Macrolide

Key takeaways

Macrolide belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Macrolide to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Macrolide from memory before moving on to harder problems.

Reference excerpt

Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. Some macrolides have antibiotic or antifungal activity and are used as pharmaceutical drugs. Rapamycin is also a macrolide and was originally developed as an antifungal, but has since been used as an immunosuppressant drug and is being investigated as a potential longevity therapeutic. Macrolides are a diverse group with many members of very different properties:

Macrolides with 14-, 15-, or 16-membered rings and two attached sugar molecules are antibiotics that bind to bacterial ribosomes, the key representative being erythromycin. The term "macrolide antibiotics" tend to refer to just this class. Some macrolides with very large (20+ membered) rings are immunosuppresants, the prototypical one being rapamycin. Some 23-membered macrolides are also antibiotics that bind to the 50S part of the bacterial ribosome, see streptogramin A. Polyene antimycotics are also technically macrolides.

Definition In general, any macrocyclic lactone having greater than 8-membered rings are candidates for this class. The macrocycle may contain amino nitrogen, amide nitrogen (but should be differentiated from cyclopeptides), an oxazole ring, or a thiazole ring. Benzene rings are excluded, in order to differentiate from tannins. Also lactams instead of lactones (as in the ansamycin family) are excluded. Included are not only 12-16 membered macrocycles but also larger rings as in tacrolimus.

History The first macrolide discovered was erythromycin, which was first used in 1952. Erythromycin was widely used as a substitute to penicillin in cases where patients were allergic to penicillin or had penicillin-resistant illnesses. Later macrolides developed, including azithromycin and clarithromycin, stemmed from chemically modifying erythromycin; these compounds were designed to be more easily absorbed and have fewer side-effects (erythromycin caused gastrointestinal side-effects in a significant proportion of users).

Uses Antibiotic macrolides are used to treat infections caused by Gram-positive bacteria (e.g., Streptococcus pneumoniae) and limited Gram-negative bacteria (e.g., Bordetella pertussis, Haemophilus influenzae), and some respiratory tract and soft-tissue infections. The antimicrobial spectrum of macrolides is slightly wider than that of penicillin, and, therefore, macrolides are a common substitute for patients with a penicillin allergy. Beta-hemolytic streptococci, pneumococci, staphylococci, and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have been shown to be effective against Legionella pneumophila, Mycoplasma, Mycobacterium, some Rickettsia, and Chlamydia. Macrolides are not to be used on nonruminant herbivores, such as horses and rabbits. They rapidly produce a reaction causing fatal digestive disturbance. It can be used in horses less than one year old, but care must be taken that other horses (such as a foal's mare) do not come in contact with the macrolide treatment. Macrolides can be administered in a variety of ways, including tablets, capsules, suspensions, injections and topically.

Mechanism of action

Antibacterial Macrolides are protein synthesis inhibitors. The mechanism of action of macrolides is inhibition of bacterial protein biosynthesis, and they are thought to do this by preventing peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid (similarly to chloramphenicol) as well as inhibiting bacterial ribosomal translation. Another potential mechanism is premature dissociation of the peptidyl-tRNA from the ribosome. Macrolide antibiotics bind reversibly to the P site on the 50S subunit of the bacterial ribosome. This action is considered to be bacteriostatic. Macrolides are actively concentrated within leukocytes, and thus are transported into the site of infection.

Immunomodulation

Diffuse panbronchiolitis The macrolide antibiotics erythromycin, clarithromycin, and roxithromycin have proven to be an effective long-term treatment for the idiopathic, Asian-prevalent lung disease diffuse panbronchiolitis (DPB). The successful results of macrolides in DPB stems from controlling symptoms through immunomodulation (adjusting the immune response), with the added benefit of low-dose requirements. With macrolide therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil granulocyte proliferation but also lymphocyte activity and obstructive secretions in airways. The antimicrobial and antibiotic effects of macrolides, however, are not believed to be involved in their beneficial effects toward treating DPB. This is evident, as the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of the macrolide-resistant bacterium Pseudomonas aeruginosa, macrolide therapy still produces substantial anti-inflammatory results.

Examples

Antibiotic macrolides US FDA-approved:

Azithromycin – unique; does not extensively inhibit CYP3A4 Clarithromycin Dirithromycin – discontinued but was US FDA approved Erythromycin

Not approved in the US by FDA but approved in the other countries by respective national authorities:

Carbomycin A Josamycin Kitasamycin Midecamycin/midecamycin acetate Oleandomycin Spiramycin – approved in the EU, and in other countries Troleandomycin – used in Italy and Turkey Tylosin/tylocine – used in animals Roxithromycin Not approved as a drug for medical use:

Boromycin (not a member of the classical 14–16-membered class)

Ketolides Ketolides are a class of antibiotics that are structurally related to the macrolides. They are used to treat respiratory tract infections caused by macrolide-resistant bacteria. Ketolides are especially effective, as they have two ribosomal binding sites. Ketolides include:

Telithromycin – the first and only approved ketolide Cethromycin Solithromycin

Fluoroketolides Fluoroketolides are a class of antibiotics that are structurally related to the ketolides. The fluoroketolides have three ribosomal interaction sites. Fluoroketolides include:

Solithromycin – the first and so far only fluoroketolide (not yet approved)

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Macrolide

Start with the simplest possible case. Write down what Macrolide claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Macrolide before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Macrolide ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Macrolide

In research: Macrolide appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Macrolide in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Macrolide is common in secondary-school and first-year university syllabi. It links to neighbouring topics Macrolides, so understanding it makes those chapters shorter.
In everyday life: Look for Macrolide outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Macrolide in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Macrolide means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Macrolide out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Macrolide in simple terms?

Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products.

Why does Macrolide matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Macrolide?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Macrolide.