Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

β-LACTAMASE INHIBITORS
Route of administration
Aminopenicillins are acid stable and may be given
orally. However, ampicillin absorption is affected by
food (30–50% decrease in bioavailability). Amoxicillin
is less affected (20% decrease) but some studies suggest
that food delays absorption, so it is probably best given
on an empty stomach.
Adverse effects
Broad-spectrum penicillins have greater potential to
disturb normal flora than the narrow-spectrum penicillins
because they undergo biliary excretion and have
activity against obligate anaerobes. However, despite
widespread use of these drugs, there is little evidence of
adverse effects in dogs and cats.
Antipseudomonal penicillins
EXAMPLES
Carboxypenicillins (carbenicillin, ticarcillin), ureidopenicillins
(azlocillin, mezlocillin, piperacillin).
Antibacterial spectrum (Figs 8.5, 8.6)
● The antipseudomonal penicillins were developed to
improve the Gram-negative spectrum of penicillin,
particularly against Pseudomonas aeruginosa.
Increased activity against these organisms is achieved
through increased binding affinity for PBP3 and
improved penetration through the bacterial cell wall.
● Most Klebsiella, Citrobacter and Serratia and all
Enterobacter enterococci are resistant.
Gram positive
aerobes
Obligate
anaerobes
*excellent activity against P. aeruginosa
Gram negative
aerobes*
Penicillinaseproducing
Staphylococcus
Fig. 8.5 Antibacterial spectrum for carbencillin and
ticarcillin.
Gram positive
aerobes
Gram negative
aerobes*
● Ticarcillin is less active than azlocillin and piperacillin.
It has a similar spectrum to carbenicillin but is
2–4 times more active against P. aeruginosa.
● Azocillin, mezlocillin and piperacillin are described
as extended-spectrum antipseudomonal penicillins.
This results from their interaction with PBPs other
than those that bind aminopenicillins as well as their
resistance to some species-specific chromosomal
β-lactamases and increased penetration of Gramnegative
bacteria. They have greater activity against
Gram-negative bacteria, particularly Klebsiella and
P. aeruginosa, than carbenicillin as well as increased
activity against Bacteroides fragilis.
● Piperacillin is more active than azocillin and mezocillin.
It inhibits over 95% of P. aeruginosa isolates and
many Enterobacteriaceae and is active against many
anaerobes.
● Antipseudomonal penicillins are susceptible to
staphylococcal β-lactamase and to some common
Gram-negative β-lactamases. Ticarcillin is available in
various markets in combination with a clavulanate salt
which extends its activity against β-lactamase producing
Staphylococcus and Gram-negative bacteria.
● Combined use with an aminoglycoside is recommended
in any serious pseudomonal infection to
delay emergence of resistance and increase bacterial
kill, as a degree of immunosuppression is often
present in these patients.
Clinical applications
● The most common veterinary application for these
drugs is topical treatment of otitis externa due to P.
aeruginosa resistant to other drugs.
● They may also be used for systemic treatment infections
by Pseudomonas spp, usually in combination
with an aminoglycoside to delay the emergence of
resistance.
● When combined with clavulanate (see below), ticarcillin
is effective against many β-lactamase producing
strains of otherwise resistant Gram-negative bacteria
and Staphylococcus.
Route of administration
Carbenicillin, ticarcillin and piperacillin must be given
parenterally and high doses are required. Ticarcillin and
piperacillin can also be dissolved and used aurally to
treat otitis externa caused by Pseudomonas.
Obligate
anaerobes
*excellent activity against Pseudomonas
Penicillinaseproducing
Staphylococcus
Fig. 8.6 Antibacterial spectrum for piperacillin.
b-LACTAMASE INHIBITORS
Clavulanic acid
Mechanism of action
Clavulanic acid is a β-lactam drug (the first natural β-
lactam containing oxygen ever identified) that has little
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