Tetracyclines Chemische Eigenschaften,Einsatz,Produktion Methoden
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.
Acquired resistance
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.
Pharmazeutische Anwendungen
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.
Tetracyclines Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
