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Antifungal antibiotics

For much of the second half of the 20th century


nystatin, amphotericin and griseofulvin were the
principal antifungal antibiotics available, and
these were supplemented with a range of
synthetic imidazoles which were used primarily
for superfi cial rather than systemic fungal
infections.
The introduction of the triazole antifungals in the
1980s was a major advance and, more recently,
the echinocandins have further increased the
range of drugs available for severe infections.

12.1 Azoles
The azoles may be considered as two subgroups: the
older
imidazole drugs, the majority of which were introduced
as topical products or pessaries for the treatment of
superfi
cial infections by dermatophytes (skin pathogens),
Pityriasis species (causing fl aky skin and dandruff)
and C.
albicans , and the more recently developed, more
versatile
and, in some cases, much more expensive, triazoles.

Imidazoles
The imidazoles are a large and diverse group
of compounds
with activity against bacteria and protozoa
(metronidazole
and tinidazole), helminths (mebendazole)
and
fungi (clotrimazole, miconazole,
ketoconazole, econazole,
sulconazole and tioconazole).

Triazoles
Fluconazole (Figure 11.12 A) and itraconazole
were introduced
in the 1980s and posaconazole and voriconazole
much more recently.
Fluconazole is better absorbed from the
gastrointestinal
tract than itraconazole and, in addition to the
treatment
of dermatophytes, pityriasis and Candida
infections,

it is valuable in cases of cryptococcosis which, although


uncommon, is very dangerous in immunocompromised
patients. Itraconazole is used for similar infections to fl
uconazole
but, in addition, it is more commonly selected
as an alternative to amphotericin (see below) in cases of
systemic Aspergillus infection (again, more common in
the immunocompromised) and other rare systemic
mycoses. It is more frequently associated with liver toxicity
than fl uconazole.

Polyenes
Polyene antibiotics are characterized by
possessing a large
ring containing a lactone group and a
hydrophobic
region consisting of a sequence of four to
seven conjugated
double bonds. The only important polyenes
are
amphotericin B and nystatin.

Amphotericin B (Figure 11.12 C) is active against most


fungal pathogens and is used for systemic mycoses as a
potentially more toxic, but possibly more effective,
alternative
to itraconazole.
Nystatin is administered orally in the
treatment of C. albicans infections in the intestine or the
mouth (often referred to as thrush), and by cream or
pessary for skin or vaginal infections by that organism.

Echinocandins
The echinocandins are a new class of
semisynthetic
lipopeptide antibiotics that are
fungicidal towards
Aspergillus spp., Candida spp. and
Pneumocystis jirovecii
(previously known as P. carinii ).

Antiviral d rugs
HIV
There is a large and progressively
increasing variety of
antiretroviral agents available to
treat HIV, and their
use requires specialist knowledge

Protease inhibitor drugs available for the treatment of HIV

Herpes and c ytomegalovirus


i nfections

There are eight herpesviruses capable of causing human


infection, but of these the most important are:
the two herpes simplex viruses , HSV - 1 and HSV - 2,
which, respectively, cause cold sores on the face and lips,
and genital herpes
the varicella zoster virus causing chickenpox and
shingles
the Epstein Barr virus responsible for infectious
mononucleosis (glandular fever)
the cytomegalovirus (CMV) which may cause retinitis
(infl ammation of the retina) and, infrequently, similar
symptoms to infectious mononucleosis.

Viral h epatitis
Hepatitis, infl ammation of the liver,
can be caused by
various drugs and to xins, but
hepatitis due to viral infection
is more common.