The Efficacy of Intravitreal Gatifloxacin in Experimental S. epidermidis Endophthalmitis

Soo Young Lee; Eun Hye Ryu; Sun Kyung Moon; Hyun Jin Kim; So-Youn Woo; Min-Sun Cho; Hyoung Jun Koh

doi:10.3341/jkos.2008.49.4.651

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Lee, Ryu, Moon, Kim, Woo, Cho, and Koh: The Efficacy of Intravitreal Gatifloxacin in Experimental S. epidermidis Endophthalmitis

Original Article

J Korean Ophthalmol Soc 2008;49(4):651-660.

Published online: 7 September 2008

DOI: https://doi.org/10.3341/jkos.2008.49.4.651

The Efficacy of Intravitreal Gatifloxacin in Experimental S. epidermidis Endophthalmitis

Soo Young Lee, M.D.¹, Eun Hye Ryu, M.D.¹, Sun Kyung Moon, M.D.¹, Hyun Jin Kim, M.D.¹, So-Youn Woo, M.D.², Min-Sun Cho, M.D.³, Hyoung Jun Koh, M.D.⁴

¹Department of Ophthalmology, Ewha Womans University School of Medicine, Seoul, Korea

²Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea

³Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea

⁴Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea

Address reprint requests to Soo Young Lee, M.D. Department of Ophthalmology, Ewha Womans University School of Medicine, Mok-dong Hospital #911-1 Mok-dong, Yangcheon-gu, Seoul 158-710, Korea Tel: 82-2-2650-5154, Fax: 82-2-2654-4334, E-mail: sylee09@ewha.ac.kr

Received 27 June 2007 Accepted 21 November 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To compare the efficacy of intravitreal gatifloxacin with intravitreal vancomycin in the treatment of Staphylococcus epidermidis endophthalmitis in a rabbit model.

Methods

Albino rabbits (n=30), infected with an intravitreal inoculum of S. epidermidis (10⁵ colony forming unit/0.1 mL), were divided into 6 groups (n=5). Groups I and IV received 200 µg/0.1 mL of intravitreal gatifloxacin, and groups II and V were injected 1000 µg/0.1 mL of vancomycin intravitreally. Intravitreal balanced salt solutions (untreated control) were given to Groups III and VI. Intravitreal antibiotic therapy commenced 24 hours after bacterial inoculation. The bactericidal efficacy was determined by electroretinography (ERG), clinical grading, bacterial culture of vitreous aspirates and histopathologic grading. ERGs and clinical gradings were performed only for groups I, II, and III and bacterial cultures were done only for groups IV, V, and VI.

Results

Eyes in the gatifloxacin groups showed similar appearance to those in the vancomycin treated groups clinically, histologically, and functionally as proved with ERG. All aspirates from the gatifloxacin and vancomycin groups were culture‐ negative at 5 days after bacterial inoculation, whereas all eyes in the untreated control group were culture‐ positive.

Conclusions

This study demonstrated that intravitreal injection of 200 µg /0.1mL gatifloxacin appeared to be equally effective compared to intravitreal 1000 µg /0.1 mL vancomycin in the treatment of S. epidermidis endophthalmitis. If proven safe and efficacious after further study in humans, intravitreal injection of gatifloxacin could be considered an effective alternative to vancomycin for the treatment of S. epidermidis endophthalmitis.

Keywords: Endophthalmitis, Gatifloxacin, Intravitreal antibiotics, Staphylococcus epidermidis, Vancomycin

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Figure 1.

ERG responses obtained from eyes of groups I (A), II (B), and III (C). In each graph, the upper curves (wave 1) correspond to the ERG of experimental eyes and lower curves (wave 2) represent ERG from contralateral normal eyes. Baseline ERG before inoculation of S. epidermidis is on the left and the ERG of the same eyes 7 days after bacterial inoculation (6th day of antibiotics injection) is on the right. In gatifloxacin (A) and vancomycin (B) administered groups, the b‐ wave amplitude ratios (experimental/contralateral) are not changed, but b-wave implicit time ratios (experimental/contralateral) increase 7 days after bacterial inoculation. In infected control group (C), the wave of experimental eye is nearly extinguished. Short arrows, trough of a‐ waves; long arrows, peak of b-waves.

Figure 2.

Histopathologic features of the retina, ciliary body, and vitreous in three eyes from each group (H & E). Gatifloxacin (A, group I) and vancomycin (B, group II) treated eyes shows relatively clear vitreous and well preserved retinal layers. In infected control group (C, group III), the retina, ciliary body, and vitreous are infiltrated with many inflammatory cells. Left column shows the retina, choroid, and sclera. ×200 (A and B), ×100 (C). Right column represents the ciliary body and vitreous base. ×40(A, B, and C). V, vitreous cavity; R, retina; C, choroids; S, sclera; CB, ciliary body.

Figure 3.

Histopathologic features of the retina, ciliary body, and vitreous in groups 4 (A), 5 (B), and 6 (C) (H & E). Gatifloxacin (A, group IV) and vancomycin (B, group V) treated eyes show relatively clear vitreous and well preserved retinal layers. Some inflammatory cells are observed in the vitreous cavity. In untreated infected control group (C, group VI), the retina, ciliary body, and vitreous are infiltrated with dense inflammatory cells and no retinal layer is intact. Left column shows the retina, choroids, and sclera. ×200 (A and B), ×100 (C). Right column represents the ciliary body and vitreous base. ×40 (A, B, and C). V, vitreous cavity; R, retina; C, choroids; S, sclera; CB, ciliary body.

Table 1.

Grading scheme for clinical observations^*

Score	Cornea	Iris and anterior chamber	Vitreous and retina
0	Normal appearance	Normal appearance	Normal appearance
1	Mild stromal haze	Mild hyperemia, cells in anterior chamber	White condensation in vitreous, petechial hemorrhages along nerve-vessel-streaks
2	Moderate stromal haze	Moderate hyperemia, exudate in anterior chamber	Vitreous haze, optic disc and large vessels still visible
3	Cornea opaque	Iris vessels engorged and massive exudate in anterior chamber, or iris not visualizable because of anterior chamber inflammation	No red reflex

^* Cornea, iris and anterior chamber, and vitreous and retina were assigned points according to the described features. The score for anterior chamber and iris findings was multiplied by a factor of 2, and the score for vitreous findings by a factor of 3, before being added up. This score was then divided by 6 to give a range from 0 (normal appearance) to 3 (severe inflammatory changes).

Table 2.

Grading scheme for histopathologic evaluation*

Score	Cornea and limbus	Ciliary body	Vitreous base	Retina
1	Normal	Normal	Normal	Normal
2	0–1 Inflammatory cells in cornea, mild limbal infiltrate	0–50 Inflammatory cells per 40× field	0–20 Inflammatory cells per 40× field	Cystoid changes, thickness increased up to twice normal, few infiltrates
3	1–3 Corneal infiltrates, marked limbal infiltrates	50–100 Inflammatory cells per 40× field	20–50 Inflammatory cells per 40× field	Thickness increased to more than twice normal, mild infiltrate, photoreceptors recognizable
4	3–5 Infiltrates, marked limbal infiltrates	100–200 Inflammatory cells per 40× field	50–150 Inflammatory cells per 40× field	Retinal layers discernible, marked leukocytic infiltrates, no photoreceptors recognizable
5	3–5 Infiltrates, severe limbal infiltrates and swelling	>200 Inflammatory cells per 40× field	>150 Inflammatory cells per 40× field	No discernible retinal layers, massive inflammatory infiltrate

^* Cornea, ciliary body, vitreous base, and retina were assigned points according to the described features. To emphasize the importance of the findings in the posterior segment, vitreous points were multiplied by 2 and retinal points by 3. Points were added up, and the mean total score calculated. The total score was then divided by 7 to give a range from 1 (no pathologic changes) to 5 (severe inflammatory changes).

Table 3.

Statistical summary of the clinical scores and histopathologic results

Group	Clinical scores^§ at				Histopathologic scores
Group	day 2	day 3	day 4	day 7	Histopathologic scores
I, Gatifloxacin (200 µg/0.1 mL)	0.95±0.23^*	1.53±0.44^†^‡	1.92±0.18^†^‡	0.81±0.22^†^‡	1.78±0.40^†^‡
II, Vancomycin (1000 µg/0.1 mL)	1.13±0.27^*	1.37±0.42^†^‡	1.80±0.22^†^‡	0.87±0.40^†^‡	1.90±0.28^†^‡
III, Infected control (BSS 0.1 mL)	1.25±0.29	2.04±0.09	2.46±0.09	2.67±0.13	3.04±0.52

^* p>0.05, compare with infected control group (Kruskal-Wallis Test)

^† p<0.05, compare with infected control group (Kruskal-Wallis Test)

^‡ p>0.05, compare between gatifloxacin and vancomycin treated groups (Mann-Whitney U Test)

^§ Mean clinical scores are calculated on day 2, 3, 4, and 7 which corresponds to 1, 2, 3, and 6 days after bacterial inoculation, respectively.

Table 4.

Average ERG ratio^∏ of each study group

Group	Preinoculation	7 days after inoculation	p^§
I, Gatifloxacin (200 µg/0.1 mL)	1.09±0.17^*^‡	0.98±0.13^†^‡	0.116
II, Vancomycin (1000 µg/0.1 mL)	0.99±0.13^*^‡	0.90±0.36^†^‡	0.498
III, Infected control (BSS 0.1 mL)	1.07±0.11	0.29±0.15	0.068

^* p>0.05, compare with infected control group (Kruskal‐ Wallis test)

^† p<0.05, compare with infected control group (Kruskal-Wallis test); Wilcoxon signed ranks test

^Π b-wave amplitude ratio of eyes inoculated with S. epidermidis compared with contralateral control

^‡ p>0.05, compare between gatifloxacin and vancomycin treated groups (Mann-Whitney U Test)

^§ Wilcoxon signed ranks test

^∏ b-wave amplitude ratio of eyes inoculated with S. epidermidis compared with contralateral control eyes.

Table 5.

Average ERG ratio^§ of each study group

Group	Preinoculation	7 days after inoculation	p^‡
I, Gatifloxacin (200 µg/0.1 mL)	1.01±0.11^*^†	1.45±0.15^*^†	0.028
II, Vancomycin (1000 µg/0.1 mL)	1.08±0.04^*^†	1.34±0.10^*^†	0.043
III, Infected control (BSS 0.1 mL)	1.07±0.12	1.34±0.30	0.114

^* p>0.05, compare with infected congrol group (Kruskal-Wallis test)

^† p>0.05, compare between gatifloxacin and vancomycin treated groups (Mann‐ Whitney U Test)

^‡ Wilcoxon signed ranks test

^§ b-wave implicit time ratio of eyes inoculated with S. epidermidis compared with contralateral control eyes.

Table 6.

Culture results

Group	CFU/mL^‡
Group	day 3	day 4	day 6	day 8
IV, Gatifloxacin (200 µg/0.1 mL)	6586±10521.11^*^†	228±487.77^*^†	0^*^†	0^*^†
V, Vancomycin (1000 µg/0.1 mL)	65±92.33^*^†	2.0±4.47^*^†	0^*^†	0^*^†
VI, Infected control (BSS 0.1 mL)	1.25×10⁷±1.04×10⁷	7.75×10⁷±1.02×10⁷	2.75×10⁵±5.74×10⁵	2.96×10⁶±5.70×10⁶

Day 3, 4, 6, and 8 corresponds to 36 h, 3, 5, and 7 days after inoculation, respectively

^* p<0.05, compare with infected control group (Kruskal‐Wallis Test)

^† p>0.05, compare between gatifloxacin and vancomycin treated groups (Mann-Whitney U Test)

^‡ After 36 h, 3, 5, and 7 days of inoculation, vitreous aspirates were obtained and inoculated on the blood agar plate and incubated for 48 h at 37℃. After the incubation period, surface colonies were counted and converted into CFU/mL.

Table 7.

Culture results expressed as culture positivity^# and histopathologic scores

Group	No. of eyes that shows culture positive after 48 h of incubation Histopathologic
Group	day 3	day 4	day 6	day 8	Scores
IV, Gatifloxacin (200 µg/0.1 mL), N=5	4 (80%)^*^‡	2 (40%)^*^‡	0 (0%)^†^‡	0 (0%)^†^‡	2.02±0.39^§^∏
V, Vancomycin (1000 µg/0.1 mL), N=5	3 (60%)^*^‡	1 (20%)^*^‡	0 (0%)^†^‡	0 (0%)^†^‡	2.04±0.39^§^∏
VI, Infected control (BSS 0.1 mL), N=5	5 (100%)	5 (100%)	5 (100%)	4 (80%)	4.14±0.57

Day 3, 4, 6, and 8 corresponds to 36 h, 3, 5, and 7 days after inoculation, respectively

^* p>0.05, compare with infected control group (Chi-Square Test)

^† p<0.05, compare with infected control group (Chi-Square Test)

^‡ p>0.05, compare between gatifloxacin and vancomycin treated groups (Chi-Square Test)

^§ p<0.05, compare with infected control group (Kruskal-Wallis Test)

^∏ p>0.05, compare between gatifloxacin and vancomycin treated groups (Mann-Whitney U test)

^# After 36 h, 3, 5, and 7 days of inoculation, vitreous aspirates were obtained and inoculated on the blood agar plate and incubated for 48 h at 37℃. After the incubation period, number of eyes that shows culture positive are counted.

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