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P A R T 2
Chemotherapeutic agents
mediators, leucocytes, lymphocytes, antibodies and
locally released enzymes and chemicals. When this
response is completely functional and all of the neces-
sary proteins, cells and chemicals are being produced by
the body, it can isolate and eliminate foreign proteins,
including bacteria, fungi and viruses. However, if a
person is immunocompromised for any reason (e.g. mal-
nutrition, age, acquired immune deficiency syndrome
[AIDS], use of immunosuppressant drugs), the immune
system may be incapable of dealing effectively with the
invading organisms. It is difficult to treat any infections
in such people for two reasons: (1) anti-infective drugs
cannot totally eliminate the pathogen without causing
severe toxicity in the host; and (2) these people do not
have the immune response in place to deal with even a
few invading organisms. Immunocompromised people
present a significant challenge to healthcare providers.
In helping these people cope with infections, prevention
of infection and proper nutrition are often as important
as drug therapy.
Resistance
Resistance
can be natural or acquired, and refers to the
ability over time to adapt to an antibiotic and produce
cells that are no longer affected by a particular drug.
Because anti-infectives act on specific enzyme systems
or biological processes, many microorganisms that do
not use that system or process are not affected by a par-
ticular anti-infective drug and are said to have a natural
or intrinsic resistance. When prescribing a drug for
treatment of an infection, this innate resistance should
be anticipated. The selected drug should be one that is
known to affect the specific microorganism causing the
infection.
Since the advent of anti-infective drugs, micro
organisms that were once very sensitive to the effects of
particular drugs have begun to develop acquired resist-
ance to the agents (see Box 8.3). This can result in a
serious clinical problem. The emergence of resistant
strains of bacteria and other organisms poses a threat.
Anti-infective drugs may no longer control potentially
life-threatening diseases and uncontrollable epidemics
may occur.
Acquiring resistance
Microorganisms develop resistance in a number of ways,
including the following:
• Producing an enzyme that deactivates the
antimicrobial drug. For example, some strains of
bacteria that were once controlled by penicillin
now produce an enzyme called penicillinase, which
inactivates penicillin before it can affect the bacteria.
This occurrence led to the development of new drugs
that are resistant to penicillinase.
• Changing cellular permeability to prevent the drug
from entering the cell or altering transport systems
to exclude the drug from active transport into the
cell.
• Altering binding sites on the membranes or ribosomes,
which then no longer accept the drug.
• Producing a chemical that acts as an antagonist to the
drug.
Most commonly, the development of resistance
depends on the degree to which the drug acts to elimi-
nate the invading microorganisms that are most sensitive
to its effects. The cells that remain may be somewhat
resistant to the effects of the drug, and, with time, these
cells form the majority in the population. These cells
differ from the general population of the species because
of slight variations in their biochemical processes or
biochemicals. The drug does not cause a mutation
of these cells; it simply allows the somewhat different
cells to become the majority or dominant group after
elimination of the sensitive cells. Other microbes may
develop resistance through actual genetic mutation.
A mutant cell survives the effects of an antibiotic and
divides, forming a new colony of resistant microbes with
a genetic composition that provides resistance to the
anti-infective agent.
Vancomycin (
Vancocin
) is an antibiotic that interferes
with cell wall synthesis in susceptible bacteria. It was
developed as a result of a need for a drug that could be
used both in people who are intolerant to or allergic to
penicillin and/or cephalosporins and in the treatment
of people with staphylococcal infections that no longer
respond to penicillin or cephalosporins. This anti-
infective drug can be used orally or intravenously to
treat life-threatening infections when less toxic drugs
cannot be used. It is used orally as prophylaxis against
bacterial endocarditis in people who cannot take
penicillins or cephalosporins and to treat staphylococcal
infections in people who cannot take these groups of
drugs.
Because vancomycin may be highly toxic, its use is
reserved for very special situations. It can cause renal
failure, ototoxicity, superinfections and a condition
known as “red man syndrome”, which is characterised
by sudden and severe hypotension, fever, chills,
paraesthesias and erythema or redness of the neck and
back. When it is the only antibiotic that is effective
against a specific bacterium, however, the benefits
outweigh the risks.
Usual dosage
Adult: 500 mg to 1 g PO or IV q 6 hours for 7–10 days.
Paediatric: 40 mg/kg/day PO or IV in four divided doses;
do not exceed 2 g/day.
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BOX 8.3
Bacterial resistance to an anti-infective
drug
