Macrolide and Lincosamide Antibiotics

General Principles

  • Macrolide and lincosamide antibiotics are bacteriostatic agents that block protein synthesis in bacteria by binding to the 50S subunit of the bacterial ribosome.
  • This class of antibiotics has activity against gram-positive cocci, including streptococci and staphylococci, and some upper respiratory gram-negative bacteria, but minimal activity against enteric gram-negative rods.


  • Macrolides are commonly used to treat pharyngitis, otitis media, sinusitis, and bronchitis, especially in PCN-allergic patients, and are among the drugs of choice for treating Legionella, Chlamydia, and Mycoplasma infections. Azithromycin and clarithromycin can be used as monotherapy for outpatient community-acquired pneumonia and have a unique role in the treatment and prophylaxis against Mycobacterium avium complex (MAC) infections. Many PCN-resistant strains of pneumococci are also resistant to macrolides.
  • Clarithromycin (250–500 mg PO q12h or 1000 mg XL PO q24h) has enhanced activity against some respiratory pathogens (especially Haemophilus). It is commonly used to treat bronchitis, sinusitis, otitis media, pharyngitis, soft tissue infections, and community-acquired pneumonia. It has a prominent role in treating MAC infection and is an important component of regimens used to eradicate Helicobacter pylori (see Chapter 18, Gastrointestinal Diseases).
  • Azithromycin (500 mg PO for 1 day, then 250 mg PO q24h for 4 days; 500 mg PO q24h for 3 days; 2000-mg microspheres PO for one dose; 500 mg IV q24h) has a similar spectrum of activity as clarithromycin and is commonly used to treat bronchitis, sinusitis, otitis media, pharyngitis, soft tissue infections, and community-acquired pneumonia. It has a prominent role in MAC prophylaxis (1200 mg PO every week) and treatment (500–600 mg PO q24h) in HIV patients. It is also commonly used to treat Chlamydia trachomatis infections (1 g PO single dose). A major advantage of azithromycin is that it has much fewer drug interactions than erythromycin and clarithromycin.
  • Clindamycin (150–450 mg PO q6–8h or 600–900 mg IV q8h) is a lincosamide (related to macrolides), with activity against staphylococci and streptococci, as well as anaerobes, including B. fragilis. It has excellent oral bioavailability (90%) and penetrates well into the bone and abscess cavities. It is also used for treatment of aspiration pneumonia and lung abscesses. Clindamycin has activity against most community-associated strains of MRSA and is used for skin and soft tissue infections caused by this organism. Clindamycin may be used as a second agent in combination therapy for invasive streptococcal and clostridial infections to decrease toxin production. It may also be used for treatment of suspected anaerobic infections of the head and neck (peritonsillar or retropharyngeal abscesses, necrotizing fasciitis), although metronidazole is used more commonly for intra-abdominal infections (clindamycin has less reliable activity against B. fragilis). Clindamycin has additional uses, including treatment of babesiosis (in combination with quinine), toxoplasmosis (in combination with pyrimethamine), and Pneumocystis jirovecii pneumonia (in combination with primaquine).

Special Considerations

Adverse events: Macrolides and clindamycin are associated with nausea, abdominal cramping, and LFT abnormalities. Liver function profiles should be checked intermittently during extended therapy. Hypersensitivity reactions with prominent skin rash are more common with clindamycin, as is pseudomembranous colitis secondary to Clostridium difficile. Clarithromycin and azithromycin may cause QTc interval prolongation and myasthenia gravis exacerbations. Clarithromycin has major drug interactions caused by inhibition of the cytochrome P450 system.


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