Macrolides, Tetracyclines & Fluoroquinolones
What examiners watch for is whether you can pair the right atypical-coverage antibiotic with the right syndrome and avoid the safety landmines. Macrolides (azithromycin, clarithromycin) cover atypical pneumonia (Mycoplasma, Chlamydophila, Legionella) and pertussis but prolong QT. Tetracyclines (doxycycline, minocycline) own the tick-borne illnesses — Rocky Mountain spotted fever, Lyme, ehrlichiosis — and CA-MRSA skin infections; avoid in pregnancy and in children under 8 (tooth staining, bone effects). Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) carry multiple black boxes — tendon rupture, peripheral neuropathy, aortic aneurysm, C. diff — and should be reserved when alternatives are inappropriate. All three classes prolong the QT interval; expect a vignette pairing one with another QT-prolonging drug.
📖 Overview
Macrolides (azithromycin) cover atypicals and are go-to for community-acquired pneumonia and pertussis. Doxycycline covers atypicals, tick-borne disease, community-acquired MRSA, and acne. Fluoroquinolones (ciprofloxacin, levofloxacin) are broad-spectrum with serious black-box warnings limiting routine use.
⚙️ Mechanism of Action
Macrolides: bind 50S ribosomal subunit → block protein synthesis. Tetracyclines: bind 30S → block aminoacyl-tRNA attachment. Fluoroquinolones: inhibit DNA gyrase + topoisomerase IV → block DNA replication.
💎 Board Pearls
- ⚡ QT prolongation: azithromycin + levofloxacin + ciprofloxacin (additive if also on SSRI/citalopram).
- 🦴 FQ BLACK BOX: tendon rupture (Achilles), aortic dissection risk, peripheral neuropathy, C. diff — reserve for when no alternative.
- ☀️ Doxycycline → photosensitivity; counsel on sunscreen.
- 🦷 Tetracyclines bind Ca²⁺ → tooth staining in <8 yrs old + fetus (avoid in pregnancy and young kids).
- 🐕 Doxycycline first-line for Lyme, Rocky Mountain Spotted Fever, early ehrlichiosis/anaplasmosis.
- 💡 FQs no longer recommended for uncomplicated UTI or acute sinusitis/bronchitis (FDA 2016).
- ⚠️ Ciprofloxacin + theophylline → ↑ theophylline levels (CYP1A2 inhibition).
💊 Drugs in This Class
- Azithromycin — Zithromax, Z-PakCAP, atypical pneumonia (Mycoplasma, Chlamydophila, Legionella), chlamydia, pertussis, MAC prophylaxis.
- Doxycycline — Vibramycin, DoryxCAP, tick-borne illness (Lyme, RMSF, ehrlichiosis), acne, chlamydia, CA-MRSA SSTI alternative, malaria prophylaxis.
- Ciprofloxacin — CiproComplicated UTI, pyelonephritis, prostatitis, traveler's diarrhea, inhalational anthrax, pseudomonal infections.
- Levofloxacin — LevaquinCAP (atypical coverage), complicated UTI, acute pyelonephritis, prostatitis, skin infections.
Practice Questions
Which of the following antibiotic class combinations carries the greatest risk of QT prolongation and should be used cautiously in patients already taking other QT-prolonging drugs (e.g., citalopram, antipsychotics)?
Sources
Ready to practice?
1,500+ AANP-style questions with rationales — free trial.