Intravitreal taurolidine against experimental Staphylococcus epidermidis endophthalmitis in rabbits

PURPOSE: Taurolidine is a broad spectrum, non-antibiotic antimicrobial agent, not previously tested against infectious endophthalmitis. The efficacy of intravitreal taurolidine in the treatment of experimental Staphylococcus epidermidis endophthalmitis was evaluated and compared with vancomycin in a rabbit model. METHODS: The right eyes of 34 albino rabbits were infected with an intravitreal inoculum of S. epidermidis (10(5) colony-forming units/0.1 ml). The right eyes of four rabbits (group 7) were not infected and served as uninfected controls. 24 hours after inoculation of bacteria the animals were divided into the following treatment groups: group 1 (7 rabbits) received intravitreal taurolidine at 24 hours and group 2 (7 rabbits) received at 48 hours. Group 3 (7 rabbits) received vancomycin at 24 hours and group 4 (7 rabbits) at 48 hours. Group 5 (3 rabbits) received polyvinylpyrrolidone at 24 hours and group 6 (3 rabbits) at 48 hours. Clinical scoring was performed at 24, 48 and 72 hours. At 72 hours post inoculation, vitreous samples were collected for quantitative microbiological studies and then, the eyes were enucleated for histopathological scorings. RESULTS: The clinical and histopathological examinations revealed significant amelioration of inflammation in eyes treated with taurolidine and vancomycin when compared with polyvinylpyrrolidone. The eyes treated with taurolidine also had significantly lower colony forming units than the eyes treated with polyvinylpyrrolidone and taurolidine rendered many eyes sterile. CONCLUSION: Taurolidine is expected to be a potential agent for treatment of S. epidermidis endophthalmitis.     

Spontaneous sterilization in experimental Staphylococcus epidermidis endophthalmitis

We created a standardized model of endophthalmitis in the aphakic rabbit eye using a laboratory strain of Staphylococcus epidermidis of known characteristics (ATCC 155). Eyes were injected with the following number of organisms: 170, 3760, 8750, 170,000 and 460,000. Serial quantitative cultures, clinical grading of infection and histopathologic studies were performed on days 1, 2, 3, 7 and 14. Bacteria appeared to multiply rapidly during the first 24 hr with peak recovery at 8 to 24 hr. Fewer bacteria were cultured on the third day after injection, and positive cultures were rare after the third day. Inflammatory scores were initially higher with each increased number of injected bacteria and tended to increase for the first 3 to 5 days.     

Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin

Endophthalmitis remains a dreaded complication of intraocular surgery and penetrating eye trauma. Subconjunctival, topical, and systemic antibiotics have been largely ineffective in the treatment of endophthalmitis, whereas intravitreal antibiotics have proved efficacious. Methicillin-resistant Staphylococcus epidermidis has become an important pathogen in many infections, including endophthalmitis. Toxicity, clearance, and efficacy of intravitreal vancomycin were evaluated in the treatment of experimental methicillin-resistant S. epidermidis endophthalmitis. No evidence of retinal toxicity was found and therapeutic levels were demonstrated six days after injection. The treated rabbit eyes showed a marked beneficial effect when compared to the untreated eyes. If experience confirms the safety of intravitreal vancomycin in human eyes, vancomycin should be considered the drug of choice for methicillin-resistant S. epidermidis endophthalmitis.     

兔玻璃体腔注射美罗培南治疗细菌性眼内炎

目的评价兔玻璃体腔注射国产美罗培南对敏感菌引起的眼内炎的疗效。方法选取健康成年日本大耳白兔24只，随机分为Ⅰ、Ⅱ两组，每组12只，分别玻璃体腔内接种金黄色葡萄球菌和绿脓杆菌建立相应的眼内炎模型。待出现典型眼内炎体征时，Ⅰ组和Ⅱ组再随机分为A、B组和C、D组。B、D组玻璃体腔均注射美罗培南1．25mg，A、C组分别注射万古霉素1．0mg和复达欣2．0mg作为对照。通过临床炎症评分、细菌培养阳性率、组织学检查病理评分等指标评估药物疗效。结果在两种眼内炎模型中，美罗培南用药后临床炎症评分均有显著下降，用药前后相比有统计学差异，但与万古霉素、复达欣相比无统计学差异；美罗培南用药后细菌培养阳性率在金黄色葡萄球菌和绿脓杆菌眼内炎模型中分别为0和16．7％，均低于万古霉素和复达欣，与万古霉素相比差异有统计学意义；用药2周后组织学检查显示绝大多数标本视网膜组织结构基本完整，层间有不同程度变性和坏死伴炎症细胞浸润，美罗培南与万古霉素、复达欣相比其视网膜病理评分均无统计学差异。结论兔玻璃体腔注射美罗培南治疗敏感金黄色葡萄球菌和绿脓杆菌引起的眼内炎，疗效分别与万古霉素、复达欣基本相当，但当眼内炎体征已明显时单次眼内用药很难完全控制炎症。     

Intravitreal cephalothin in experimental staphylococcal endophthalmitis

Intravitreal cephalothin was used to treat experimentally induced bacterial endophthalmitis in rabbit eyes. A dose of 2 mg and less was apparently nontoxic to all intraocular structures. Thirty-two hours after injection of a 2 mg dose, the level remaining in the vitreous was above the minimal inhibitory concentration for most susceptible organisms. Treatment of experimentally induced staphylococcal infections of the vitreous was successful with early intravitreal injection. When therapy was delayed, vitreous bands and posterior lens cataracts developed. Eyes of control animals receiving intramuscular and subconjunctival injections of cephalothin all progressed to phthisis bulbi.     

Intravitreal oxacillin in experimental staphylococcal endophthalmitis

Summary We compared combined intravitreal and systemic oxacillin to combined subconjunctival and systemic oxacillin in the treatment of experimental staphylococcal endophthalmitis. Intravitreal injection of 500 mcg was nontoxic to all intraocular structures and produced concentrations in the vitreous bactericidal to all susceptible strains of Staphylococcus aureus for almost 24 hours. In eyes treated 8, 10, and 12 hours after intravitreal inoculation of 10000 to 20000 penicillinase-producing S. aureus organisms, intravitreal injection of 500 mcg of oxacillin was superior to subconjunctival injection of 100 mg when each was combined with seven days of intensive intramuscular oxacillin.

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Zusammenfassung Zur Behandlung einer experimentellen Staphylokokken-Endophthalmitis wurde eine Kombination von intravitrealem und intramuskulärem Oxacillin mit einer Behandlung, bei der subkonjunctivale mit intramuskulären Injektionen von Oxacillin kombiniert wurden, verglichen. Die Injektion von 500 g in den Glaskörper verursachte keinen intraokulären Schaden und erzeugte eine Glaskörperkonzentration, die für fast 24 Std die empfindlichen Kolonien des Staphylococcus aureus töten konnte. Penicillinase produzierender Staphylococcus aureus (10000–20000 Organismen) wurde in den Glaskörper injiziert. Die Augen wurden dann nach 8,10 und 12 Std behandelt. Eine Injektion von 500 g Oxacillin in den Glaskörper war erfolgreicher als eine Injektion von 100 mg unter die Bindehaut, wenn beide Methoden mit einer 7 Tage währenden intramuskulären Oxacillin-Therapie verbunden waren.

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This study was supported in part by Public Health Service grant 1107-03 and Illinois Lions Club.     

The efficacy of intravitreal levofloxacin and intravitreal dexamethasone in experimental Staphylococcus epidermidis endophthalmitis

This study was designed to investigate the efficacy of intravitreal levofloxacin, and intravitreal levofloxacin and dexamethasone combined in Staphylococcus epidermidis endophthalmitis. Albino rabbits (n = 25), infected with an intravitreal inoculum of S. epidermidis (1.0 x 10(5) colony forming units/0.1 ml), were divided into five groups (n = 5). Groups 1 and 2 received treatment 24 h after the inoculation, and groups 3 and 4 48 h after the inoculation. No treatment was given to the control group. Treatment efficacy was assessed by vitreous culture, clinical examination and histopathology. Five days after treatment, groups 1 and 2 had significantly lower clinical scores than the control group (p = 0.004, p = 0.007). The culture results of the treatment groups were sterile. The histopathological scores of the treatment groups were lower than the control group (p = 0.007). Studies on retinal toxicity and dose-response relation are needed to prove the efficacy of levofloxacin in S. epidermidis endophthalmitis.     

Effect of anterior chamber air bubble on prevention of experimental Staphylococcus epidermidis endophthalmitis

Background  

Bacterial endophthalmitis is a serious complication of penetrating ocular trauma and cataract surgery. The purpose of this study is to assess the ability of an anterior chamber air bubble to prevent experimental Staphylococcus epidermidis endophthalmitis.     

Staphylococcus epidermidis endophthalmitis following intraocular lens implantation.

A 90-year-old man developed a hypopyon following cataract extraction with intraocular lens implantation. The hypopyon cleared with topical corticosteroid therapy but recurred whenever the corticosteroid therapy was reduced. At surgery for the removal of the intraocular lens an opaque anterior vitreous membrane was excised. Cultures of the anterior vitreous grew Staphylococcus epidermidis. The diagnosis was further confirmed by the histology of the anterior vitreous membrane, which showed Gram-positive cocci in the macrophages and polymorphonuclear leucocytes. This case shows that corticosteroids may completely mask an endophthalmitis from an organism of low virulence such as Staphylococcus epidermidis. Endophthalmitis from an organism of low virulence should be considered in any case of persistent postoperative inflammation.     

Role of vitrectomy in Staphylococcus epidermidis endophthalmitis.

Seventeen patients with endophthalmitis due to coagulase-negative staphylococcus were treated over a nine-year period with vitrectomy, intraocular antibiotics, and systemic steroids and antibiotics. Fifteen patients presented with moderate to severe disease and visual acuities from counting fingers to light perception, while two had acuities of 20/60 and 20/200. A final visual outcome of 20/70 or better was achieved in 13 of 17 eyes (76%). Only one eye lost perception of light secondary to retinal detachment. Therapy including vitrectomy is an effective means of controlling moderate to severe coagulase-negative staphylococcal endophthalmitis and restoring vision.     

Staphylococcus epidermidis endophthalmitis. Visual outcome following noninvasive therapy

Staphylococcus epidermidis has been reported with increasing frequency as a cause of bacterial endophthalmitis. Over the past eight years 18 consecutive postsurgical cases have been treated by combined antibiotic-corticosteroid therapy without intravitreal antibiotics or vitrectomy. Fourteen (78%) achieved a final visual acuity of 20/50 or better. When these cases were added to similarly reported cases in the literature, 72% achieved this level of vision. By contrast, 42% of adequately documented cases in the literature treated by intravitreal antibiotics, and 42% treated additionally by vitrectomy, achieved a vision of 20/50 or better. S. epidermidis is an organism with a low order of virulence. The use of intravitreal antibiotics and vitrectomy do not appear to be necessary for effective treatment.     

玻璃体注射万古霉素治疗外源性眼内炎的研究

目的 比较去甲万古霉素和妥布霉素治疗眼内炎的疗效，探讨地塞米松联合应用的影响。方法 新西兰白兔24只随机分为A（感染对照）、B（妥布霉素）、C（去甲万古霉素）、D（去甲万古霉素联合地塞米松）组，治疗后不同时间做临床观察，14天时摘除术眼行组织病理学和电镜检查。结果 C组与B、A组炎症反应少（P＜0．05），D组比C组炎症反应少，组织结构完整（P＜0．05）。结论 玻璃体注射去甲万古霉素疗效优于妥布霉素，联合地塞米松可减轻炎症反应并防止组织破坏。     

The efficacy of intravitreal piperacillin/tazobactam in rabbits with experimental Staphylococcus epidermidis endophthalmitis: a comparison with vancomycin

BACKGROUND: To investigate the efficacy of intravitreal piperacillin/tazobactam in rabbit eyes with experimental S. epidermidis endophthalmitis and to compare the outcomes with intravitreal vancomycin application. MATERIAL AND METHODS: Twenty-four New Zealand white albino rabbits were divided into three equal groups (n=8 in each), and the right eyes received 0.1-ml intravitreal injections of S. epidermidis suspension. The left eyes served as uninfected controls and were injected with 0.1 ml of saline solution. The right eyes of rabbits in group 1 were treated with intravitreal injection of 250 microg/0.1 ml piperacillin/tazobactam 24 h after intravitreal inoculation of S. epidermidis whereas group 2 eyes received intravitreal 1 mg/0.1 ml vancomycin. Group 3 eyes received no treatment and served as infected controls. Clinical examination of the eyes in each group was performed on the 1st, 3rd and 6th day after the inoculation of S. epidermidis. On the 6th day, 0.1-ml vitreous aspirates were obtained for microbiological analysis, and then the eyes were enucleated for histopathological evaluation. RESULTS: There were no statistically significant differences in mean clinical scores between the groups on the first day after S. epidermidis inoculation (p>0.05). On the 6th day, the mean clinical score of group 3 was significantly higher (p<0.001), but the mean clinical scores of groups 1 and 2 were similar (p=0.812). The mean logarithmic value of colony-forming units per milliliter of groups 1, 2 and 3 were 0.6+/-1.3, 0.5+/-1.5 and 5.3+/-0.7, respectively. Mean histopathological scores of the groups were 8.3+/-0.9, 7.5+/-1.3 and 15.6+/-1.2, respectively. Group 3 eyes had significantly more colony-forming units per milliliter and a higher histopathological score (for each, p<0.001), and there were no statistically significant differences in microbiological and histopathological scores between groups 1 and 2 (for each, p>0.05). CONCLUSION: Intravitreal application of 250 microg/0.1 ml piperacillin/tazobactam seems to be approximately equally effective with intravitreal 1 mg/0.1 vancomycin application in the treatment of experimental S. epidermidis endophthalmitis. Therefore, intravitreal piperacillin/tazobactam may be an alternative therapeutic option in the treatment of S. epidermidis endophthalmitis.     

Infectious crystalline keratopathy and endophthalmitis caused by a slime producing Staphylococcus epidermidis strain

A case of infectious crystalline keratopathy with secondary endophthalmitis, caused by a slime producing Staphylococcus epidermidis in a patient with pseudophakic bullous keratopathy. Histopathology of the corneal button, after penetrating keratoplasty failed to exhibit cells of the causative organism. S. epidermidis, though generally of low pathogenicity, may become an important pathogen affecting the intraocular tissues in compromised corneas. The authors have stated that they do not have a significant financial interest or other relationship with any product manufacture or provider of services discussed in this article. The authors also do not discuss the use of off-label products, which includes unlabeled, unapproved, or investigative products or devices.