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THE MACROLIDES
I. History and Source
A. Erythromycin was discovered in 1952. It was isolated from Streptomyces erythreus which was obtained from a soil sample from the Phillipine islands.
B. Tylocin was isolated from a strain of Streptomyces fradiae found in soil from Thailand.
II. Chemistry
A. Erythromycin
1. Structure( Fig. 7a)
2. Other chemical characteristics
i. Consist of a high lactone ring with two sugars (desosamine and cladinose)
ii. Soluble in organic solvents. Slightly soluble in water.
iii. Effective at pH 8.
B. Tylosin(Fig. 7b)
1. Structure- another antibiotic substance with macrolide structure (C45H77NO17). The exact structural formula has not been elucidated.
2. Other Chemical Characteristics
a. Soluble in alcohols, esters, ketones, etc.
b. The compound is stable in solutions at pH 4-9.
III. Mechanism of Action
A. The macrolides inhibit protein synthesis by binding to 50S ribosomal subunits of sensitive microorganisms. They are bacteriostatic.
B. They can interfere with chloramphenicol which also binds at the 50S site.
VI. Absorption, Distribution and Excretion
A. Absorption
1. The macrolides are adequately absorbed when administered intramuscularly, orally and intravenously.
B. Distribution
1. They diffuse readily into intracellular fluids.
2. Antibacterial activity cannot be achieved in the brain and cerebrospinal fluid.
3. They penetrate into prostatic fluid, the placenta and fetal circulation.
C. Excretion
1. Approximately less than 20% of the drug is excreted in the urine.
2. The antibiotics are metabolized in the liver and concentrated in the bile.
V. Toxicity
A. Vomition and diarrhea - related to oral dosing of large doses.
B. Pain and some tissue irritation - related to I.M. injection.
C. Skin rashes (sensitivity) - related to local or topical application.
VII. Clinical Use
A. Antibacterial Spectrum of Macrolides
1. Includes gram-positive
2. Organisms resistant to tylosin are cross-resistant to other macrolides.
3. Use of macrolides in therapy of infections(see table)
_________________________________________________________________Gram-Positive Host Disease Tylosin Erythromycin
Organisms
_________________________________________________________________
Mycoplasma Turkey Chronic Drinking Water 92.5g/ton
Respiratory
disease
Treponia
Hydrosentenal Swine Swine dysentery 40-100gm/tn
----
Corynebacterium Cattle Liver abscesses Feed 8- ---- Swine/ Increase Feed 10-100g/ton 10g/ton
Chicken Efficiency ---- 10-70g/ton
185g/ton
_________________________________________________________________
In dogs and cats erythromycin is injected at 1-2 mg per pound body weight for conditions such as pneumonia, rhinitis, and secondary infections associated with distemper or feline panleukopenia.
STUDY QUESTIONS
1. Which antibiotics are commonly referred to as the macrolides?
2. Explain what is meant by the term macrolides.
3. Compare the mechanisms of action of macrolides, sulfonamides and tetracyclines.
4. Would you recommend any of these antibiotics in cases of bacterial meningitis? Why?.