Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CEPHALOSPORINS AND CEPHAMYCINS
There are no approved human formulations of ceftiofur
but the impact on bacterial resistance of widespread
use of a third-generation cephalosporin in
food-producing animals may be of concern.
● Cefovecin (Convenia ® ) is registered in some markets
for use in canine skin and soft tissue infections associated
with Staphylococcus intermedius, β-hemolytic
streptococci, Escherichia and Pasteurella multocida;
canine urinary tract infections associated with
Escherichia and Proteus spp; feline skin and soft
tissue infections associated with Pasteurella multocida,
Fusobacterium spp, Bacteroides spp, Prevotella
oralis, β-hemolytic streptococci and Staphylococcus
intermedius; and feline urinary tract infections associated
with Escherichia.
Antipseudomonal parenteral cephalosporins
● These drugs are used in human medicine to treat
septicemias caused by Pseudomonas and other Gramnegative
pathogens in neutropenic patients.
● They have had limited use to date in veterinary medicine
but cefoperazone could be useful in small animal
practice to treat serious infections, especially against
Enterobacteriaceae such as Pseudomonas aeruginosa,
not susceptible to less expensive agents or if
aminoglycosides are excluded due to potential
toxicity.
Fourth generation
● Uses in human medicine include treatment of nosocomial
or community-acquired lower respiratory
tract infections, bacterial meningitis and urinary
tract infections.
● As they have particular value in human therapeutics,
they are unlikely to be used much in domestic animals
in the near future.
Pharmacokinetics
The pharmacokinetic features and toxicity of the cephalosporins
and cephamycins are similar to those of penicillins
except that they cross the placenta well. In
addition, they can be used in patients that are hypersensitive
to penicillins although about 5% of human
patients show cross-reactivity between cephalosporins
and penicillins.
They are primarily excreted by the kidney (with a few
exceptions). Some penetrate the CSF well but not the
orally active drugs. Elimination is relatively rapid for
most except cefovecin.
Oral cephalosporins
The pharmacokinetic features of the oral cephalosporins
are similar to those of aminopenicillins. They are
rapidly and largely absorbed after oral administration
in dogs and cats, though poorly and erratically absorbed
in horses and ruminants. Effects of ingesta on systemic
availability vary (see Table 8.2).
Cephalosporins are largely confined to extracellular
fluids and pass poorly across biological membranes,
although inflammation enhances passage across some
membrane barriers.
Most orally active cephalosporins have short halflives
(usually less than 1 h) and are excreted largely
unchanged in urine.
Parenteral cephalosporins
Most parenteral cephalosporins are rapidly and well
absorbed after IM or SC injection. IV formulations are
licensed for human but not veterinary use.
Most half-lives are short (usually less than 1 h) and
excretion is largely renal, although some hepatic metabolism
occurs for some of these drugs. The exception is
cefovecin which has a very long elimination half-life
following subcutaneous administration. Half-life at the
registered dose is 5.5 days in dogs and 6.9 days in cats.
The antimicrobial activity of cefovecin following a
single injection lasts up to 14 days.
Other routes
Cefalonium (Cepravin ® ) is available in some markets as
an ophthalmic ointment for treatment of bacterial conjunctivitis
in dogs and cats. It is available as an intramammary
in the treatment of mastitis in cattle.
Adverse effects
● Adverse reactions to cephalosporins are uncommon.
Allergic reactions are rare and in humans 95% of allergic
reactions are not cross-reactive with penicillin.
● Vomiting and diarrhea may occur in monogastric
animals; administering the drug with a meal may
alleviate this.
● While it has been demonstrated that cephalosporins,
particularly cefalothin, have the potential to cause
nephrotoxicity, the risk of this adverse effect appears
minimal when conventional dosages are given to
patients with normal renal function.
● Some of these drugs (cefamandole, cefoperazone,
latamoxef) have been implicated in causing bleeding
problems in humans. The significance of this for
animal patients is unclear as veterinary use of these
drugs is limited but caution would seem advisable in
patients receiving anticoagulant therapy or those
with warfarin-type rodenticide toxicity.
● In vitro, cephalosporins have synergistic or additive
activity with aminoglycosides against some bacteria
including Enterobacteriaceae such as Pseudomona
aeruginosa. However, concurrent use of cephalosporins
with other potentially nephrotoxic drugs (e.g.
aminoglycosides or amphotericin B) is controversial;
they could cause additive nephrotoxicity, though this
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