Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CEPHALOSPORINS AND CEPHAMYCINS
are related structurally to benzylpenicillin and have a
β-lactam ring. Like penicillins, they inhibit cell wall
synthesis by preventing cross-linking of peptidoglycan.
However, unlike many penicillins, cephalosporins are
resistant to β-lactamase produced by Staphylococcus
spp. By convention, cephalosporins discovered before
1975 were spelled with a ‘ph’ and those discovered after
1975 with an ‘f’ but the recommended international
nonproprietary names have been changed now so that
they are all spelled with an ‘f’.
Gram positive
aerobes
Obligate
anaerobes
* MRSA are resistant
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus*
Mechanisms of resistance
Resistance to cephalosporins can occur due to reduced
permeability, enzymatic inactivation or absence of specific
PBPs. Constitutive and acquired resistance caused
by periplasmic β-lactamases against the different cephalosporins
defines the different cephalosporin classes.
Extracellular expression of β-lactamases and efflux
pumps has to some extent limited the use of the newer
cephalosporins in human medicine. Outbreaks of resistant
nosocomial infections have occurred in hospitals.
Some mutants have altered outer membrane permeability
as well as drug pump efflux activity and may show
cross-resistance to aminoglycosides, chloramphenicol,
fluoroquinolones, tetracyclines and trimethoprim.
Plasmid-mediated acquired resistance has also been
described.
Classification of cephalosporins
Cephalosporins are divided into first-, second-,
third- and fourth-generation groups plus antipseudomonal
cephalosporins (Table 8.5). Some of the drugs
listed in Table 8.5 are actually cephamycins (e.g. cefoxitin,
cefotetan, latamoxef) but they are included there as
cephalosporins because they have very similar
properties.
All groups include drugs that can be given parenterally
and oral preparations are also available for most
first-generation and a few third-generation drugs.
Spectrum of activity (Figs 8.9–8.11)
Gram positive
aerobes
Obligate
anaerobes
* MRSA are resistant
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus*
Fig. 8.9 Antibacterial spectrum for first-generation
cephalosporins.
Fig. 8.10 Antibacterial spectrum for second-generation
cephalosporins.
Gram positive
aerobes
Obligate
anaerobes
Gram negative
aerobes
Penicillinaseproducing
Staphylococcus*
* Varies from moderate to good depending on individual drug
MRSA are resistant
Fig. 8.11 Antibacterial spectrum for third-generation
cephalosporins.
Clinical applications
First-generation
● Skin infections caused by Staphylococcus
● Soft tissue infections due to susceptible organisms
● Urinary tract infections (but not prostate)
● Osteomyelitis
● Discospondylitis
● Bacterial conjunctivitis (cefalonium)
Second-generation
● Similar to orally active cephalosporins in dogs and
cats.
● In human medicine and some veterinary institutions,
the human-approved formulation cefuroxime is used
for surgical prophylaxis, particularly for orthopedic
surgery because of good activity against appropriate
opportunistic pathogens.
Third-generation
● Because of cost, availability of cheaper alternatives
and the potential to select for resistant bacteria,
third-generation cephalosporins should be reserved
in small animal practice for serious infections caused
by Gram-negative aerobic and facultatively anaerobic
bacteria, especially Enterobactericaceae.
● They may also be indicated for the treatment of
urinary tract infections caused by otherwise resistant
bacteria.
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