Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

8
Antibacterial drugs
Jill E Maddison, A David J Watson and Jonathan Elliott
PRINCIPLES OF ANTIBACTERIAL
THERAPY
History
Antibacterial drugs are chemical substances that suppress
the growth of microbes and may eventually destroy
them. They are produced by either natural fermentation
or chemical synthesis. Those derived from substances
produced by various microbial species (bacteria, fungi,
actinomycetes) are known as ‘antibiotics’ but not all
antibacterial agents are antibiotics: some are produced
solely by chemical synthesis, e.g. sulfonamides and
fluoroquinolones.
It had long been known that the application of various
moldy materials to wounds and infections assisted
healing but the possibility that this effect was due to
microbes was not recognized until the late 19th century.
The observations, developmental work and clinical
endeavors of Fleming, Chain and Florey heralded the
start of the revolution in antibiosis in the 20th century.
But the clinical use of antibiotic agents in effect represents
the practical, controlled and directed application
of phenomena that occur naturally and continuously in
soil, sewage, water and other natural habitats of
microbes.
Although Erhlich described the concept of ‘magic
bullets’ for treatment of syphilis in 1909, the modern
era of chemotherapy began in 1935 with the clinical use
of Prontosil (sulfonamide-chrysoidin). The ‘golden age’
arrived in 1941 with commercial production and clinical
use of penicillin. As a result of subsequent developments,
many previously fatal bacterial infections can
now be treated successfully but the widespread use of
antibacterial agents has resulted in substantial problems,
including the emergence and dissemination of
drug-resistant pathogens and increasing health-care
costs as new drugs are developed to counteract bacterial
resistance.
Aims of therapy
The goal of antibacterial therapy is to help the body
eliminate infectious organisms without toxicity to the
host. It is important to recognize that the natural defense
mechanisms of a patient are of primary importance in
preventing and controlling infection. Examples of
natural defenses against bacterial invasion are:
● the mucociliary escalator in the respiratory tract
● the flushing effect of urination
● the normal flora in the gastrointestinal tract.
All such mechanisms can be affected by disease or therapeutic
interventions.
Once microbial invasion occurs, various host
responses serve to combat the invading organisms,
including:
● the inflammatory response
● cellular migration and phagocytosis
● the complement system
● antibody production.
The difficulty of controlling infections in immunocompromised
patients emphasizes that antibacterial therapy
is most effective when it supplements endogenous
defense mechanisms rather than when acting as the sole
means of control.
Adverse effects
Antibacterial agents are not without the potential for
toxicity to the host and may cause:
● direct host toxicity (aminoglycosides, peptides)
● toxic interactions with other drugs
● interference with protective effects of normal host
microflora (by suppressing obligate anaerobes, for
example)
● selection or promotion of drug resistance (see
below)
● tissue necrosis at injection sites (tetracyclines)
● impairment of host immune or defense mechanisms
(chloramphenicol)
● reduced phagocytosis, chemiluminescence and
chemotactic activity of neutrophils (tetracyclines)
● inhibition of phagocytosis (aminoglycosides)
● hypersensitivity reactions (penicillins, sulfonamides)
● hepatic microsomal enzyme induction or inhibition
that interferes with their own metabolism as well
as that of concurrent medications
(chloramphenicol)
● residues in animal products for human
consumption (all antibacterials).
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