Macrolide Therapy

What Are Macrolides?

Macrolides are a class of medications that are used to treat several types of bacterial infections. Therefore, macrolides are a broad-spectrum antibiotic that inhibits bacterial growth (bacteriostatic) and prevents the progression of bacterial infections. Examples of macrolides include Azithromycin, Clarithromycin, Erythromycin, Fidoximycin, etc. In other words, macrolides are a class of antibiotics with a large lactone ring containing complex chemical structure produced by different strains of Streptomyces (a type of soil-borne bacteria). They work by preventing the 50S ribosomal subunit from being formed, which is how they inhibit protein synthesis and bacterial growth.

What Is Macrolide Therapy?

The use of macrolides to prevent or treat several infections like pneumonia (refers to inflammation of the air sacs in the lungs filled with fluids), pharyngitis (sore throat), sinusitis (inflammation of the sinuses), tonsilitis (inflammation of the tonsils), certain skin and ear infections, etc., are known as macrolide therapy. Moreover, macrolides are also used to treat sexually transmitted infections like gonorrhea (gonococcal infection) and chlamydia (chlamydial infection). In the traditional triple therapy protocol, Clarithromycin treats Helicobacter pylori infections. During macrolide therapy, the primary mode of action is bacteriostatic (inhibiting bacterial growth). However, depending on the type of microbe or at high doses, they may also be bactericidal (killing the causative bacteria).

What Are the Indications of Macrolide Therapy?

Macrolides have antibacterial and antifungal properties. Hence, they are used in antimicrobial therapy. Moreover, the first macrolide used in therapy was Erythromycin in 1952. The use of macrolide as an antibiotic in treating a wide range of bacterial infections has been approved by the U.S. (United States) Food and Drug Administration (FDA).

Indications of macrolide therapy are as follows:

• Pneumonia.

• Tonsilitis.

• Pharyngitis.

• Sinusitis.

• Uncomplicated skin infections.

• Otitis media (infections causing inflammation of the ear) in children.

• Helicobacter pylori infections (Clarithromycin is used).

• Macrolides are frequently employed in the treatment of sexually transmitted infections such as gonococcal and chlamydial infections.

• Additionally, macrolides have been a cornerstone in treating atypical pneumonia, typically caused by pathogens like Mycoplasma pneumoniae, Legionella, and Chlamydia pneumoniae.

• Macrolide therapy has been shown to improve spirometry outcomes and quality of life for children and adults with non-cystic fibrosis bronchiectasis.

• Macrolides are crucial to COPD (chronic obstructive pulmonary disease) exacerbation therapy plans. These medications' anti-inflammatory and immunomodulating properties make them useful for treating COPD.

• In recent times, macrolides have also been used for COVID-19 infections due to its anti-inflammatory mechanism.

What Is the Mechanism of Action of Macrolides?

• Macrolides inhibit bacterial growth by inhibiting protein synthesis. The way macrolides work is based on their capacity to bind the bacterial 50S ribosomal subunit, which stops the synthesis of proteins in the bacteria.

• Once it binds, the macrolides block the enzyme peptidyltransferase from adding the succeeding amino acid connected to the tRNA (transfer ribonucleic acid), blocking mRNA (messenger RNA) translation and, more precisely, the growth of the peptide chain.

• Macrolides are bacteriostatic substances because they prevent protein synthesis but can potentially be bactericidal in high quantities.

• The interactions between macrolides, phospholipids, transcription factors, and other inflammatory cytokines are thought to cause their anti-inflammatory and immunomodulatory properties.

How Are Macrolides Administered?

Several factors should be considered before administering macrolides, including the strength of the drug, dosage, route of administration, clinical aims of the therapy, etc. Moreover, depending on the intended prescription and the purpose of therapy, macrolides can be administered through various routes. The most widely used form of these medications is as oral tablets, while they are also available as topical creams, intravenous medications, eye drops, etc.

The commonly prescribed dosage of some macrolides is as follows:

1. Erythromycin:

• Oral tablets 250 mg or 500 mg.

• Eye drops or ointments 0.5 %.

• Topical gels or solutions or creams 2 %.

2. Clarithromycin:

• Oral tablets 125 mg, 250 mg, 0r 500 mg.

• Powder reconstitution 125 mg for 5 mL of oral suspension.

3. Azithromycin:

• Oral tablets 100 mg, 250 mg, 500 mg, or 600 mg.

4. Fidaxocimin:

• Oral tablets 200 mg.

What Are the Adverse Effects of Macrolide Therapy?

Side effects of macrolide therapy include the following:

• Nausea and vomiting.

• Abdominal pain, the main cause of abdominal discomfort, is that macrolides are motilin agonists, which raise the possibility of gastrointestinal disturbances and adverse effects.

• Diarrhea.

• Macrolides tend to make the QT and QTc intervals in the cardiac cycle longer. Erythromycin shows the strongest tendency, and the lowest is Azithromycin.

• Patients are at risk for cardiac arrhythmias such as Torsades de Pointes, ventricular tachycardia, and ventricular fibrillation because of the increase in intervals. Torsades de Pointes is the most frequent arrhythmia caused by using macrolides.

• Recent research on macrolides has also revealed a connection between using these medications and sensorineural hearing loss. This hearing loss can be reversible or permanent and can occur at high and standard doses.

• Even though they are uncommon, serious side effects, including Stevens-Johnsons syndrome and toxic epidermal necrolysis, are possible and should be considered while giving these medications.

• Liver toxicity in pregnant women.

• Pyloric stenosis in newborns.

What Are the Contraindications for Macrolide Therapy?

Generally, macrolides are a safe class of antibiotics to use, although there are some relative contraindications because of their side effect profile and potential for drug interactions. Macrolide therapy may be contraindicated in the following cases:

• Because macrolides have arrhythmogenic properties, they should be avoided by patients having prolonged QT (electrocardiogram wave) intervals on electrocardiograms.

• Macrolides should not be used in patients with congenital disorders such as long QT syndrome type 2.

• Macrolides should be avoided by patients using Class Ia and Class III antiarrhythmic medications because both of these drug classes lengthen the QT interval and produce arrhythmias.

• Macrolides and some regularly used medications can interact and cause adverse effects. Drugs that can interact with macrolides are Carbamazepine, Cyclosporin, Astemizole, Theophylline, Terfenadine, etc.

• Due to potential negative effects on the mother or the unborn child, pregnant women should avoid macrolides, particularly Erythromycin.

Conclusion:

Macrolides are broad-spectrum antibiotics used to treat conditions like pneumonia, sinusitis, sore throat, skin infections, ear infections, etc. These drugs are highly potent and efficient in treating infections and possess antibacterial and antifungal properties. However, just like any other class of drugs, macrolides also have certain contraindications and side effects. Antibiotic overuse has resulted in a significant rise in resistance to several standard treatments. This problem also applies to macrolides; several organisms have also developed resistance against macrolides.