March 2011
Volume 52, Issue 3
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Retina  |   March 2011
Prophylactic Effect of Intravenous Moxifloxacin in a Rabbit Model of Staphylococcus epidermidis Endophthalmitis
Author Affiliations & Notes
  • Jung Yeul Kim
    From the Department of Ophthalmology and
    the Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea; and
  • Si Yeol Kim
    the Department of Ophthalmology, Kyungpook National University College of Medicine, Taegu, Republic of Korea.
  • Corresponding author: Jung Yeul Kim, Department of Ophthalmology, Chungnam National University Hospital, #640 Daesa-dong, Jung-gu, Daejeon, 301-721, Korea; kimjy@cnu.ac.kr
Investigative Ophthalmology & Visual Science March 2011, Vol.52, 1742-1747. doi:10.1167/iovs.10-5231
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      Jung Yeul Kim, Si Yeol Kim; Prophylactic Effect of Intravenous Moxifloxacin in a Rabbit Model of Staphylococcus epidermidis Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2011;52(3):1742-1747. doi: 10.1167/iovs.10-5231.

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Abstract

Purpose.: To compare the prophylactic effects of intravenous moxifloxacin and vancomycin for Staphylococcus epidermidis endophthalmitis in a rabbit model.

Methods.: Albino rabbits (n = 60) were divided into three groups. Intravenous moxifloxacin was injected into 20 animals (group 1), and intravenous vancomycin was injected into 20 animals (group 2). In group 3, 20 animals received 0.9% normal saline. After these prophylactic intravenous injections, the right eyes of the 60 rabbits were injected intravitreally with 105 colony-forming units of S. epidermidis. Intravenous antibiotic injection was repeated on days 1, 2, and 3 after infection. Clinical features were evaluated on days 1, 3, 5, and 7 after infection, and 10 eyes per group were then enucleated for histopathologic examination. Vitreous aspirates were obtained for bacterial culture on days 1, 3, 5, and 7 after infection from the other 10 eyes per group.

Results.: The moxifloxacin group showed significant clinical effects at days 1, 3, 5, and 7 (P = 0.019, < 0.001, < 0.001, and < 0.001, respectively); bacteriologic results at days 1, 3, 5, and 7 (P = 0.001, 0.002, 0.01, and 0.002, respectively); and histopathologic results, with less severe inflammation and relatively well-preserved retinal architecture. However, no difference was detected between the vancomycin group and control group in any aspect examined.

Conclusions.: Intravenously administered moxifloxacin showed a significant prophylactic effect against S. epidermidis endophthalmitis. Thus, intravenous moxifloxacin may be a useful prophylactic medication against postoperative endophthalmitis.

Bacterial endophthalmitis occurring after intraocular surgery is a major complication that can cause vision loss. According to the Endophthalmitis Vitrectomy Study (EVS), in patients with bacterial endophthalmitis who had light perception at the time of admission, only 33% of eyes had a final visual acuity of 20/40, despite adequate treatment. Of patients in whom the visual acuity was better than light perception at the time of admission, more than 60% of eyes had a final visual acuity of 20/40 or better with the same protocol. 1 Reasons for such a poor prognosis in patients with bacterial endophthalmitis may include toxic substances generated before the death of the bacteria and host immune reactions, causing damage to intraocular tissue, the retina in particular, although bacteria were effectively removed by immediate treatment after the diagnosis. 2,3  
The causative bacteria of endophthalmitis primarily include the normal flora present on the conjunctiva and eyelid. 4 The proportion of Gram-positive pathogens is 94.2%. Of these, Staphylococcus epidermidis is the most common, followed by Staphylococcus aureus. Some cases have been reported in which the causative bacterium is a Gram-negative pathogen. Of these, Proteus mirabilis was the most common, but its proportion was only 5.9%. 5  
Presently, treatment regimens recommended for bacterial endophthalmitis include intravitreal injection of antibiotics, for which a combination of vancomycin and ceftazidime or vancomycin and amikacin have frequently been used. 6 The combined use of these antibiotics is effective for the treatment of most of the bacteria triggering endophthalmitis. Intravitreal injection of these antibiotics is effective in promptly achieving a high therapeutic concentration, 6 but sufficient antibiotic levels in the vitreous may be present for only a limited time after such an injection. In inflamed eyes, in particular, antibiotic levels can decrease quickly because of the breakdown of the blood–retina barrier and consequent enhanced clearance. After an intravitreal injection of antibiotics, complications such as retinal detachment or vitreous hemorrhage can occur. Particularly in the case of amikacin, retinal toxicity has been documented. 6  
To prevent ocular damage due to endophthalmitis, regulation of host immune responses to various molecules produced by bacteria and bacterial eradication are both important. To accomplish this, combined therapy with an antibiotic and a steroid could also be applied. However, in cases in which active bacteria remain, use of a steroid can further aggravate the infection. 7  
Systemic antibiotic therapy can avoid the occurrence of local complications, such as retinal detachment, vitreal hemorrhage, and retinal toxicity, that may occur after an intravitreal injection. Because of the longer half-life of these antibiotics, they advantageously maintain therapeutic concentrations for a longer time. 6 We anticipated that bacteria could be eradicated effectively and promptly in cases in which the antibiotics are present at a concentration higher than the therapeutic level at the time point when the bacteria invade the eye. Because of this, any inflammatory response to toxins produced by the bacteria should also be minimized. 
Moxifloxacin is a recently introduced fourth-generation fluoroquinolone antibiotic. After intravenous administration of moxifloxacin, a high degree of intravitreal penetration occurs. 8,9 Accordingly, in response to most of the bacteria triggering bacterial endophthalmitis after surgery, including S. epidermidis, the concentration has been reported to be higher than the minimum inhibitory concentration of isolates. 8  
Recently, moxifloxacin has been extensively applied via various routes of administration, such as eye drops, 10 the oral route, 11 and intravenous injection. 11 To our knowledge, however, there is no reported study on the prophylactic effect of systemic moxifloxacin on endophthalmitis after surgery. 
The objective of the present study was to examine whether an intravenous injection of moxifloxacin could effectively remove bacteria in an experimental model of S. epidermidis endophthalmitis. Although bacteria are effectively removed when antibiotics are used after the occurrence of infections, the severe clinical manifestations and retinal tissue injury may be caused by inflammatory reactions to toxins produced by the bacteria. Accordingly, we also examined the prophylactic effect of an intravenous injection of moxifloxacin in the aspects of the clinical manifestations and tissue injury. 
Materials and Methods
Strains
Commercially available S. epidermidis (ATCC 12228; ATTC, Manassas, VA), sensitive to moxifloxacin and vancomycin, was used. The minimum inhibitory concentration of 90% of the isolates (MIC90) of moxifloxacin and vancomycin against the pathogens was 0.13 and 1.9 μg/mL, respectively. S. epidermidis was diluted with balanced salt solution, and the sample was prepared to make a final concentration of 106 colony-forming units (CFU)/mL. Then, an intravitreal injection of the samples was made at a volume of 0.1 mL (105 CFU) in rabbits. 
Animals
The rabbits were treated based on the guidelines proposed in the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. New Zealand albino rabbits weighing 2 to 2.5 kg were used. For anesthesia, an intramuscular injection of xylazine hydrochloride (2 mg/kg) and tiletamine hydrochloride/zolazepam hydrochloride (1.5 mg/kg) was performed before the intraocular inoculation of the bacteria. An intravitreal injection, a vitreous aspiration, and a fundus examination were performed after mydriasis with topically applied 0.5% tropicamide/0.5% phenylephrine hydrochloride. 
Experimental Infection
Immediately before an intraocular injection of S. epidermidis, an anterior chamber paracentesis was performed. A 0.1-mL aqueous aspirate was taken to prevent elevating the intraocular pressure. An intravitreous injection of S. epidermidis was performed at a concentration of 105 CFU/0.1 mL via the pars plana. The intravitreal injection was achieved by using a tuberculin syringe with a 26-gauge needle under ophthalmoscopic examination to ensure that the needle was inserted in the midvitreous cavity of the vitreal cavity, such that the bevel was placed toward the anterior direction; the bacteria were then inoculated. The experimental infection of S. epidermidis was performed only in the right eye. 
Study Groups
At 2 hours before the intravitreal injection of S. epidermidis, in the experimental groups, but not the control group, an intravenous injection of the antibiotics was performed via a marginal ear vein. In the current experiment, 60 rabbits were randomly assigned to three groups. In group 1, an intravenous injection of moxifloxacin (20 mg/kg) was performed 2 hours before the induction of S. epidermidis endophthalmitis. After this, on days 1, 2, and 3 (24, 48, and 72 hours after the prophylactic intravenous injection), an intravenous moxifloxacin injection was performed once daily. In group 2, at 2 hours before the induction of S. epidermidis endophthalmitis, an intravenous injection of vancomycin (50 mg/kg) was made. From 12 hours after this prophylactic antibiotics injection, an intravenous injection of vancomycin was initiated twice daily on days 1, 2, and 3. In group 3 (control), an intravenous injection a 0.9% normal saline was performed once at 2 hours before the induction of the experimental endophthalmitis and on days 1, 2, and 3 after the induction of endophthalmitis. The doses of antibiotics used in groups 1 (moxifloxacin) and 2 (vancomycin) were equivalent to those at which the therapeutic concentration can be achieved in human subjects—respectively, 400 mg/once daily and 1 g twice daily. 12,13  
In 10 rabbits per group which were randomly selected, the clinical features were examined on days 1, 3, 5, and 7 after the inoculation of bacteria by a single masked observer. On day 7, after the final clinical examination was performed, the animals were killed by intracardiac injection of pentobarbital sodium 500 mg. In these rabbits, an enucleation of the right eye was performed, followed by a histopathologic examination. In the other 10 rabbits per group, on days 1, 3, 5, and 7 after the intravitreal injection of the bacteria, the vitreous body was aspirated with a 26-gauge tuberculin syringe via the pars plana, at a volume of 0.1 mL. Then, a microbiologic examination was performed. 
Clinical Observations
After the induction of S. epidermidis endophthalmitis, on days 1, 3, 5, and 7, a slit lamp examination and an indirect ophthalmoscopic examination were performed. An independent, masked observer who was unaware of the purposes of the study scored the ocular findings on a numeric scale based on criteria proposed by Peyman et al., 14 (Table 1), and the total scores were compared. 
Table 1.
 
Clinical Grading Scale
Table 1.
 
Clinical Grading Scale
Score Conjunctiva Cornea Iris Vitreous Body
0 Normal Clear Normal Clear
1 Mild edema Focal edema Mild hyperemia Areas of vitreous haze, some fundus details visible, good red reflex
2 Edema, mild hyperemia, slight exudate Diffuse edema Marked hyperemia Moderate vitreous haze, fundus details not clear, partial red reflex
3 Edema, mild hyperemia, heavy exudate Opaque Marked hyperemia, engorged vessels, synechia, irregular pupil No red reflex
Histopathology
On day 7 after the induction of S. epidermidis endophthalmitis, the final clinical examination was performed, and the animals were euthanatized. In each rabbit, the right eyeball was enucleated and fixed in formalin solution. A paraffin-embedded block was prepared and sectioned at 2 to 3 μm. Sections were stained with hematoxylin and eosin and examined by an experienced ocular pathologist in a masked fashion. 
Bacterial Quantification
In each group, in the remaining 10 rabbits, the 0.1-mL vitreous body was aspirated. The sample was then homogenized and serially diluted with balanced salt solution, and 10-μL aliquots of these dilutions were placed on blood agar in triplicate. After incubation at 36°C for 48 hours, the colonies were counted, and the concentration of the initial sample was calculated. 
Statistical Analyses
Statistical analyses were performed to examine differences between the three groups by using the Kruskal-Wallis test. A paired comparison was made to identify statistical significance by using the Mann-Whitney U test. P < 0.05 was deemed to indicate statistical significance. 
Results
Clinical Examination
On days 1, 3, 5, and 7 after the intravitreous injection of S. epidermidis, significant differences were observed in clinical manifestations among the three groups. In the moxifloxacin group, on days 1, 3, 5, and 7, mean scores were approximately 1 point. In each rabbit, clinical signs were mild or absent. In the vancomycin and control groups, however, as time elapsed after the induction of experimental endophthalmitis, the clinical manifestations became aggravated. All the animals showed signs of the inflammation. Significant differences were observed between the moxifloxacin and vancomycin groups and between the moxifloxacin and control groups; no significant difference was seen between the vancomycin and control groups (Table 2, Fig. 1). 
Table 2.
 
Clinical Scores in the Three Groups
Table 2.
 
Clinical Scores in the Three Groups
Moxifloxacin Vancomycin Control P *
Day 1 1.1 ± 0.99 2.2 ± 0.92 2.4 ± 0.97 0.019
Day 3 1.8 ± 0.92 3.6 ± 0.84 4.2 ± 1.32 <0.001
Day 5 1.2 ± 1.03 5.5 ± 1.35 5.7 ± 1.42 <0.001
Day 7 0.5 ± 0.71 6.7 ± 1.77 6.9 ± 1.85 <0.001
Figure 1.
 
(AC) External photographs. (DF) B-scan images of rabbit eyes at 7 days after infection with S. epidermidis. (A, D) Group 1, the moxifloxacin injection group; (B, E) group 2, the vancomycin injection group; and (C, F) group 3, the control group.
Figure 1.
 
(AC) External photographs. (DF) B-scan images of rabbit eyes at 7 days after infection with S. epidermidis. (A, D) Group 1, the moxifloxacin injection group; (B, E) group 2, the vancomycin injection group; and (C, F) group 3, the control group.
Histologic Examination
On day 7 after the induction of S. epidermidis endophthalmitis, an enucleation was performed after the final clinical examination. The enucleated eyeballs were referred to the department of histopathology for examination. In the moxifloxacin group, a small number of inflammatory cells had infiltrated the ganglion cell layer, or only slight loss of ganglion cells had occurred. There were no other notable findings. In all 10 rabbits, the architecture of the retina was well maintained. The vancomycin group and the normal saline/control group showed moderately severe inflammatory cell infiltrations. Destruction of the normal retinal architecture was seen in the inner or outer layer of the retina or across all layers of the retina (Fig. 2). 
Figure 2.
 
High-power photomicrographs of rabbit eyes at day 7 after infection with S. epidermidis. (A) Group 1, the moxifloxacin injection group; (B) group 2, the vancomycin injection group; and (C) group 3, the control group. (A) Nuclear pyknosis and cell loss were noted in the ganglion cell layer, with relatively well-preserved retinal architecture. (B, C) Intraretinal damage was relatively limited to the inner retinal layers in the top images, whereas the bottom images showed more severe inflammation, with no discernible retinal layers (H&E staining; magnification, ×200).
Figure 2.
 
High-power photomicrographs of rabbit eyes at day 7 after infection with S. epidermidis. (A) Group 1, the moxifloxacin injection group; (B) group 2, the vancomycin injection group; and (C) group 3, the control group. (A) Nuclear pyknosis and cell loss were noted in the ganglion cell layer, with relatively well-preserved retinal architecture. (B, C) Intraretinal damage was relatively limited to the inner retinal layers in the top images, whereas the bottom images showed more severe inflammation, with no discernible retinal layers (H&E staining; magnification, ×200).
Microbiologic Results
On days 1, 3, 5, and 7 after the intravitreal injection of S. epidermidis, the bacterium was identified from the vitreous body obtained via the pars plana. In no case was a bacterium other than S. epidermidis identified. In all three groups, the greatest number of S. epidermidis was detected on day 1. Thereafter, a decreasing trend was noted. Particularly in group 1 treated with injected moxifloxacin, no bacteria were seen in any of the 10 animals in the vitreous body obtained on days 5 and 7. In the vancomycin and control groups, bacteria continued to be detected. On days 5 and 7, however, the number of detected bacteria had greatly decreased; no bacteria were detected in two cases and one case, respectively. On days 1, 3, 5, and 7 after an intravitreous injection of S. epidermidis, a bacterial culture test showed significant differences among the three groups. Significant differences were observed between the moxifloxacin and vancomycin groups and between the moxifloxacin and control groups; however, no significant difference was seen between the vancomycin and control groups (Table 3). 
Table 3.
 
Bacteriological Findings in the Three Groups
Table 3.
 
Bacteriological Findings in the Three Groups
Moxifloxacin Vancomycin Control P *
Day 1 3.2 × 102 (0–1.5 × 103) 5.4 × 106 (7.2 × 105–1.5 × 107) 1.8 × 107 (1.7 × 106–3.5 × 107) 0.001
Day 3 4.3 × 10 (0–6.2 × 102) 5.7 × 105 (4.7 × 104–2.2 × 106) 2.3 × 106 (1.1 × 104–6.2 × 106) 0.002
Day 5 0 (0) 8.2 × 103 (0–3.1 × 104) 7.4 × 105 (0–2.1 × 106) 0.01
Day 7 0 (0) 1.8 × 103 (0–2.4 × 104) 6.7 × 103 (0–1.8 × 104) 0.002
Discussion
The postoperative occurrence of endophthalmitis has been reported to have an incidence of 0.05% to 0.37%, 15 17 and it has been reported to increasingly occur after surgeries such as sutureless cataract operations, vitreous surgery, secondary intraocular lens implantation, and penetrating keratoplasty. 2 Previously, povidone iodine was reported to be the only regimen with a prophylactic effect on the postoperative occurrence of endophthalmitis. 18 All other reported prophylactic interventions, subconjunctival antibiotic injection, preoperative lash trimming, preoperative saline irrigation, preoperative topical antibiotics, antibiotics-containing irrigating solutions, and the use of intraoperative heparin, have been ineffective. 18  
To date, no guidelines have been established regarding the prophylactic use of antibiotics before intraocular surgery. However, many ophthalmologists do use antibiotics, systemically or by topical application. 6,19 However, the degree of accessibility to the vitreous cavity has been reported to be very low; therefore the degree of effect against endophthalmitis should also be very low. 14,20 28  
Most cases of endophthalmitis involve Gram-positive bacteria, 5,29 and vancomycin has a broad spectrum of activity against Gram-positive bacteria. Accordingly, in cases of bacterial endophthalmitis, it is widely used as a selective treatment agent for intraocular injections. 5,17,29,30 The intravenous injection of antibiotics such as vancomycin has been the conventional treatment modality in cases of bacterial endophthalmitis. 30,31 According to the Endophthalmitis Vitrectomy Study (EVS), however, intravenous administration of the antibiotics was not effective in treating endophthalmitis. 29 According to Ferencz et al., 32 after an analysis of the concentration in the vitreous cavity after vancomycin was administered via the intravenous and intravitreous routes in patients who postoperatively developed endophthalmitis, an intravenous injection did not reach a therapeutic concentration, in contrast to the intravitreous one. 
Moxifloxacin is a fourth-generation quinolone antibiotic and has a broad spectrum of antibacterial activity. After U.S. Food and Drug Administration (FDA) approval, it has been widely used topically or by intravitreous injection or oral administration and as an intravenous injection. 12 Gao et al. 33 showed that moxifloxacin did not display retinal toxicity when the intravitreal concentration was 150 μg/mL in rabbits. In general, compared with other antibiotics, the incidence of side effects was relatively low. After systemic administration, mild side effects, such as gastrointestinal distress, dizziness, or skin rashes, may be seen in 4% to 8% of cases. 8 After systemic administration, the amount reaching the intravitreous cavity has been found to be relatively greater than most antibiotics, perhaps because moxifloxacin can permeate the blood–retinal barrier due to its lipophilic nature and low molecular weight. 34 The intravitreous concentration exceeds the minimum inhibition concentration of most bacteria that cause endophthalmitis. 8 According to results of experiments conducted in human subjects and rabbits, the maximum concentration within the intravitreous cavity was confirmed to be reached 2 hours after an intravenous injection. 12 In addition, in experiments performed in rabbits, until at least 5 hours later, the intravitreous concentration was maintained at a concentration higher than the therapeutic concentration. 12 Rabbits have a metabolic profile comparable to that of humans. Considering that a half-life of the drugs administered to rabbits was shorter than in humans by 5 to 10 times, 35 the intravitreous concentration of moxifloxacin would be expected to be maintained at a therapeutic level for more than 24 hours in humans. The current therapeutic dose of moxifloxacin approved by the FDA is 400 mg once a day. This dose had areas under the vitreous and serum curves (AUC) almost identical to those in cases in which a dose of 20 mg/kg was injected in rabbits, as shown in the present study. 12  
Meredith et al. 36 created an experimental model of S. epidermidis endophthalmitis and confirmed that the clinical manifestations varied, depending on the number of bacteria injected. In cases in which an intravitreous injection of a small number of bacteria was performed, the bacteria detected gradually decreased, even with no treatment. This eventually led to an aseptic state and the clinical characteristics spontaneously healed. This spontaneous sterilization was consistent with the reports of Meyers-Elliott and Dethlefs 37 and Smith et al. 38 Little is known about the mechanism. According to bacterial proliferation in the restricted space of the vitreous cavity, however, the changes in the composition of the vitreous body, such as the depletion of nutrients and oxygen, the accumulation of secretory materials, and the accumulation of antibacterial substances and inflammatory cells, may be responsible. However, in cases in which more than 105 bacteria were infused, the number of bacteria detected during a period ranging from days 1 to 2 began to decrease. The clinical characteristics, however, were shown to be aggravated during the period ranging from days 6 to 7. 36 Similar findings were reported by Meyers-Elliott and Dethlefs. 37  
In the present study, based on these previous reports, in determining whether the antibiotic treatments could cause the changes in the clinical characteristics, we ruled out the possibility that the clinical characteristics resolved spontaneously by setting the bacterial inoculum at 105 CFU/0.1 mL. In all three groups, the number of bacteria detected was the greatest on day 1. On day 3, it had decreased. In a manner similar to that in previous reports, the number of detectable bacteria decreased within 3 days. In the moxifloxacin group, on days 1 and 3 after the induction of experimental endophthalmitis, the number of detectable bacteria was significantly smaller than in the other two groups. On days 5 and 7, no bacteria were detected in any of the rabbits. In the group in which vancomycin was administered and in the control group, cases were seen in which no bacteria were detected on day 5 (2 and 1 rabbit(s), respectively). Clinical characteristics were mild on days 1 and 3 in the moxifloxacin group compared with the other two groups, and from day 3 on, the symptoms further improved. In contrast, in the vancomycin and control groups, clinical characteristics were severe and the clinical course became further aggravated. Accordingly, despite the possibility of spontaneous sterilization, in cases in which moxifloxacin was administered, the effects in eradicating bacteria were significantly better than in the group in which vancomycin was administered and in the control group. Clinical characteristics did not spontaneously improve; they improved because of the effects of moxifloxacin. 
In the present study, the clinical characteristics and the results of the histopathologic analysis in the moxifloxacin group showed significantly better outcomes than the other groups. A possible mechanism might be as follows. First, the prophylactic use of moxifloxacin could reduce the time during which the bacteria proliferate and then release toxic materials, which may lead to a shortened time for inducing host immune responses. Second, this phenomenon may be due to the unique characteristics of moxifloxacin. Unlike other types of β-lactam antibiotics and vancomycin, which block cell wall synthesis, moxifloxacin blocks DNA synthesis, leading to its antibacterial effects. Accordingly, this can reduce the tissue damage and inflammation by reducing the release of proinflammatory bacterial protein toxins during antibiotic killing. 12 Moxifloxacin has also been reported to suppress the release of interleukin-1α and tumor necrosis factor-α in human monocytes; thus, it has immunomodulatory properties. 39  
This was a double-masked randomized placebo-controlled investigation in which we randomly assigned 60 rabbits to three groups with different intravenous therapies. Twenty rabbits in each group were randomly divided into two subgroups: One subgroup of 10 rabbits was used in the clinical examination and the other 10 rabbits were used in bacteriologic and histopathologic examinations. Each examiner who participated in group assignments, bacteriology, and clinical scoring was masked to the result. However, there are limitations in this study which must be acknowledged. First, although it was double masked and each examination was performed by an experienced examiner, the same examiner was assigned to perform bacteriology and the clinical examination in each examination. Therefore, the possibility that intra- or interexaminer bias might affect the results cannot be excluded. Second, even though the samples were divided randomly, the number in the comparative groups was small. The sample showing extreme clinical symptoms or pathologic change could have been assigned to one group in the process of dividing into subgroups, and that might have also had an effect on the result. However, the clinical examination in three subgroups of three groups with different treatment options showed a statistically significant difference in the result. If the two subgroups that received the same treatment option showed a significantly different result in infection and inflammation, it can be anticipated that clinical examination and bacteriology will have a different result as well. Further larger-scale prospective studies are warranted to examine whether intravenous moxifloxacin is safe and effective in suppressing the postoperative occurrence of endophthalmitis in patients who undergo intraocular surgery. 
In conclusion, in our study, intravenous moxifloxacin was effective in preventing the occurrence of experimental S. epidermidis endophthalmitis. To date, no guidelines have been established regarding the prophylactic use of antibiotics in cases of postoperative bacterial endophthalmitis. In the present study, to induce experimental endophthalmitis, a sufficiently large amount of S. epidermidis bacteria (105 CFU) was intravitreously administered, and the dose of moxifloxacin administered to the rabbits was approximately equivalent to the AUC corresponding to the therapeutic dose currently used in humans. Therefore, equivalent or more potent effects are expected to occur in S. epidermidis bacterial endophthalmitis after surgery in humans. 
Footnotes
 Disclosure: J.Y. Kim, None; S.Y. Kim, None
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Figure 1.
 
(AC) External photographs. (DF) B-scan images of rabbit eyes at 7 days after infection with S. epidermidis. (A, D) Group 1, the moxifloxacin injection group; (B, E) group 2, the vancomycin injection group; and (C, F) group 3, the control group.
Figure 1.
 
(AC) External photographs. (DF) B-scan images of rabbit eyes at 7 days after infection with S. epidermidis. (A, D) Group 1, the moxifloxacin injection group; (B, E) group 2, the vancomycin injection group; and (C, F) group 3, the control group.
Figure 2.
 
High-power photomicrographs of rabbit eyes at day 7 after infection with S. epidermidis. (A) Group 1, the moxifloxacin injection group; (B) group 2, the vancomycin injection group; and (C) group 3, the control group. (A) Nuclear pyknosis and cell loss were noted in the ganglion cell layer, with relatively well-preserved retinal architecture. (B, C) Intraretinal damage was relatively limited to the inner retinal layers in the top images, whereas the bottom images showed more severe inflammation, with no discernible retinal layers (H&E staining; magnification, ×200).
Figure 2.
 
High-power photomicrographs of rabbit eyes at day 7 after infection with S. epidermidis. (A) Group 1, the moxifloxacin injection group; (B) group 2, the vancomycin injection group; and (C) group 3, the control group. (A) Nuclear pyknosis and cell loss were noted in the ganglion cell layer, with relatively well-preserved retinal architecture. (B, C) Intraretinal damage was relatively limited to the inner retinal layers in the top images, whereas the bottom images showed more severe inflammation, with no discernible retinal layers (H&E staining; magnification, ×200).
Table 1.
 
Clinical Grading Scale
Table 1.
 
Clinical Grading Scale
Score Conjunctiva Cornea Iris Vitreous Body
0 Normal Clear Normal Clear
1 Mild edema Focal edema Mild hyperemia Areas of vitreous haze, some fundus details visible, good red reflex
2 Edema, mild hyperemia, slight exudate Diffuse edema Marked hyperemia Moderate vitreous haze, fundus details not clear, partial red reflex
3 Edema, mild hyperemia, heavy exudate Opaque Marked hyperemia, engorged vessels, synechia, irregular pupil No red reflex
Table 2.
 
Clinical Scores in the Three Groups
Table 2.
 
Clinical Scores in the Three Groups
Moxifloxacin Vancomycin Control P *
Day 1 1.1 ± 0.99 2.2 ± 0.92 2.4 ± 0.97 0.019
Day 3 1.8 ± 0.92 3.6 ± 0.84 4.2 ± 1.32 <0.001
Day 5 1.2 ± 1.03 5.5 ± 1.35 5.7 ± 1.42 <0.001
Day 7 0.5 ± 0.71 6.7 ± 1.77 6.9 ± 1.85 <0.001
Table 3.
 
Bacteriological Findings in the Three Groups
Table 3.
 
Bacteriological Findings in the Three Groups
Moxifloxacin Vancomycin Control P *
Day 1 3.2 × 102 (0–1.5 × 103) 5.4 × 106 (7.2 × 105–1.5 × 107) 1.8 × 107 (1.7 × 106–3.5 × 107) 0.001
Day 3 4.3 × 10 (0–6.2 × 102) 5.7 × 105 (4.7 × 104–2.2 × 106) 2.3 × 106 (1.1 × 104–6.2 × 106) 0.002
Day 5 0 (0) 8.2 × 103 (0–3.1 × 104) 7.4 × 105 (0–2.1 × 106) 0.01
Day 7 0 (0) 1.8 × 103 (0–2.4 × 104) 6.7 × 103 (0–1.8 × 104) 0.002
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