Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

PEPTIDE ANTIBIOTICS
PEPTIDE ANTIBIOTICS
Glycopeptides
EXAMPLES
Avoparcin, teicoplanin, vancomycin.
Mechanism of action
Glycopeptides inhibit synthesis of cell well peptidoglycan
and inhibit bacterial cell membrane permeability. They
also affect bacterial RNA synthesis. Vancomycin has had
limited use in veterinary medicine because of high cost
and the need for continuous IV infusion. However, the
emergence of MRSA infections in animals has resulted
in its greater use in veterinary practice. Teicoplanin
may be more useful as it has slightly better activity, can
be administered IM and has a long half-life. Avoparcin
was used extensively as a growth promoter in poultry
but has been withdrawn from most markets because it
may select for vancomycin-resistant enterococci which
may be a source of infection for immunocompromised
patients.
Antibacterial spectrum (Fig. 8.13)
Teicoplanin and vancomycin are bactericidal to most
Gram-positive aerobes and anaerobes as well as penicillinase-producing
Staphylococcus. Most Gram-negative
bacteria are resistant.
Clinical applications
Vancomycin
● Vancomycin is important in human medicine for
treating multidrug-resistant infections. It should not
be used in veterinary patients unless it is the only
alternative, when serious infections are resistant to
other antibiotics.
● The most common indication would be MRSA infections
or multidrug-resistant Enterococcus.
Gram positive
aerobes
Obligate
anaerobes
* Including MRSA
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus*
Fig. 8.13 Antibacterial spectrum for vancomycin and
teicoplanin.
● It is used to treat pseudomembranous colitis due to
Clostridium difficile in humans and may have a
similar application in animals, including rabbits and
hamsters.
Teicoplanin
● Teicoplanin has advantages over vancomycin as it
requires less frequent dosing, can be given IM
and has reduced potential for ototoxicity or
nephrotoxicity.
● Teicoplanin is used in human medicine to treat serious
infections, such as septicemia, endocarditis, bone and
joint infections caused by Gram-positive bacteria
resistant to other drugs, cystitis due to multidrugresistant
enterococci and catheter-associated staphylococcal
infections in neutropenic patients.
● Selection for resistant bacteria is a problem and there
is evidence that teicoplanin may be less active in vivo
than predicted in vitro.
Pharmacokinetics
Vancomycin
● Vancomycin is poorly absorbed after PO administration.
After IV administration penetration into tissues
is adequate but relatively poor. It distributes into
CSF if the meninges are inflamed.
● Half-life in dogs is shorter than in humans: 2 h vs
6 h.
● Most vancomycin is excreted by glomerular filtration
with a small amount in bile.
● Dosage alteration (based on monitoring plasma drug
concentrations) is required in patients with renal
failure.
Teicoplanin
● No pharmacokinetic studies have been reported in
small animals.
● It is not absorbed after PO administration in humans
but absorption after IM injection is excellent.
● Half-life in humans is 45–70 h after IV
administration.
● Penetration is poor across difficult body barriers.
● Elimination is almost entirely renal.
Route of administration
Vancomycin
● Vancomycin should not be administered IV rapidly
or as a bolus as thrombophlebitis, severe hypotension
and cardiac arrest (rare) have been reported.
Administer it over at least 30 min in a dilute
solution.
● IM, SC or IP routes should not be used.
● PO administration can be used to treat enteric infections
(C. difficile colitis).
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