Tetracyclines

Tetracyclines 화학적 특성, 용도, 생산

• Antimicrobial activity

  Tetracyclines are broad-spectrum, essentially bacteristatic agents. They share a similar spectrum of activity, though that of tigecycline is somewhat different from that of earlier tetracyclines.
  In general, tetracyclines are active against many Gram-positive and Gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, coxiellae, spirochetes and some mycobacteria. Most streptococci are sensitive, except Streptococcus agalactiae, and enterococci. Susceptible Gram-positive bacilli include Actinomyces israelii, Arachnia propionica, Listeria monocytogenes, most clostridia and Bacillus anthracis. Nocardia spp. are much less susceptible, minocycline demonstrating the greatest activity against them.
  Among Gram-negative bacteria most enterobacteria and most strains of Moraxella catarrhalis, Neisseria meningitidis and Haemophilus influenzae are sensitive. Legionellae, brucellae, Francisella tularensis, Vibrio cholerae, Campylobacter spp., Helicobacter pylori, Plesiomonas shigelloides and Aeromonas hydrophila are all susceptible. Many anaerobic bacteria are susceptible, doxycycline and minocycline being the most active. Rickettsiae are generally sensitive, especially to doxycycline, minocycline and tetracycline. None is active against Pseudomonas aeruginosa, Proteus spp. or Providencia spp., but Burkholderia pseudomallei and Stenotrophomonas maltophilia are usually susceptible.

• 원료

  Resistance to tetracyclines has emerged in an ever-increasing number of bacterial species and is geographically widespread. Resistance arises primarily from acquisition of genes that either encode transporters of the major facilitator superfamily (MFS), which remove the antibiotics from the cell (e.g. TetB, TetK), or encode proteins that protect the ribosome from inhibition (e.g. TetM, TetO). Tigecycline is not affected by these resistance mechanisms and consequently is active against many species resistant to earlier tetracyclines. In some Gram-negative bacteria resistance can also be due to the activity of innate (endogenous) bacterial efflux proteins such as the chromosomally encoded resistance–nodulation– cell division efflux pumps that confer resistance to several structurally unrelated biocides and antibiotics, as well as all classes of tetracyclines. The presence of these pumps explains the inherent resistance of most Ps. aeruginosa and Proteus spp. to all tetracyclines.

• Pharmaceutical Applications

  A group of natural products derived from Streptomyces spp. and their semisynthetic derivatives. The minimum pharmacophore is a linear fused tetracyclic molecule, 6-deoxy-6-demethyltetracycline.
  The various members of the class contain a variety of functional groups attached to the rings designated A, B, C and D. Natural products include chlortetracycline, oxytetracycline, tetracycline and demeclocycline (demethychlortetracycline). Semisynthetic derivatives include doxycycline, minocycline, methacycline, lymecycline, rolitetracycline and tigecycline, a glycylcycline that has been specifically developed to overcome problems of bacterial resistance to earlier tetracyclines.

• Clinical Use

  The use of tetracyclines has significantly declined in most countries as the incidence of bacterial resistance has increased and more active and better tolerated antimicrobial agents have been introduced. However, some new applications have emerged, such as their use as part of multidrug regimens for the management of gastritis and peptic ulcer disease associated with H. pylori. Their activity against malaria has become important for prophylaxis following the rapid increase of chloroquine- and mefloquine-resistant Plasmodium falciparum.
  Tigecycline is currently approved only for use in complicated skin and skin structure infections (including those caused by methicillin-resistant Staph. aureus), complicated intra-abdominal infections and community- acquired bacterial pneumonia, but use for other indications, may emerge if there is suitable clinical evidence.