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Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamides, and ketolides

Daniel M Musher, MD
Section Editor
Daniel J Sexton, MD
Deputy Editor
Sheila Bond, MD


Streptococcus pneumoniae (pneumococcus), the most common cause of bacterial respiratory tract infections in children and adults, was susceptible to virtually all antibiotics used in treating such infections until outbreaks of infection due to antibiotic-resistant pneumococci were recognized in South Africa in the late 1970s [1,2]. Although the responsible organisms were called penicillin-resistant pneumococci (PRP), they had acquired genetic material that encoded resistance both to penicillin and to other commonly used antibiotics.

In the ensuing decades, resistance of pneumococci to several clinically relevant classes of antibiotics has evolved from an ominous medical curiosity to a worldwide health problem.

Macrolides, azalides, lincosamides, and ketolides are related drugs that inhibit protein synthesis at the same site in the bacterial ribosome and are generally active against the same microorganisms. Macrolides, azalides, and ketolides are (or, at least, used to be) generally active against S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella species, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Clindamycin, the only lincosamide currently in use, is effective against most pneumococci but is not active against such pathogens as H. influenzae and M. catarrhalis.

The mechanisms of action of and resistance of pneumococci to macrolides, azalides, lincosamides, and ketolides, as well as clinical data on the outcome of therapy with these drugs for otitis, sinusitis, acute exacerbations of chronic bronchitis, pneumonia, and meningitis, will be reviewed here. Resistance to the other classes of drugs is discussed separately. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole".)


The first of the macrolides, erythromycin, is poorly tolerated. After oral administration, erythromycin causes gastrointestinal distress and is not reliably absorbed; it also frequently causes thrombophlebitis after intravenous administration. As a result, erythromycin has been largely replaced by clarithromycin, a newer macrolide, and azithromycin, an azalide. It is important to note that most pneumococci that are resistant to erythromycin are also resistant to the newer macrolides and the azalides.

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Literature review current through: Nov 2017. | This topic last updated: Oct 16, 2017.
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