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

INTRODUCTION

Streptococcus pneumoniae (pneumococci) is the most common 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) are widely used to treat adults with these conditions [1-3]. Doxycycline is also recommended for the treatment of acute sinusitis [1], acute exacerbation of chronic bronchitis [4], or pneumonia in adult outpatients [2,3,5]. 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 [6,7]. Although the responsible organisms were called penicillin-resistant pneumococci (PRP), they appeared to have acquired genetic material that encoded resistance both to penicillin and to other commonly used antibiotics. In the ensuing 25 years, resistance of pneumococci to a variety of antimicrobial agents has evolved from an ominous medical curiosity to a worldwide health problem. 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, lincosamines, and ketolides".)

FLUOROQUINOLONES

The fluoroquinolones consist of a family of related compounds, including ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin. 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, Haemophilus spp, Moraxella, Legionella, Mycoplasma, and Chlamydia. Except for generally low (albeit increasing) rates of resistance to the pneumococcus and rare reports of resistance among Haemophilus, they remain so to the present. (See "Fluoroquinolones".)

Ciprofloxacin is generally thought to be less likely to cure pneumococcal infection than other quinolones, based on its minimal inhibitory concentration (MIC) against most pneumococcal strains, and the projected time to achieve serum levels that exceed the MIC. However, there are remarkable few reports of treatment failures with ciprofloxacin in the United States, although it is not regarded as a "respiratory quinolone by the Infectious Disease Society of America (IDSA) or the American Thoracic Society (ATS).
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