Pharmacodynamics and bactericidal activity of gatifloxacin in experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae.
BACKGROUND
Antimicrobial resistance rates for Streptococcus pneumoniae continue to increase worldwide, and resistance to nearly every major class of antimicrobials used to treat pneumococcal infections has been reported. Gatifloxacin (GFLX) is one of the quinolones that have strong activity against S. pneumoniae.


METHODS
We compared the bacteriological, pharmacological and histopathological effects of orally administered GFLX with those of levofloxacin (LVFX) and ciprofloxacin (CPFX) in a murine model of pneumonia caused by penicillin-resistant S. pneumoniae (PRSP).


RESULTS
Treatment with GFLX resulted in a significant decrease in the number of viable bacteria (control, CPFX, LVFX, and GFLX: 6.48 +/- 0.36, 6.44 +/- 0.27, 5.51 +/- 0.15, and 4.89 +/- 0.28 log10 CFU/lung, respectively, mean +/- SD). A significant decrease in mortality was observed in the GFLX-treated group in comparison with the other groups. Histopathological examination revealed that inflammatory changes in GFLX-treated mice were less marked than in the other mice.


CONCLUSIONS
Our results suggest that orally administered GFLX is effective in PRSP pneumonia. The pharmacokinetic profiles also reflected the effectiveness of GFLX.
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. kyana-ngs@umin.ac.jp
Katsunori
K
Yanagihara
Yuichi
Y
Fukuda
Yoshitsugu
Y
Miyazaki
Kazuhiro
K
Tsukamoto
Yoichi
Y
Hirakata
Kazunori
K
Tomono
Jun-Ichi
J
Kadota
Takayoshi
T
Tashiro
Ikuo
I
Murata
Shigeru
S
Kohno
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077734:Gatifloxacin; D064704:Levofloxacin; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin