Gemifloxacin: a new fluoroquinolone.
Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.
Blondeau
Joseph M
JM
Department of Microbiology, Royal University Hospital, Saskatoon, Saschatchewan, Canada. joseph.blondeau@saskatoonhealthregion.ca
Missaghi
Bayan
B
D000818:Animals; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D000077735:Gemifloxacin; D006168:Guinea Pigs; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D015337:Multicenter Studies as Topic; D009154:Mutation / Q000187:drug effects; D009287:Naphthyridines / Q000009:adverse effects / Q000138:chemical synthesis / Q000627:therapeutic use*; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic
D024841:Fluoroquinolones; D009287:Naphthyridines; D000077735:Gemifloxacin