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2004
OMIG, Abstract 8
OMIG
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Is
ZymarTM (gatifloxacin 0.3%) Better Than CiloxanTM
or Fortified Tobramycin in the Treatment of Experimental Gram-Negative
Keratitis?
FS Mah, RP Kowalski, EG Romanowski, KA Yates, BR Kowalski, YJ Gordon.
The Charles T. Campbell Laboratory, University of Pittsburgh, Pittsburgh,
PA
Purpose:
To compare the efficacy of Zymar™ (gatifloxacin 0.3%), Ciloxan™
(ciprofloxacin 0.3%) and 1.4% (14 mg/ml) fortified Tobramycin (TOB)
in the treatment of experimental Gram-negative bacterial infections
of quinolone-susceptible Serratia marcescens (SM) and Pseudomonas
aeruginosa (PA) in the NZW rabbit keratitis model.
Methods: In separate but identical experiments,
done in duplicate trials, a total of 30 NZW rabbits were intrastomally
inoculated in both eyes with approximately 1,000 (1.0 x 103)
cfu/eye in 25 ul. After 16 hours, the rabbits were divided into
the 4 treatment groups (n=6 rabbits per group): 1) Zymar, 2) Ciloxan,
3) TOB and 4) saline control. One drop was instilled in both eyes
every 15 minutes for 5 doses then, every 30 minutes for 14 doses
(19 total doses over 8 hr). In addition, 6 rabbits were euthanized
at 16 hours to determine the number of corneal colony counts at
the onset of therapy. One hour after the final treatment, the animals
were euthanized and corneal colony counts determined. The first
experiment utilized a clinical isolate of SM (MICs [ug/ml]: Gat
0.125; Cip 0.047; TOB 1.5). The second experiment utilized the clinical
isolate of PA (MICs [ug/ml]: Gat 0.125; Cip 0.19; TOB 0.5).
Results: In the SM experiment, Zymar (0.8 ±
1.3) (mean ± sd Log10 cfu/ml) and Ciloxan (3.2
± 1.6) significantly decreased the number SM colony counts
compared with TOB (7.2 ± 0.6) and the saline control (7.6
± 0.6) (p = 0.000, power = 1.0). Zymar also significantly
decreased the number of SM colony counts compared with Ciloxan (p
= 0.000, power = 1.0). Zymar (-6.4 Logs) and Ciloxan (-4 Logs) decreased
colony counts compared with the onset of therapy control, whereas
TOB did not. In the PA experiment, Zymar (1.8 ± 2.1), Ciloxan
(1.7 ± 1.8), and TOB (1.8 ± 1.5) significantly decreased
the number of PA colony counts compared with the saline control
(5.3 ± 0.8) (p = 0.000, power =0.9999). There were no differences
in PA colony counts among Zymar, Ciloxan, and TOB. Zymar (-1.8 Logs),
Ciloxan (-1.9 Logs), and TOB (-1.8 Logs) decreased colony counts
compared with the onset of therapy control.
Conclusions: Only Zymar™ and Ciloxan™
were effective in reducing the number of SM corneal colony counts
in the NZW rabbit keratitis model with Zymar™ being significantly
more effective than Ciloxan™. In contrast, Zymar™, Ciloxan™,
and TOB were equally effective in reducing the number of PA corneal
colony counts in the NZW rabbit keratitis model. Zymar™ may
prove to be a valuable clinical treatment of PA and SM keratitis.
Only clinical trials can prove whether Zymar™ is an effective
treatment for PA and SM keratitis in patients.
Disclosure
code: F, C
Support: Allergan, Inc., EY08098, Eye & Ear Foundation, and
RPB
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