Macrolides are groups of antibiotics that are bacteriostatic agents & inhibit bacterial protein synthesis by binding reversibly to 50S ribosomal subunits of sensitive micro-organisms. It is a class of antibiotics derived from Saccharopolyspora erythraea (originally called Streptomyces erythreus), a type of soil-borne bacteria. Macrolides inhibit protein synthesis in bacteria by reversibly binding to the P site of the 50S unit of the ribosome prototypic macrolide is erythromycin; other clinically important macrolides include clarithromycin and azithromycin.
Types of Macrolides
Antibiotic macrolides
US FDA-approved
- Azithromycin
- Clarithromycin
- Erythromycin
- Fidaxomicin
- Telithromycin
Non-US FDA-approved
- Carbomycin A
- Josamycin
- Kitasamycin
- Midecamycin/midecamycin acetate
- Oleandomycin
- Solithromycin
- Spiramycin – approved in the EU, and in other countries
- Troleandomycin – used in Italy and Turkey
- Tylosin/tyrosine – used in animals
- Roxithromycin
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 currently the only fluoroketolide (not yet approved)
Non-antibiotic macrolides
The drugs tacrolimus, pimecrolimus, and sirolimus, which are used as immunosuppressants or immunomodulators, are also macrolides. They have similar activity to cyclosporin.
Antifungal drugs
Polyene antimycotics, such as amphotericin B, nystatin etc., are a subgroup of macrolides. Cruentaren is another example of an antifungal macrolide.
Toxic macrolides
A variety of toxic macrolides produced by bacteria have been isolated and characterized, such as the mycolactones.
Follow chart
| Macrolides |
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|---|---|
| Ketolides |
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| Lincosamides |
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| Streptogramins |
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Mechanism of action of Macrolides
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 ribosomal translation. Another potential mechanism is premature dissociation of the peptidyl-tRNA from the ribosome. Macrolide antibiotics do so by binding 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, a 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.
Indications/Uses of Macrolides
- Ear, nose and throat infections – such as otitis media (infection of the middle ear), labyrinthitis (infection of the inner ear), sinusitis (infection of the sinuses), tonsillitis (infection of the tonsils) and laryngitis (infection of the voice box).
- Chest infections – such as pneumonia (infection of the lining of the lung), bronchitis (infection of the airways of the lung) and whooping cough.
- Skin infections – such as eczema, psoriasis or acne that has become infected.
- Mouth and dental infections – such as gingivitis (infection of the gums) and a tooth abscess (infection in the root of a tooth).
- Sexually transmitted infections – such as chlamydia.
- Dental Abscess
- Sinusitis
- Bronchitis
- Bacterial Endocarditis Prevention
- Follicular Lymphoma
- Helicobacter Pylori Infection
- Legionella Pneumonia
- Mycobacterium avium-intracellular,
- Mycoplasma Pneumonia
- Nongonococcal Urethritis
- Otitis Media
- Pertussis
- Pharyngitis
- Pneumonia
- Skin and Structure Infection
- Skin or Soft Tissue Infection
- Strep Throat
- Tonsillitis/Pharyngitis
- Toxoplasmosis
- Upper Respiratory Tract Infection
- Acute Bacterial Exacerbation of Chronic Bronchitis
- Acute maxillary sinusitis
- Bacterial Infections
- Bartonellosis
- Community-Acquired Pneumonia
- A duodenal ulcer caused by Helicobacter pylori
- Infective Endocarditis
- Lyme Disease
- Mycobacterial Infection
- Otitis Media (OM)
- Streptococcal Pharyngitis
- Streptococcal tonsillitis
- Uncomplicated skin and subcutaneous tissue bacterial infections
Contraindications of Macrolides
- You should not take macrolide antibiotics if you are allergic to other macrolides or the ingredients in the tablets which include microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and povidone
- Macrolide antibiotics should not be used in people with a history of cholestatic jaundice and/or liver dysfunction associated with prior
- macrolide antibiotics use.
- or if you have hypokalemia (low blood potassium)
- Use of macrolide antibiotics with the following medications: cisapride, pimozide, astemizole, terfenadine, ergotamine, ticagrelor, ranolazine or dihydroergotamine is not recommended.
- It should not be used with colchicine in people with kidney or liver impairment.
- Concomitant use with cholesterol medications such as lovastatin or simvastatin.
- Hypersensitivity to macrolide antibiotics or any component of the product, erythromycin, or any macrolide antibiotics.
- QT prolongation or ventricular cardiac arrhythmias, including torsade de pointes.
Side Effects of Macrolides
The most common
- Diarrhea
- Nausea
- Stomach pain
- Vomiting
- Gas
- Heartburn
- Headache
- Change in taste
- Hives
- Itching
Common
- Swelling of the face, throat, eyes, hands, lips, ankles, feet, or lower legs
- Rash
- Hoarseness
- Difficulty swallowing or breathing
- Peeling or blistering skin
- Yellowing of the skin or eyes
- Extreme tiredness
- Lack of energy
- Loss of appetite
- Unusual bleeding or bruising
Less common
- Cough
- fever or chills
- hoarseness
- lower back or side pain
- painful or difficult urination
- fast or chaotic heartbeats
- skin reactions such as painful rash, red or purple spots on the skin, or blisters
- trouble breathing
- swelling of your face, lips, tongue, or throat
Rare
- Fever with or without chills
- nausea and vomiting
- severe stomach cramps and pain
- skin rash and itching
- stomach tenderness
- unusual bleeding or bruising
- watery and severe diarrhea, which may also be bloody
- yellow eyes or skin
Drug Interactions of Macrolides
- colchicine (Colcrys) while you take
- certain medicines called calcium channel blockers, such as: verapamil, amlodipine , diltiazem , or other medications containing these products
- cholesterol lowering medicines; you should not take these cholesterol-lowering medicines while taking
- simvastatin
- atorvastatin
- carbamazepine
- cisapride
- cobimetinib
- digoxin, a medicine used to treat heart failure
- midazolam, a medicine used to induce sleep before operations
- cyclosporin, a medicine used to prevent organ transplant rejection or to treat certain problems with the immune system
- cisapride, a medicine used to treat gastrointestinal problems
- conivaptan
- dihydroergotamine
- dihydroergotamine intranasal
- flibanserin
- itraconazole
- lomitapide
- lovastatin
- lurasidone
- naloxegol
- phenytoin
- pimozide
- regorafenib
- rifampin
- simvastatin
- terfenadine and astemizole, medicines used to treat allergies
- pimozide, an antipsychotic medicine
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