Macrolides

Macrolides: Overview

Macrolides are a class of antibiotics known for their activity against Gram-positive bacteria, atypicals, and some Gram-negative bacteria. They are commonly used for respiratory infections, skin infections, and sexually transmitted infections (STIs). The most commonly used macrolides are Azithromycin, Clarithromycin, and Erythromycin.

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Common Macrolides:

• Azithromycin
• Clarithromycin
• Erythromycin

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Spectrum:

1. Azithromycin:

   • Gram-positive: Limited, covers Streptococcus species (especially Streptococcus pneumoniae), MSSA (less reliable for MSSA than other options)
   • Gram-negative: Limited, but effective against H. influenzae and Moraxella
   • Atypicals: Good coverage of Legionella, Chlamydia, Mycoplasma, and Mycobacterium avium complex (MAC)
   • Anaerobes: No significant anaerobic coverage

2. Clarithromycin:

   • Gram-positive: Streptococcus species, MSSA (better activity than Azithromycin for Gram-positive)
   • Gram-negative: Limited, similar to Azithromycin with activity against H. influenzae and Moraxella
   • Atypicals: Covers Legionella, Chlamydia, Mycoplasma, and MAC
   • Anaerobes: No significant anaerobic coverage

3. Erythromycin:

   • Gram-positive: Streptococcus species, MSSA (less effective than newer macrolides)
   • Gram-negative: Limited, some activity against H. influenzae and Neisseria but resistance is common
   • Atypicals: Good coverage of Legionella, Chlamydia, Mycoplasma, Treponema (syphilis)
   • Anaerobes: No significant anaerobic coverage

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Key Uses:

1. Azithromycin:

   • Respiratory infections: First-line for community-acquired pneumonia (CAP) and sinusitis, particularly in atypical pneumonia (Mycoplasma, Legionella).
   • Sexually transmitted infections (STIs): Effective for Chlamydia and used as part of combination therapy for gonorrhea.
   • Mycobacterium avium complex (MAC): Used in the prophylaxis and treatment of MAC infections in HIV patients.
   • Traveler’s diarrhea: Occasionally used to treat traveler’s diarrhea caused by Campylobacter or E. coli.

2. Clarithromycin:

   • Respiratory infections: Effective for sinusitis, bronchitis, and pneumonia caused by atypicals and Streptococcus.
   • Helicobacter pylori: Used in combination therapy for the eradication of H. pylori (peptic ulcer disease).
   • Skin infections: Occasionally used for mild skin infections due to Streptococcus or MSSA.

3. Erythromycin:

   • Respiratory infections: Historically used for pneumonia and pharyngitis, though less favored now due to resistance and side effects.
   • STIs: Still used for syphilis in penicillin-allergic patients.
   • Gastrointestinal motility agent: Often used off-label to stimulate gut motility in conditions like gastroparesis.

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Key Side Effects:

• GI distress: Erythromycin and Clarithromycin are notorious for causing gastrointestinal upset (nausea, vomiting, diarrhea) due to stimulation of motility receptors. Azithromycin is generally better tolerated.
• QT interval prolongation: All macrolides, especially Azithromycin and Erythromycin, can cause QT interval prolongation, increasing the risk of arrhythmias, particularly in patients on other QT-prolonging medications.
• Drug interactions: Clarithromycin and Erythromycin inhibit cytochrome P450 (CYP3A4) enzymes, leading to significant drug interactions with medications like statins and anticoagulants. Azithromycin has fewer interactions and is preferred when there are concerns about drug interactions.
• Resistance concerns: Increasing resistance to macrolides, particularly Streptococcus pneumoniae in respiratory infections, has led to more selective use of macrolides, particularly in regions with high resistance rates.

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Key Notes:

• Azithromycin: Favored for its once-daily dosing and long half-life, allowing for shorter courses of therapy. It is well tolerated and has fewer drug interactions compared to other macrolides.
• Clarithromycin: More potent than Azithromycin for Gram-positive organisms and used in H. pylori treatment, but more likely to cause GI upset and drug interactions.
• Erythromycin: Less commonly used due to side effects and resistance, but still useful in specific cases (e.g., gastroparesis, syphilis in penicillin allergy).

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Summary:

• Azithromycin: Preferred for respiratory infections, STIs, and MAC infections. It has excellent tolerability and fewer drug interactions.
• Clarithromycin: Useful in respiratory infections, H. pylori, and skin infections, but causes more GI side effects and drug interactions.
• Erythromycin: Mostly replaced by newer macrolides, but still used for syphilis in penicillin-allergic patients and as a prokinetic agent for gastroparesis.