Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

PRINCIPLES OF ANTIBACTERIAL THERAPY
Therefore it is imperative that antibacterial agents be
used prudently; that is, only when an infectious process
is either identified definitively or considered most probably
present and the infection is believed likely to progress
without medical therapy.
Because of the theoretical and possibly practical potential
for some antibacterials to reduce protein production
(e.g. aminoglycosides, chloramphenicol, lincosamides,
macrolides, tetracyclines), concurrent antibacterial medications
need to be selected carefully when immunizing
animals, especially with nonadjuvant killed vaccines
(which generally induce a lesser immune response than
adjuvant killed or attenuated live vaccines).
Selection or promotion of resistance
Although many previously fatal bacterial infections can
now be treated successfully with antibacterial drugs, the
widespread use of these agents has resulted in other
problems, such as emergence of antibacterial-resistant
pathogens and the resultant rising health-care costs
as new drugs are developed to counteract drug
resistance.
Antibacterial agents do not cause bacteria to become
resistant but their use preferentially selects resistant
populations of bacteria. Some genes that code for resistance
have been identified in bacterial cultures established
before antibacterial agents were used. Indeed, the
ability of micro-organisms to produce antibiotics
depends on the presence of mechanisms to overcome
their effects. These mechanisms are not infrequently
transferable to other organisms.
Antibacterial drug resistance can emerge in various
ways, the most clinically important being R (resistance)
plasmids. R plasmids are cytoplasmic genetic elements
that can transfer drug resistance to previously susceptible
bacteria. This can occur between species and genera
and may involve genes that impart resistance to various
unrelated antibacterial agents.
Acquired resistance is not a problem in all bacterial
species. For example, Gram-positive bacteria (with
some exceptions, including Staphylococcus spp) are
often unable to acquire R plasmids (and thus acquire
resistance through mutation, a slower process), whereas
resistance is an increasing problem in many Gramnegative
pathogens such as the Enterobacteriaceae.
The intestine is a major site of transfer of antibacterial
resistance. This is particularly important when antibacterial
agents are used in animals managed intensively
and in contact with fecal material, an enormous reservoir
of intestinal bacteria.
Nosocomial infections
In veterinary hospitals, nosocomial infection (infection
acquired during hospitalization) by resistant bacteria is
an emerging problem, though apparently neither as
prevalent nor as serious as that currently experienced in
human hospitals. Bacteria most frequently implicated in
veterinary hospitals have been Klebsiella, Escherichia,
Proteus and Pseudomonas spp.
Factors predisposing to nosocomial infections include
age extremes (young or old), severity of disease, duration
of hospitalization, use of invasive support systems,
surgical implants, defective immune responses and prior
antibacterial drug use.
The drugs with greatest potential to suppress components
of the endogenous flora that normally prevents
colonization by pathogenic enteric bacteria are those
most active against obligate anaerobic bacteria
(chloramphenicol, lincosamides, penicillins) and those
undergoing extensive enterohepatic recycling (chloramphenicol,
lincosamides, tetracyclines). Agents generally
lacking this effect include aminoglycosides, fluoroquinolones
and sulfonamides with and without trimethoprim.
Cephalosporins are a major risk factor for
nosocomial enterococcal infection in humans.
Hypersensitivity
Hypersensitivity reactions to antibacterial agents are
reported less frequently in veterinary medicine than in
human patients, where they constitute 6–10% of all
drug reactions. To induce an allergic response, drug
molecules must be able to form covalent bonds with
macromolecules such as proteins. Bonding with the
protein carrier enables reaction with T lymphocytes and
macrophages. The reactive moiety is usually a drug
metabolite, e.g. the penicilloyl moiety of penicillins and
the sulfonamide metabolite hydroxylamine.
● Hypersensitivity reactions depend on the combination
of antigen and antibody and are usually not dose
related. The first episode cannot be anticipated,
although atopic individuals reportedly have a greater
tendency to develop drug allergies.
● Hypersensitivity reactions have been reported most
frequently in veterinary patients with cephalosporins,
penicillins and sulfonamides.
● Doberman pinschers appear to have an increased
risk of sulfonamide hypersensitivity, possibly due to
delayed sulfonamide metabolism. Other breed predispositions
have not been reported.
● The probability of an anaphylactoid reaction (i.e.
direct histamine release that is not immunologically
mediated) is increased with penicillin preparations
containing methylcellulose as a stabilizer.
Drug hypersensitivity may manifest in different ways.
● Acute anaphylaxis is associated with IgE-triggered
mast cell degranulation and characterized by one or
more of the following signs: hypotension, bronchospasm,
angioedema, urticaria, erythema, pruritus,
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