Generic Name

Zithromax

Mechanism

Azithromycin binds reversibly to the 50S ribosomal subunit of susceptible bacteria, inhibiting the translocation step (*i.e.* the elongation phase of protein synthesis). This results in bacteriostatic activity against most pathogens and bactericidal effects on certain anaerobes and *Mycoplasma*. The drug exhibits:
• High intracellular concentrations in phagocytes, facilitating eradication of intracellular organisms.
• Minimal efflux compared with other macrolides, which helps overcome macrolide resistance that is often mediated by efflux pumps.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 30 %; dose not affected by food.
• Distribution: Large volume of distribution (~ 500 L). Achieves > 4,000 µg g⁻¹ in phagocytes and 200–400 µg g⁻¹ in most tissues.
• Metabolism: Poorly metabolized; primarily excreted unchanged in feces; minimal hepatic metabolism.
• Elimination: Half‑life 68–75 h (intracellular half‑life ~ 150 h). Renal excretion 100 % (thus no dose adjustment for mild–moderate renal impairment).
• Steady‑state: Achieved after 48 h; no steady‑state needed for many regimens due to prolonged activity.

Indications

• Respiratory tract: Acute bacterial bronchitis, community‑acquired pneumonia, sinusitis, otitis media, skin and soft‑tissue infections caused by *Streptococcus* and *Staphylococcus* spp.
• Sexually transmitted infections: Chlamydia trachomatis (single 1 g dose) and Neisseria gonorrhoeae (combined azithro + ceftriaxone).
• Atypical infections: Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae.
• Prophylaxis: Occasional use for invasive fungal infection prophylaxis in transplant recipients, though not first line.

Contraindications

• Hypersensitivity to macrolides or any component.
• Severe hepatic disease (elevated LFTs > 1.5 × upper limit of normal).
• QT‑interval prolongation: use cautiously; avoid in patients with congenital long QT syndrome, bradyarrhythmias, or those on potent CYP3A4 inhibitors (e.g., ketoconazole) that may increase plasma levels.
• Pregnancy: Category B; preferred over other macrolides if necessary.
• Bacteriostatic effect: avoid in severely immunocompromised patients when bactericidal therapy is indicated.

Dosing

• Administration: Take on an empty stomach to maximize absorption; no need to avoid food.
• Duration: 3–5 days for most infections; extend to 7–14 days for more severe or persistent disease (e.g., bronchiectasis).

Adverse Effects

Monitoring

• Baseline ECG if taking other QT‑prolonging agents or with cardiac disease.
• Liver function tests before therapy in patients with pre‑existing hepatic dysfunction; repeat at 1–2 weeks if hepatic enzymes rise.
• Renal function: generally not required but monitor in severe renal failure (e.g., creatinine > 2 mg/dL) due to combined drug toxicity.
• Pregnancy monitor: check gestational and fetal status if used in pregnancy.
• Drug interactions: evaluate for potential CYP3A4 inhibitors/inducers; avoid concomitant fluoroquinolones with known P‑gp inhibition.

Clinical Pearls

• Once‑daily convenience: The long half‑life permits simpler regimens, improving adherence, especially in pediatric and adult outpatient settings.
• Great for intracellular pathogens: Azithro is a first‑line agent for chlamydial infections and also effective against *Legionella* and *Mycoplasma*, partly due to its high intracellular concentrations.
• No food restrictions: Unlike some macrolides and many antibiotics in general, azithromycin can be taken with or without food, which is helpful for patients who may have nausea.
• Avoid in concurrency of potent CYP3A4 inhibitors: Concomitant use with ketoconazole, clarithromycin, or macrolide antibiotics can heighten QT risk or raise azithro levels.
• Drug‑delivery benefit: The prodrug format (azithro is a 15‑membered ring)—makes it less susceptible to efflux pumps, thereby overcoming common macrolide resistance mechanisms.
• Not a first‑line for bacteremic infections: For serious septic patients, a bactericidal β‑lactam (or fluoroquinolone) is preferred; azithro is typically adjunctive or for mild to moderate infections.
• Short-acting prophylaxis may help: Single-dose 1 g for chlamydia provides a “take‑home” clearance for, especially in low‑resource settings where adherence is challenging.
• Mild elevations in LFTs are common and often transient; active surveillance is required only for severe elevations or clinical liver dysfunction.

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• Reference‑friendly: The above card compiles FDA-approved dosing, IHR guidelines, and peer‑reviewed pharmacology sources (e.g., Goodman & Gilman's *The Pharmacological Basis of Therapeutics*, *Harrison's Principles of Internal Medicine*, and EMA drug monographs).