Chemical structure of erythromycin.
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Eryc

Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea. Structurally, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desoamine), making it a compound very difficult to produce via synthetic methods. more...

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Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

History

Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate Erythromycin from the metabolic products of a strain of Streptomyces erythreus found in the samples. The product was subsequently launched in 1952 under the brand name Ilosone® (after the Philippine region of Iloilo where it was originally collected from). Erythromycin was formerly also called Ilotycin®. In 1981, Nobel laurate (1965 in chemistry) and Professor of Chemistry at Harvard University (Cambridge, MA) Robert B. Woodward and a large team of researchers reported the first stereocontrolled asymmetric chemical synthesis of Erythromycin A.

Available forms

Erythromycin is available in enteric-coated tablets, oral suspensions, opthalmic solutions, ointments, gels and injections.

Mechanism of action

Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translation of peptides.

Pharmacokinetics

Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused 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.

Metabolism

Most of erythromycin is metabolised by demethylation in the liver. Its main elimination route is in the bile, and a small portion in the urine. Erythromycin's half-life is 1.5 hours.

Side-effects

Gastrointestinal intestinal disturbances such as diarrhea, nausea, abdominal pain and vomiting are fairly common so it tends not to be prescribed as a first-line drug. More serious side-effects, such as reversible deafness are rare. Allergic reactions, while uncommon, may occur, ranging from urticaria to anaphylaxis. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrolysis are some other rare side effects that may occur.

Erythromycin has been shown to increase the probability of pyloric stenosis in children whose mothers took the drug during the late stages of pregnancy or while nursing.

Contraindications

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 (Ray et al 2004). Hence, erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap).

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Nocardiosis
From Gale Encyclopedia of Medicine, 4/6/01 by Carol A. Turkington

Definition

Nocardiosis is a serious infection caused by a fungus-like bacterium that begins in the lungs and can spread to the brain.

Description

Nocardiosis is found throughout the world among people of all ages, although it is most common in older people and males. While people with poor immunity are vulnerable to this infection, it sometimes strikes individuals with no history of other diseases. Nocardiosis is rare in AIDS patients. It is not transmitted by person-to-person contact.

Causes & symptoms

Nocardiosis is caused by a bacterium of the Nocardia species--usually N. asteroides, an organism that is normally found in the soil. The incubation period is not known, but is probably several weeks.

The bacteria can enter the human body when a person inhales contaminated dust. Less often, people can pick up the bacteria in contaminated puncture wounds or cuts.

Symptoms

The infection causes a cough similar to pneumonia or tuberculosis, producing thick, sometimes bloody, sputum. Other symptoms include chills, night sweats, chest pain, weakness, loss of appetite and weight loss. Nocardiosis does not, however, respond to short-term antibiotics.

Complications

In about one-third of patients, the infection spreads from the blood into the brain, causing brain abscesses. This complication can trigger a range of symptoms including severe headache, confusion, disorientation, dizziness, nausea and seizures, and problems in walking. If a brain abscess ruptures, it can lead to meningitis.

About a third of patients with nocardiosis also have abscesses in the skin or directly underneath the skin. They may also have lesions in other organs, such as the kidneys, liver, or bones.

Diagnosis

Nocardia is not easily identified from cultures of sputum or discharge. A doctor can diagnose the condition using special staining techniques and taking a thorough medical history. Lung biopsies or x-rays also may be required. Up to 40% of the time, however, a diagnosis can't be made until an autopsy is done.

Treatment

Treatment of nocardiosis includes bed rest and high doses of medication for a period of 12 to 18 months, including sulfonamide drugs or a combination of trimethoprim-sulfamethoxazole (Bactrim, Septra). If the patient doesn't respond to these drugs, antibiotics such as ampicillin (Amcill, Principen) or erythromycin (E-Mycin, Eryc) may be tried.

The abscesses may need to be drained and dead tissue cut away. Other symptoms are treated as necessary.

Prognosis

Nocardiosis is a serious disease with a high mortality rate. If it has been diagnosed early and caught before spreading to the brain, the prognosis is better. Even with appropriate treatment, however, the death rate is still 50%. Once the infection reaches the brain, the death rate is above 80%. This outcome is most commonly seen in patients with a weakened immune system.

Key Terms

Abscess
A localized area of infection in a body tissue. Abscesses in the brain or skin are possible complications of nocardiosis.
Meningitis
An infection of the outer covering of the brain (meninges) that can be caused by either bacteria or a virus.

Further Reading

For Your Information

    Books

  • Handbook of Diseases, edited by June Norris. Springhouse, PA: Springhouse Corp., 1996.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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