C H A P T E R 8
Anti-infective agents
87
Gastrointestinal toxicity
GI toxicity is very common with many of the anti-
infectives. Many of these agents have direct toxic effects
on the cells lining the GI tract, causing nausea, vomiting,
stomach upset or diarrhoea, and such effects are some-
times severe (see Box 8.6). There is also some evidence
that the death of the microorganisms releases chemi-
cals and toxins into the body, which can stimulate the
chemoreceptor trigger zone (CTZ) in the medulla and
induce nausea and vomiting.
In addition, some anti-infectives are toxic to the
liver. These drugs can cause hepatitis and even liver
failure. When people are taking drugs known to be toxic
to the liver (e.g. many of the cephalosporins) they should
be monitored closely and the drug should be stopped at
any sign of liver dysfunction.
Neurotoxicity
Some anti-infectives can damage or interfere with the
function of nerve tissue, usually in areas where drugs
tend to accumulate in high concentrations. For example,
the aminoglycoside antibiotics collect in the eighth
cranial nerve and can cause dizziness, vertigo and loss
of hearing. Hydroxychloroquine, which is used to treat
malaria and some other rheumatoid disorders, can accu-
mulate in the retina and optic nerve and cause blindness.
Other anti-infectives can cause dizziness, drowsiness,
lethargy, changes in reflexes and even hallucinations
when they irritate specific nerve tissues.
Hypersensitivity reactions
Allergic or hypersensitivity reactions reportedly occur
with many antimicrobial agents. Most of these agents,
which are protein bound for transfer through the
cardiovascular system, are able to induce antibody for-
mation in susceptible people. With the next exposure
to the drug, immediate or delayed allergic responses
may occur. In severe cases, anaphylaxis can occur,
which can be life-threatening. Some of these drugs have
demonstrated cross-sensitivity (e.g. penicillins, cephalo-
sporins), and care must be taken to obtain a complete
health history before administering one of these drugs. It
is important to determine what the allergic reaction was
and when the person experienced it (e.g. after first use
of the drug, or after years of use). Some people report
having a drug allergy, but closer investigation indicates
that their reaction actually constituted an anticipated
effect or a known adverse effect of the drug. Proper
interpretation of this information is important to allow
treatment of a person with a drug to which the person
reported a supposed allergic reaction but which would
be very effective against a known pathogen.
Superinfections
One offshoot of the use of anti-infectives, especially
broad-spectrum anti-infectives, is destruction of the
normal flora.
Superinfections
are infections that occur
when opportunistic pathogens that were kept in check
by the “normal” bacteria have the opportunity to invade
tissues. Common superinfections include vaginal or GI
yeast infections, which are associated with antibiotic
therapy, and infections caused by
Proteus
and
Pseu-
domonas
throughout the body, which are a result of
broad-spectrum antibiotic use. If people receive drugs
that are known to induce superinfections, they should be
monitored closely for any signs of a new infection—sore
patches in the mouth, vaginal itching, diarrhoea—and
the appropriate treatment for any superinfection should
be started as soon as possible.
Chloramphenicol (
Chloromycetin
), an older antibiotic,
prevents bacterial cell division in susceptible bacteria.
Because of the potential toxic effects of this drug, its
use is limited to serious infections for which no other
antibiotic is effective. Chloramphenicol produces a “grey
syndrome” in neonates and premature babies, which is
characterised by abdominal distention, pallid cyanosis,
vasomotor collapse, irregular respiration and even
death. In addition, the drug may cause bone marrow
depression, including aplastic anaemia that can result
in death. These effects are seen even with the use of the
ophthalmic and otic forms of the drug. Although the use
of chloramphenicol is severely limited, it has stayed on
the market because it is used to treat serious infections
caused by bacteria that are not sensitive to any other
antibiotic. It is available in oral, IV, ophthalmic and
otic forms.
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BOX 8.5
Serious adverse effects of antibiotic
treatment
Meropenem (
Merrem IV
), an IV antibiotic, inhibits the
synthesis of bacterial cell walls in susceptible bacteria.
It is used to treat intra-abdominal infections and some
cases of meningitis caused by susceptible bacteria.
Meropenem almost always causes very uncomfortable
gastrointestinal effects; in fact, use of this drug has been
associated with potentially fatal pseudomembranous
colitis. It also results in headache, dizziness, rash
and superinfections. Because of its toxic effect on
gastrointestinal cells, it is used only in those infections
with proven sensitivity to meropenem and reduced
sensitivity to less toxic antibiotics.
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BOX 8.6
Severe gastrointestinal toxicity resulting
from anti-infective treatment
