam simultaneamente, as 3 características. Ao realizar os ensaios de conjugaçäo com E.coli K12 e S.typhimurium, as transconjugantes receberam ambos ou apenas o plasmídio de 100 Kb e, associado a este, as propriedades de resistência à tertraciclina, produçäo de colicina e patogenicidade. É a primeira vez que se descrevem essas 3 propriedades codificadas simultaneamente pelo mesmo plasmídio em S.typhimurium

Multidrug resistant typhoid fever: therapeutic considerations.

Forty six blood culture positive cases were studied during the current outbreak of multidrug resistant typhoid fever (MRTF). The present outbreak was caused by E1 phage type and organisms were resistant to all commonly used drugs for the treatment of typhoid fever, viz., chloramphenicol (78%), co-trimoxazole (76%) and ampicillin (68%). Treatment failures with chloramphenicol (45.5%) corroborated well with in vitro resistance. No treatment failure was seen with chloramphenicol and ceftriaxone, when these drugs were used in cases infected with sensitive strains. Among the alternative drugs used in cases with in vitro sensitivity, successful clinical response was seen with ceftriaxone (4/4) and cefotaxime (8/9) as compared to cephalexin (3/5) or a combination of cephalexin and furazolidone (9/12).