Classification of macrolides

• Telithromycin
  A semisynthetic erythromycin derivative. It is often grouped separately as a ketolide rather than a conventional macrolide.

• Fidaxomicin
  A macrocyclic antibiotic mainly used for Clostridioides difficile infection.

Mechanism of action of azithromycin

• Azithromycin is a macrolide-type antibiotic (technically an azalide).
• It reversibly binds to 23S rRNA of the 50S bacterial ribosomal subunit.
• This blocks translocation and elongation of the growing peptide chain, thereby inhibiting bacterial protein synthesis.
• It also interferes with assembly of the 50S ribosomal subunit.
• Its action is usually bacteriostatic, though it can be bactericidal against some highly susceptible organisms at high concentrations.

Uses of azithromycin

1. Respiratory tract infections
   • Community-acquired pneumonia, especially atypical organisms: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella
   • Acute bacterial exacerbation of chronic bronchitis
   • Sinusitis, pharyngitis, tonsillitis, and otitis media when appropriate
2. Sexually transmitted infections
   • Chlamydia trachomatis urethritis/cervicitis: alternative regimen where doxycycline is unsuitable
   • Chancroid due to Haemophilus ducreyi
3. Pertussis
   • Treatment and post-exposure prophylaxis for Bordetella pertussis. It is the preferred macrolide in young infants.
4. Mycobacterial infections
   • Prevention and treatment of disseminated Mycobacterium avium complex (MAC), always as part of an appropriate combination regimen.
   • Part of multidrug regimens for some nontuberculous mycobacterial pulmonary infections.
5. Other infections
   • Some enteric infections, including traveller's diarrhea and typhoid in susceptible strains
   • Campylobacter enteritis
   • Bartonella henselae infection, such as cat-scratch disease
   • Alternative agent in penicillin-allergic patients for selected susceptible infections

Adverse effects

Common

• Gastrointestinal upset: nausea, diarrhea, abdominal pain, vomiting
• Headache, dizziness
• Rash or mild hypersensitivity reaction

Important but uncommon

• QT-interval prolongation and torsades de pointes/arrhythmia
  Avoid or use particular caution in patients with known long QT syndrome, bradycardia, low potassium or magnesium, significant heart disease, or concurrent QT-prolonging drugs.
• Hepatotoxicity: elevated liver enzymes, hepatitis, cholestatic jaundice, rarely hepatic failure.
• Hypersensitivity: urticaria, angioedema, anaphylaxis, and rare serious cutaneous reactions such as SJS/TEN.
• C. difficile-associated diarrhea/colitis.
• Transient hearing impairment or tinnitus, mainly with high doses or prolonged treatment.
• Exacerbation of myasthenia gravis.
• Infantile hypertrophic pyloric stenosis in neonates exposed during the first weeks of life.

Mechanism of action of penicillin

1. They bind irreversibly to penicillin-binding proteins (PBPs), especially transpeptidases.
2. This inhibits the final transpeptidation (cross-linking) step of peptidoglycan cell-wall synthesis.
3. The bacterial cell wall becomes weak and cannot withstand osmotic pressure.
4. Activation of bacterial autolytic enzymes (autolysins) contributes to cell-wall breakdown.
5. The bacterium undergoes osmotic lysis and death.

Mechanism of action of cyclosporine

1. It enters T lymphocytes and binds to an intracellular immunophilin called cyclophilin.
2. The cyclosporine-cyclophilin complex inhibits calcineurin, a calcium/calmodulin-dependent phosphatase.
3. Normally, calcineurin dephosphorylates NFAT (nuclear factor of activated T cells), allowing NFAT to enter the nucleus.
4. With calcineurin inhibited, NFAT remains phosphorylated in the cytoplasm.
5. This reduces transcription of IL-2 and other cytokines such as IL-4, IFN-gamma, and TNF.
6. Result: reduced T-cell activation, proliferation, and cytokine-mediated immune response.