gemifloxacin and Chlamydia-Infections

Quinolones are currently used as empirical therapy for treatment of community-acquired lower respiratory infections as they are effective against a broad range of conventional bacterial and 'atypical' pathogens, including Chlamydia pneumoniae. C. pneumoniae is estimated to be associated with 10-20% of community-acquired pneumonia in adults, and has recently been suggested to play a role in several non-respiratory conditions, including atherosclerosis. The newer, third-generation quinolones have enhanced activity against Gram-positive bacteria, including Streptococcus pneumoniae, and prolonged serum half-lives that permit once-daily dosing. Although gemifloxacin (SB-265805) and other new quinolones have good activity against C. pneumoniae in vitro, practically all published treatment studies have relied on serological diagnosis. Consequently, the microbiological efficacy of these agents in human infection has not been assessed. This paper reviews what is known to date of the in vivo microbiological efficacy of the quinolones against C. pneumoniae, and demonstrates the importance of assessing this parameter when evaluating the clinical utility of these agents in C. pneumoniae infection.

Topics: Adult; Anti-Infective Agents; Chlamydia Infections; Chlamydophila pneumoniae; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines

Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has been implicated in the development of atherosclerosis, asthma and other chronic diseases. However, data on treatment of C. pneumoniae infections are limited. Microbiological failure of antimicrobial therapy has been described, even after prolonged courses of treatment with azithromycin, doxycycline and erythromycin. Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity against most common respiratory pathogens, including C. pneumoniae. The effect of prolonged treatment with gemifloxacin, compared with azithromycin, on viability of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C. pneumoniae by 5 log(10), which was similar to the effect of azithromycin. However, both antimicrobials failed to completely eliminate C. pneumoniae from continuously infected cells, even after 30 days of treatment. Both antibiotics decreased levels of interleukin-6 and interleukin-8 in this model, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cells, Cultured; Chlamydia Infections; Chlamydophila pneumoniae; Cytokines; Fluoroquinolones; Gemifloxacin; Humans; Interleukin-12; Interleukin-6; Interleukin-8; Naphthyridines

We compared the in vitro activity of gemifloxacin, a new quinolone antibiotic, to the activities of levofloxacin, moxifloxacin, trovafloxacin, erythromycin, and doxycycline against 20 isolates of Chlamydia pneumoniae. Gemifloxacin was the most active quinolone tested, with a MIC at which 90% of the isolates are inhibited and a minimal bactericidal concentration at which 90% of strains tested are killed of 0.25 microg/ml, but this activity was less than those of doxycycline and erythromycin.

Topics: Anti-Infective Agents; Chlamydia Infections; Chlamydophila pneumoniae; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines