GLYCOPEPTIDES:
VANCOMYCIN AND TEICOPLANIN
Vancomycin (Vancocin) is a complex tricyclic
glycopep-tide antibiotic produced by Streptomyces
orientalis, while teicoplanin (Targocid)
is derived from Actino-planes (Actinomyces) teichomyceticus. Teicoplanin has two major components: a phosphoglycolipid (A1) and five
chlorine-containing glycopeptides (A2). It is avail-able as an
investigational drug.
The glycopeptides are inhibitors of cell wall synthesis. They bind to the terminal
carboxyl group on the D-alanyl-D-alanine terminus of the N-acetylglucosamine-N-acetylmuramic acid peptide and prevent polymeriza-tion of the linear
peptidoglycan by peptidoglycan synthase.
They are bactericidal in vitro.
The glycopeptides are
narrow-spectrum agents that are active against gram-positive organisms. Like
van-comycin, teicoplanin is bacteriostatic against staphylo-cocci,
streptococci, and enterococci. Gram-positive rods, such as Bacillus anthracis, Corynebacterium diph-theriae, Clostridium tetani, and Clostridium perfringens, are also
sensitive to the glycopeptides. The glycopep-tides are not effective against
gram-negative rods, my-cobacteria, or fungi.
Vancomycin is poorly absorbed
from the gastrointesti-nal tract, resulting in high concentrations in the
feces. In neutropenic patients and others with altered gastroin-testinal mucosa
with denudation, significant oral ab-sorption of vancomycin may occur and may
be accom-panied by additive toxicity if rapid infusion or large parenteral
doses of the drug are given concomitantly. Except for the treatment of
staphylococcal enterocolitis and pseudomembranous colitis, it is administered
intra-venously. Peak serum levels are achieved 2 hours after intravenous (IV)
administration, and about 55% is bound to serum protein. The therapeutic range
is a trough concentration between 5 and 15 μg/mL, and the peak should stay below 60 μg/mL to avoid side effects. In normal adults
the serum half-life is 5 to 11 hours. With impaired renal function, the
half-life is 7 to 9 days. The dose of vancomycin must be carefully adjusted to
avoid toxicity or ineffective treatment, especially in pa-tients undergoing
hemodialysis. Pediatric oncology pa-tients with normal renal function may require
van-comycin dosage regimens that are substantially greater than predicted.
Similar studies in adult patients with hematological malignancies have
suggested a larger dosage requirement as well, owing to an increased vol-ume of
distribution.
After IV administration,
vancomycin diffuses into serous cavities and across inflamed but not normal
meninges. It can be used in the treatment of meningitis with susceptible
organisms. It is also given via ventricu-loatrial or ventriculoperitoneal
shunts when these be-come infected.
Renal excretion is
predominant, with 80 to 90% of an administered dose eliminated in 24 hours.
Only small amounts appear in the stool and bile after intravenous
administration.
Teicoplanin, like vancomycin,
is not absorbed from the intestinal tract. Peak plasma levels are achieved
about 2 hours after intramuscular administration. The drug distributes widely
in tissues; plasma protein binding is about 90%. The half-life approximates 50
hours, which is considerably longer than that of vancomycin, and may make it
useful for outpatient administration. Like van-comycin, teicoplanin is excreted
by the kidneys.
Vancomycin and teicoplanin
display excellent activity against staphylococci and streptococci, but because
of the wide availability of equally effective and less toxic drugs, they are second-line drugs in the treatment of most
infections. As antistaphylococcal
agents they are less effective than β-lactam
cephalosporin antibiotics, such as nafcillin and cefazolin. They have attained
much wider use in recent years as a consequence of the emer-gence of
methicillin-resistant S. aureus
(MRSA) infec-tions, in particular the growing importance of Staph-ylococcus epidermidis infections
associated with the use of
intravascular catheters and in patients with peri-tonitis who are on continuous
ambulatory peritoneal dialysis.
Vancomycin is also an
effective alternative therapy for the treatment of staphylococcal enterocolitis
and en-docarditis. The combination of vancomycin and either streptomycin or
gentamicin acts synergistically against enterococci and is used effectively for
the treatment or prevention of enterococcal endocarditis. Teicoplanin
demonstrates similar synergy.
Staphylococcal vascular shunt
infections in persons undergoing renal dialysis have been successfully treated
with vancomycin. Vancomycin in oral form can also be used in patients in whom C. difficile colitis is not re-sponding
to metronidazole.
Teicoplanin, although not
available in the United States, has been used to treat a wide range of
gram-posi-tive infections, including endocarditis and peritonitis. It is not as
effective as the β-lactams, but its actions are similar to those of vancomycin
against staphylococcal infections.
An increased prevalence of
MRSA has resulted in a greater use of vancomycin for this disorder. High-grade
resistance of pneumococci to penicillin may also neces-sitate vancomycin
therapy. Enterococci that are resist-ant to vancomycin are emerging as major
nosocomial pathogens. These strains are generally resistant to a number of
other antibiotics, such as penicillin, ampi-cillin, and gentamicin, which
limits treatment options. The possibility of transferring these resistance
determi-nants to other gram-positive organisms, like S. aureus, is a valid concern. It is therefore necessary to limit
the use of vancomycin to treatment of serious infections caused by
methicillin-resistant staphylococci and situations in which allergies preclude
the use of other antibiotics.
The major adverse effect
associated with vancomycin therapy is ototoxicity, which may result in
tinnitus, high-tone hearing loss, and deafness in extreme instances. More
commonly, the intravenous infusion of van-comycin can result in chills, fever,
and a maculopapular skin rash often involving the head and upper thorax (red
man syndrome). Red man syndrome is associated with increased levels of serum
histamine. Vancomycin is rarely nephrotoxic when used alone. Teicoplanin rarely
causes red man syndrome or nephrotoxicity.
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