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P A R T 2
Chemotherapeutic agents
occurs.
Ocular preparations are contraindicated for
viral, fungal or mycobacterial infections of the eye,
which could be exacerbated by loss of bacteria of the
normal flora.
Use with caution in people with hepatic
dysfunction,
which could alter the metabolism of the
drug
, and in those with renal disease,
which could inter-
fere with the excretion of some of the drug.
Also use
with caution in breastfeeding women
because macro
lides secreted in breast milk can cause diarrhoea and
superinfections in the infant
and in pregnant women
because of potential adverse effects on the developing
fetus
; use only if the benefit clearly outweighs the risk to
the fetus or the infant.
Adverse effects
Relatively few adverse effects are associated with the
macrolides. The most frequent ones, which involve
the direct effects of the drug on the GI tract, are often
uncomfortable enough to limit the use of the drug.
These include abdominal cramping, anorexia, diar-
rhoea, vomiting and pseudomembranous colitis. Other
effects include neurological symptoms such as confu-
sion, abnormal thinking and uncontrollable emotions,
which could be related to drug effects on the CNS mem-
branes; hypersensitivity reactions ranging from rash to
anaphylaxis; and superinfections related to the loss of
normal flora.
Clinically important drug–drug interactions
Increased serum levels of digoxin occur when digoxin is
taken concurrently with macrolides. People who receive
both drugs should have their digoxin levels monitored
and dose adjusted during and after treatment with the
macrolide.
In addition, when oral anticoagulants, theophyl-
lines, carbamazepine or corticosteroids are administered
concurrently with macrolides, the effects of these drugs
reportedly increase as a result of metabolic changes in
the liver. People who take any of these combinations
may require reduced dose of the particular drug and
careful monitoring.
Clinically important drug–food interactions
Food in the stomach decreases absorption of oral macro
lides. Therefore, the antibiotic should be taken on an
empty stomach with a full, 150 mL glass of water 1 hour
before or at least 2 to 3 hours after meals.
LINCOSAMIDES
The lincosamides (Table 9.9) are similar to the mac-
rolides but are more toxic. These drugs include
clindamycin (
Cleocin
) and lincomycin (
Lincocin
).
Therapeutic actions and indications
The lincosamides react at almost the same site in bacte-
rial protein synthesis and are effective against the same
strains of bacteria (Figure 9.2). These drugs are used in
the treatment of severe infections when a less toxic anti-
biotic cannot be used.
Pharmacokinetics
The lincosamides are rapidly absorbed from the GI tract
or from IM injections and are metabolised in the liver
and excreted in the urine and faeces. These drugs cross
the placenta and enter breast milk (see contraindications
and cautions).
Clindamycin has a half-life of 2 to 3 hours. It is avail-
able in parenteral and oral forms, as well as in topical
and vaginal forms for the treatment of local infections.
Lincomycin has a half-life of 5 hours. It can be given
orally, IM or IV.
Contraindications and cautions
Use lincosamides with caution in people with hepatic or
renal impairment, which could interfere with the metab-
olism and excretion of the drug. Use during pregnancy
and breastfeeding only if the benefit clearly outweighs
the risk to the fetus or neonate.
Adverse effects
Severe GI reactions, including fatal pseudomembranous
colitis, have occurred, limiting the usefulness of lincos
amides. However, for a serious infection caused by a
susceptible bacterium, a lincosamide may be the drug of
choice. Some other toxic effects that limit usefulness are
pain, skin infections and bone marrow depression.
MONOBACTAM ANTIBIOTIC
The only monobactam antibiotic currently available for
use is aztreonam (
Azactam
) (Table 9.9).
Therapeutic actions and indications
Among the antibiotics, aztreonam’s structure is unique,
and little cross-resistance occurs. It is effective against
gram-negative enterobacteria and has no effect on
gram-positive or anaerobic bacteria. Aztreonam disrupts
bacterial cell wall synthesis, which promotes leakage of
cellular contents and cell death in susceptible bacteria
(see Figure 9.2). The drug is indicated for the treatment of
urinary tract, skin, intra-abdominal and gynaecological
infections, as well as septicaemia caused by suscepti-
ble bacteria, including
E. coli
,
Enterobacter
,
Serratia
,
Proteus
,
Salmonella
,
Providencia
,
Pseudomonas
,
Citro-
bacter
,
Haemophilus
,
Neisseria
and
Klebsiella.
