Prophylactic efficacy of ophthalmic quinolones in experimental endophthalmitis in rabbits.
OBJECTIVE
The aim of this study was to determine the efficacy of 0.3% gatifloxacin ophthalmic solution in preventing bacterial endophthalmitis in rabbits.


METHODS
Eighty-four (84) albino phakic rabbits were injected unilaterally with 2 x 10(4) colony forming units of Enterococcus faecalis into the anterior chamber. The eyes received 0.3% ofloxacin ophthalmic ointment or 0.3% gatifloxacin ophthalmic solution with different regimens in three separate experiments: (1) 1 or 3 drops of gatifloxacin every 2 h or a single application of ofloxacin for 1 day; (2) 3 drops/day of gatifloxacin application started at 0, 6, and 24 h postinoculation, or 1 drop at 0 h, and 3 times daily gatifloxacin for the following 3 days; and (3) 1 or 3 drops of gatifloxacin application started at 0 h and no further application for the following 3 days. The control eyes received no treatment in the three experiments. The effectiveness of these different regimens was assessed by slit-lamp biomicroscopy and bacterial colony counts. The ocular penetration of the drugs was determined in a separate experiment, using 36 normal albino rabbits.


RESULTS
The concentration-time curves for gatifloxacin and ofloxacin appeared parallel, with mean peak concentrations of 1161 and 219 ng/mL, respectively, at 1 h postinstillation. In Experiment 1, gatifloxacin significantly reduced the inflammation and the number of living bacteria in the aqueous humor, compared with controls, whereas ofloxacin ointment did not. A single application of ofloxacin ointment was not better than 1 drop of gatifloxacin. The results of Experiment 2 showed that the effectiveness of gatifloxacin decreased as the interval between the inoculation and the onset of treatment increased. In Experiment 3, only 3 drops of gatifloxacin on day 1 kept the inflammation significantly lower than that in the control for 4 days.


CONCLUSIONS
Immediate postoperative prophylaxis would likely be effective in reducing the risk of enterococcal endophthalmitis by topical gatifloxacin.
Wada
Tomoyuki
T
Research Laboratory for Drug Development, Senju Pharmaceutical Co., Ltd., Kobe, Hyogo, Japan. tmwada@senju.co.jp
Kozai
Seiko
S
Tajika
Tetsuya
T
Sakaki
Hideyuki
H
Suzuki
Takashi
T
Ohashi
Yuichi
Y
D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D018450:Disease Progression; D009877:Endophthalmitis / Q000382:microbiology / Q000517:prevention & control*; D013293:Enterococcus faecalis; D005123:Eye / Q000378:metabolism; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077734:Gatifloxacin; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000517:prevention & control; D008297:Male; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D009824:Ointments; D009883:Ophthalmic Solutions; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009824:Ointments; D009883:Ophthalmic Solutions; D015363:Quinolones; D015242:Ofloxacin; D000077734:Gatifloxacin