Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 8 ANTIBACTERIAL DRUGS
Bactericidal drugs
Under ideal laboratory conditions, bactericidal drugs
(aminoglycosides, cephalosporins, fluoroquinolones,
metronidazole, penicillins, potentiated sulfonamides)
cause the death of the microbe. These are preferred in
infections that cannot be controlled or eradicated by host
mechanisms, because of the nature or site of the infection
(e.g. bacterial endocarditis) or because of reduced immunocompetence
of the host (e.g. patient with immunosuppressive
illness or receiving immunosuppressive therapy).
However, successful clinical outcomes are reported in
humans with Gram-positive meningitis, endocarditis and
osteomyelitis treated with bacteriostatic drugs such as
clindamycin. For Gram-positive infections, the susceptibility
of the organism and the ability of the drug to penetrate
and concentrate in infected tissue are often more
important predictors of a successful clinical outcome
than whether the drug is bactericidal or bacteriostatic.
Bactericidal drugs are further classified as timedependent
or concentration-dependent drugs. Timedependent
drugs (penicillins and cephalosporins) are
slowly bactericidal. Plasma levels should be above MIC
for as long as possible during each 24-hour period
although no strict guidelines on the exact percentage of
time required have been established. For these drugs
there is little or no advantage (regarding proportion of
pathogens killed or duration of postantibiotic effect) in
achieving a peak plasma concentration (C max ) greater
than 2–4 times MIC.
For concentration-dependent drugs (aminoglycosides
and fluoroquinolones) the peak concentration achieved
(aminoglycosides, fluoroquinolones) and/or the area
under the plasma concentration versus time curve (fluoroquinolones)
predicts antibacterial success. For these
drugs the higher the peak plasma concentration:
● the greater the proportion of target bacteria killed
● the longer the postantibiotic effect.
For this second group the C max /MIC ratio is predictive
of treatment success; optimal regimens achieve a ratio
greater than 8 : 1.
Classification based on mechanism
of action
Major categories of antibacterial agents exert their antibacterial
action through one of four mechanisms.
● Inhibition of cell wall synthesis – bacitracin,
cephalosporins, penicillins, vancomycin
● Inhibition of cell membrane function – polymyxins
● Inhibition of protein synthesis – aminoglycosides,
chloramphenicol, lincosamides, macrolides,
tetracyclines
● Inhibition of nucleic acid synthesis or prevention of
repair – fluoroquinolones, metronidazole,
rifampicin, sulfonamides, trimethoprim
Classification based on antibacterial
spectrum
The veterinary student and clinician cannot hope to
remember all details of antibacterial activity for each
antibacterial drug. However, it is useful to have a reasonable
understanding of the broad patterns for each
drug class, particularly where drug classes are invariably
inactive against particular groups of bacteria. For
example, aminoglycosides and those fluoroquinolones
currently available are inactive against obligate anaerobes
while some narrow-spectrum penicillins (e.g.
penicillin G, aminopenicillins) are inactive against penicillinase-producing
Staphylococcus spp.
The term broad spectrum has traditionally ignored
obligate anaerobes, resulting in confusion in the minds
of practitioners about the spectrum of various drugs
relevant to clinical infections. An alternative approach
is to consider the activity of antibacterial drugs on the
basis of their activity against four groups of bacterial
pathogens: Gram-positive aerobes, Gram-negative
aerobes, Gram-positive anaerobes and Gram-negative
anaerobes. However, this is not particularly helpful in
small animal practice as (a) Gram-negative and Grampositive
anaerobes do not differ greatly in their antibacterial
susceptibility and any differences are difficult to
predict, and (b) this classification ignores the differences
in susceptibility pattern between penicillinaseproducing
Staphylococcus spp and other Gram-positive
aerobes. Therefore antibacterial drugs are discussed
here in relation to activity against the following four
quadrants:
● Gram-positive aerobes
● Staphylococcus spp (in small animal medicine most
clinically relevant infections are penicillinase
producing)
● Gram-negative aerobes
● obligate anaerobes.
Note that in this context, the term aerobe includes the
many bacteria that are facultative anaerobes such as the
Enterobacteriaceae family (E. coli et al), Pasteurella and
Vibrioaceae family.
The general spectrum of activity of each drug
class is depicted in the text in the section entitled
‘Antibacterial spectrum’ as illustrated in Figure 8.1.
The patterns shown here reflect the susceptibility of
broad bacterial groups to the drugs as they are used
clinically, i.e. they reflect acquired resistance patterns
in addition to the intrinsic susceptibility of the
organisms.
In addition, there are the atypical bacterial species
which do not Gram stain and fall outside the above
classification. These include Bartonella, Chlamydophila,
Mycobacterium, Mycoplasma and Rickettsia.
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