Françoise Van Bambeke

Eryhromycin

In: KUCERS' THE USE OF ANTIBIOTICS: A CLINICAL REVIEW OF ANTIBACTERIAL,
ANTIFUNGAL, ANTIPARASITIC AND ANTIVIRAL DRUGS
6TH EDITION

VO·LUME 1, pages 751-769

2010 Edward Arnold (Publishers) Ltd,

Ilotycin (CAS number: 114-07-8), thereafter renamed erythromycin
A, was first isolated at Eli Lilly from a strain' of Streptomyces erythreus
(McGuire et al., '1952). It is the first representative of the class of
macrolide antibiotics introduced for clinical use. Macrolides are
characterized by a macro cyclic lactone ring substituted by two sugars,
among which a desosamine confers a character of weak base
responsible for their ability to accumulate inside ~he cells. Erythromycin
is made of a 14-membered ring, substituted by a desosamine fu
position 5 and a cladinose in position 3. The empirical formula is
C37H67N013 and the molecular weight is 733.93; the chemical
structure is shown in Figure 59.1.
Erythromycin A base is very bitter, insoluble in water, and
inactivated by acid (including gastric secretions) as a result of an
intramolecular cyclization reaction leading to the formation of an
inactive spirocetal compound (Kirst and Sides, 1989). Effort has thus
been made to develop gastro-resistant formulations or ester prodrugs
to improve oral absorption. Current formulations of erythromycin base
include different formulations to be administered by the oral route and
a powder to be reconstituted for intravenous administration. The
availability of these differs from one country to another (tablets,
gastro-resistant capsules with delayed release, and granules or powder
for reconstitution of oral solutions). Erythromycin is also an active
ingredient in several preparations for topical applications. Stearate,
estolate, ethylsuccinate, lactobionate, and gluceptate are the salt and
ester forms used for clinical use. Most of the oral formulations need to
be administered 1 hour before a meal to ensure optimal oral absorption
because food affects drug absorption.

There are four key erythromycin compounds that have been used
clinically:
1. Erythromycin stearate (a salt).
2. Erythromycin ethyl succinate (an ester). These two preparations
are still susceptible to acid inactivation. Despite the fact that they
are marketed with a buffering agent or as film-coated or entericcoated
tablets, they should be administered at least 1 hour before
a meal.
3. Propinyl erythromycin ester lauryl sulfate (erythromycin estolate)
(the salt of an ester).
4. Stearate salt of 2/-acetyl ester of erythromycin (erythromycin
as citrate) (Tuominen et al., 1988). These last two formulations are
more resistant to inactivation by gastric acid and can be
admtnistered in the fastin~ state or after food.

Subsequent to the development of erythromycin, a series of semisynthetic
compounds with improved stability in an acidic environment
and oral bioavailability, as well as markedly improved pharmacologic
profiles, have been developed - these include clarithromycin,
roxithromycin, and azithromycin. In addition, some older macrolides,
including spiramycin, josamycin, and rosaramycin, remain available in
some regions. The availability of clarithromycin, roxithromycin, and
azithromycin has substantially reduced the use of erythromycin 'over
the last decade.

Erythromycin is mainly active against Gram-positive cocci, as well as
against a few Gram-negative bacteria" including Neisseria spp.,
Haemophilu.s spp., Legionella spp., as well as Chlamydia spp. and
Mycoplasma spp.