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Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole

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


Streptococcus pneumoniae (pneumococcus) is the most commonly identified bacterial cause of pneumonia and acute sinusitis and, along with Haemophilus influenzae, is one of the two most common causes of otitis media and acute exacerbations of chronic bronchitis. The fluoroquinolones (often called quinolones) have been used widely to treat adults with these conditions. In 2016, the US Food and Drug Administration (FDA) stated that the serious adverse effects associated with fluoroquinolones generally outweigh the benefits for patients with acute sinusitis (as well as acute bronchitis and uncomplicated urinary tract infections) who have other treatment options [1]. This safety alert is likely to reduce the indiscriminate use of the fluoroquinolones, thereby preserving the susceptibility of pneumococci. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)

Doxycycline is used for the treatment of acute bacterial sinusitis (as an alternative agent for patient with penicillin allergy) [2], acute exacerbation of chronic bronchitis [3], and pneumonia in adult outpatients [4]. Trimethoprim-sulfamethoxazole (TMP-SMX) was commonly used to treat these conditions from the mid-1970s to the mid-1990s, but this combination drug has largely fallen out of favor because of the high rate of pneumococcal resistance.

Pneumococci were uniformly susceptible to all antibiotics used to treat bacterial infections of the respiratory tract until outbreaks of infection due to antibiotic-resistant pneumococci occurred in South Africa in the late 1970s [5,6]. Although the responsible organisms were called penicillin-resistant pneumococci, they had acquired genetic material that encoded broad resistance both to penicillin and to other commonly used antibiotics. In the ensuing decades, pneumococcal resistance has arisen in a number of clinically relevant classes of antibiotics.

The mechanisms of action and resistance and clinical data on the outcome of therapy in respiratory tract infections will be reviewed here for the fluoroquinolones, doxycycline, and TMP-SMX. 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 macrolides, azalides, lincosamides, and ketolides".)


The fluoroquinolones consist of a family of related compounds, including ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, and ofloxacin. Use of these drugs to treat respiratory infection represented a major therapeutic advance. At the time of their introduction, these drugs were uniformly active against S. pneumoniae as well as Haemophilus, Moraxella, Legionella, Mycoplasma, and Chlamydia spp. Except for very low rates of resistance of pneumococci and rare reports of resistance among Haemophilus, they remain so to the present. (See "Fluoroquinolones".)

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Literature review current through: Sep 2017. | This topic last updated: Jan 20, 2017.
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