Antimicrobials · Macrolides
The facts most likely to be tested
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Azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, effectively blocking the translocation step.
Azithromycin (single 1 g dose) is effective for Chlamydia trachomatis urethritis/cervicitis; per 2021 CDC, doxycycline is now first-line, with azithromycin first-line in pregnancy.
Azithromycin is the preferred agent for prophylaxis against Mycobacterium avium complex (MAC) in patients with HIV and a CD4 count < 50 cells/mm³.
Azithromycin is a primary treatment for community-acquired pneumonia (CAP), particularly when used in combination with beta-lactams to cover atypical pathogens like Mycoplasma pneumoniae and Legionella.
Azithromycin carries a significant risk of QT interval prolongation, which can lead to Torsades de Pointes, especially in patients with pre-existing cardiac conditions or those on other QT-prolonging medications.
Azithromycin is the drug of choice for the treatment of pertussis (whooping cough) in both infected patients and as post-exposure prophylaxis for close contacts.
Azithromycin is the preferred treatment for chancroid caused by Haemophilus ducreyi, which presents as a painful genital ulcer with associated suppurative inguinal lymphadenopathy.
Vignette unlocked
A 24-year-old female presents to the clinic complaining of mucopurulent vaginal discharge and post-coital bleeding. She reports a new sexual partner and inconsistent condom use. Physical examination reveals cervical motion tenderness and an erythematous, friable cervix. A nucleic acid amplification test (NAAT) is positive for Chlamydia trachomatis. The patient has no known drug allergies.
What is the most appropriate pharmacologic treatment for this patient?
Azithromycin
This vignette tests treatment for Chlamydia trachomatis; per 2021 CDC, doxycycline 100 mg BID x7 days is first-line, with single-dose azithromycin as an alternative (first-line in pregnancy).
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High yield triage
Classification
Macrolide antibiotic; protein synthesis inhibitor.
Indications
Community-acquired pneumonia, chlamydia, pertussis, and MAC prophylaxis.
Mechanism of Action
Binds to 50S ribosomal subunit to inhibit translocation.
Side Effects
GI upset (diarrhea/nausea); QT prolongation; ototoxicity.
Contraindications / Monitoring
History of cholestatic jaundice; monitor QTc interval in high-risk patients.
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Mechanism of Action
Azithromycin binds reversibly to the 50S ribosomal subunit of susceptible organisms. This action inhibits RNA-dependent protein synthesis by blocking the exit tunnel and preventing peptide chain elongation. It is primarily bacteriostatic, though it can be bactericidal at high concentrations against specific pathogens.
Unique Properties
Distinguished by a long half-life (approx. 68 hours), allowing for once-daily dosing and short courses. It exhibits high tissue penetration and accumulates within phagocytes, facilitating targeted delivery to sites of infection.
Indications
First-line for community-acquired pneumonia (often with a beta-lactam); for chlamydia trachomatis it is an alternative (doxycycline is first-line per 2021 CDC; azithromycin first-line in pregnancy). It is the drug of choice for pertussis (post-exposure prophylaxis) and Mycobacterium avium complex (MAC) prophylaxis in HIV patients with CD4 < 50 cells/µL.
Pharmacokinetics
Undergoes extensive hepatic metabolism and biliary excretion; no dose adjustment is required for renal impairment. It is a weak inhibitor of CYP3A4, though less prone to drug-drug interactions than erythromycin.
Side Effects & Adverse Events
Commonly causes GI distress including nausea, vomiting, and abdominal pain. QT interval prolongation is a major concern, potentially leading to Torsades de Pointes. Rare but serious risks include cholestatic jaundice and ototoxicity at high doses.
Contraindications
Hypersensitivity to macrolides is an absolute contraindication. Use with extreme caution in patients with pre-existing QT prolongation or those taking other drugs that prolong the QT interval due to the risk of fatal arrhythmias.
Monitoring
Monitor for signs of hepatotoxicity (jaundice, elevated LFTs) in patients with pre-existing liver disease. Perform an ECG if the patient is on concurrent QT-prolonging medications or has known cardiac risk factors.
Clinical Pearls
Often tested as the preferred agent for atypical pneumonia (e.g., Mycoplasma pneumoniae). Remember it as the standard treatment for chancroid (Haemophilus ducreyi). Always consider the risk of arrhythmia in elderly patients with electrolyte imbalances.