Medical uses[edit]

Erythromycin can be used to treat bacteria responsible for causing infections of the skin and upper
respiratory tract,
including Streptococcus, Staphylococcus, Haemophilus and Corynebacterium genera. The following
represents MIC susceptibility data for a few medically significant bacteria:[11]

Haemophilus influenzae: 0.015 to 256 g/ml

Staphylococcus aureus: 0.023 to 1024 g/ml
Streptococcus pyogenes: 0.004 to 256 g/ml
Corynebacterium minutissimum: 0.015 to 64 g/ml
Available forms[edit]

Enteric-coated erythromycin capsule from Abbott Labs

Erythromycin is available in enteric-coated tablets, slow-release capsules, oral suspensions,

ophthalmic solutions, ointments, gels, enteric-coated capsules, non enteric-coated tablets, non
enteric-coated capsules, and injections. The following erythromycin combinations are available for
oral dosage:[12]

erythromycin base (capsules, tablets)

erythromycin estolate (capsules, oral suspension, tablets), contraindicated during pregnancy[13]
erythromycin ethylsuccinate (oral suspension, tablets)
erythromycin stearate (oral suspension, tablets)
For injection the available combinations are:[12]

erythromycin gluceptate
erythromycin lactobionate
For ophthalmic use

erythromycin base (ointment)

Adverse effects[edit]
Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very
common because erythromycin is a motilin agonist.[14] Because of this, erythromycin tends not to be
prescribed as a first-line drug. It may be useful in treating gastroparesis due to this promotility effect.
Intravenous erythromycin may also be used in endoscopy as an adjunct to clear gastric contents.
More serious side effects include arrhythmia with prolonged QT intervals including torsades de
pointes, and reversible deafness. Allergic reactions range
from urticaria to anaphylaxis. Cholestasis, StevensJohnson syndrome, and toxic epidermal
necrolysis are some other rare side effects that may occur.
Studies have shown evidence both for and against the association of pyloric stenosis and exposure
to erythromycin prenatally and postnatally.[15][16] Exposure to erythromycin (especially long courses at
antimicrobial doses, and also through breastfeeding) has been linked to an increased probability
of pyloric stenosis in young infants.[17][18] Erythromycin used for feeding intolerance in young infants
has not been associated with hypertrophic pyloric stenosis.[17]
Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant women in the
form of elevated serum glutamic-oxaloacetic transaminase and is not recommended during
pregnancy. Some evidence suggests similar hepatotoxicity in other populations.[19]
It can also affect the central nervous system, causing psychotic reactions, nightmares and night
sweats.[20]
It may also alter the effectiveness of combined oral contraceptive pills because of its effect on the
gut flora. Erythromycin is an inhibitor of the cytochrome P450 system, which means it can have a
rapid effect on levels of other drugs metabolised by this system, e.g., warfarin.

Interactions[edit]
Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular,
by isozymes of the CYP3A superfamily, CYP3A.[21] The activity of the CYP3A enzymes can be
induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect
the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates drugs that
are broken down by CYP3A such as simvastatin (Zocor), lovastatin (Mevacor),
or atorvastatin (Lipitor)are taken concomitantly with erythromycin, levels of the substrates
increase, often causing adverse effects. A noted drug interaction involves erythromycin and
simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Another
group of CYP3A4 substrates are drugs used for migraine such
as ergotamine and dihydroergotamine; their adverse effects may be more pronounced if
erythromycin is associated.[20] Earlier case reports on sudden death prompted a study on a large
cohort that confirmed a link between erythromycin, ventricular tachycardia, and sudden cardiac
death in patients also taking drugs that prolong the metabolism of erythromycin
(like verapamil or diltiazem) by interfering with CYP3A4.[22] Hence, erythromycin should not be
administered to people using these drugs, or drugs that also prolong the QT interval. Other
examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid,
withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Theophylline, which
is used mostly in asthma, is also contraindicated.
Erythromycin may affect neuromuscular transmission by acting presynaptically, so may produce or
worsen symptoms of myasthenia gravis in patients with pre-existing postsynaptic defects.
Exacerbations of myasthenia gravis have also been reported with the use of telithromycin and
azithromycin.[23]
Erythromycin and doxycycline can have a synergistic effect when combined and kill bacteria (E.
coli) with a higher potency than the sum of the two drugs together. This synergistic relationship is
only temporary. After approximately 72 hours, the relationship shifts to become antagonistic,
whereby a 50/50 combination of the two drugs kills less bacteria than if the two drugs were
administered separately.[24]

Pharmacology[edit]
Mechanism of action[edit]
Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher
concentrations,[25] but the mechanism is not fully understood. By binding to the 50s subunit of the
bacterial rRNA complex, protein synthesis and subsequent structure and function processes critical
for life or replication are inhibited.[25] Erythromycin interferes with aminoacyl translocation, preventing
the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex.
Without this translocation, the A site remains occupied, thus the addition of an incoming tRNA and
its attached amino acid to the nascent polypeptide chain is inhibited. This interferes with the
production of functionally useful proteins, which is the basis of this antimicrobial action.

Pharmacokinetics[edit]
Erythromycin is easily inactivated by gastric acid; therefore, all orally administered formulations are
given as either enteric-coated or more-stable salts or esters, such as erythromycin ethylsuccinate.
Erythromycin is very rapidly absorbed, and diffuses into most tissues and phagocytes. Due to the
high concentration in phagocytes, erythromycin is actively transported to the site of infection, where,
during active phagocytosis, large concentrations of erythromycin are released.[citation needed]

Metabolism[edit]
Most of erythromycin is metabolised by demethylation in the liver by the hepatic enzyme CYP3A4.
Its main elimination route is in the bile with little renal excretion, 2%-15% unchanged drug.
Erythromycin's elimination half-life ranges between 1.5 and 2.0 hours and is between 5 and 6 hours
in patients with end-stage renal disease. Erythromycin levels peak in the serum 4 hours after dosing;
ethylsuccinate peaks 0.5-2.5 hours after dosing, but can be delayed if digested with food.[26]
Erythromycin crosses the placenta and enters breast milk. The American Association of Pediatrics
determined erythromycin is safe to take while breastfeeding.[27] Absorption in pregnant patients has
been shown to be variable, frequently resulting in levels lower than in nonpregnant patients.[26]

Chemistry[edit]
Composition[edit]
Standard-grade erythromycin is primarily composed of four related compounds known as
erythromycins A, B, C, and D. Each of these compounds can be present in varying amounts and can
differ by lot. Erythromycin A has been found to have the most antibacterial activity, followed by
erythromycin B. Erythromycins C and D are about half as active as erythromycin A.[11][28] Some of
these related compounds have been purified and can be studied and researched individually.

Synthesis[edit]
Over the three decades after the discovery of erythromycin A and its activity as an antimicrobial,
many attempts were made to synthesize it in the laboratory. The presence of 10 stereospecific
carbons and several points of distinct substitution has made the total synthesis of erythromycin A a
formidable task.[29] Complete syntheses of erythromycins related structures and precursors such as
6-deoxyerythronolide B have been accomplished, giving way to possible syntheses of different
erythromycins and other macrolide antimicrobials.[30]Woodward successfully completed the synthesis
of erythromycin A.[31][32][33]

Erythromycin related compounds[edit]

Azithromycin
Carbomycin
 Cethromycin
Clarithromycin
Dirithromycin
Mitemcinal
Oleandomycin
Roxithromycin
Spiramycin
Telithromycin
Tylosin

History[edit]
Erythromycin was discovered by Abelardo Aguilar when working for the pharmaceutical company Eli
Lilly and Company as a researcher.[34]
In 1949 Abelardo B. Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly . Eli
Lillys research team, led by J. M. McGuire, managed to isolate erythromycin from the metabolic
products of a strain of Streptomyces erythreus (designation changed to "Saccharopolyspora
erythraea") found in the samples.
Lilly filed for patent protection of the compound and U.S. patent 2,653,899 was granted in 1953. The
product was launched commercially in 1952 under the brand name Ilosone (after
the Philippine region of Iloilo where it was originally collected). Erythromycin was formerly also called
Ilotycin.
In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at Harvard University Robert
B. Woodward (posthumously), along with a large number of members from his research group,
reported the first stereocontrolled asymmetric chemical synthesis of erythromycin A.
The antibiotic clarithromycin was invented by scientists at the Japanese drug company Taisho
Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of
erythromycin.
Scientists at Chugai Pharmaceuticals discovered an erythromycin-derived motilin agonist
called mitemcinal that is believed to have strong prokinetic properties (similar to erythromycin) but
lacking antibiotic properties. Erythromycin is commonly used off-label for gastric motility indications
such as gastroparesis. If mitemcinal can be shown to be an effective prokinetic agent, it would
represent a significant advance in the gastrointestinal field, as treatment with this drug would not
carry the risk of unintentional selection for antibiotic-resistant bacteria.

Society and culture[edit]

Cost[edit]
It is available as a generic medication and is inexpensive.[5] The wholesale price is between 0.03 and
0.06 USD per pill.[10]
In the United States in 2014 the price increased to seven dollars per tablet.[35]

Brand names[edit]
Brand names include Robimycin, E-Mycin, E.E.S. Granules, E.E.S.-200, E.E.S.-400, E.E.S.-400
Filmtab, Erymax, Ery-Tab, Eryc, Ranbaxy, Erypar, EryPed, Eryped 200, Eryped 400, Erythrocin
Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, MY-E, Pediamycin, Zineryt, Abboticin,
Abboticin-ES, Erycin, PCE Dispertab, Stiemycine, Acnasol, and Tiloryth.
See also[edit]