金黄色葡萄球菌眼内炎模型的建立及实验室诊断

目的 建立外源性金黄色葡萄球菌性眼内炎动物模型。方法 新西兰种大耳白兔24只，分为空白对照组及3个实验组，后者分别于眼内注入不同浓度的金黄色葡萄球菌。又分为高浓度组(10^4CFU／mL)，中浓度组(10^3CFU／mL)和低浓度组(10^2CFU／mL)。结果 (1)3组术后均有不同程度炎症反应，术后24小时～3天角膜浑浊，前房渗出或积脓；3．7天炎症反应开始减轻；10～14天玻璃体呈灰白色浑浊。(2)细菌培养于术后12～24小时阳性率最高，3组分别为100％、100％、33％；术后3天阳性率明显下降，7～10天阳性率为0％。(3)病理学变化：术后1～12小时虹膜和睫状体充血，眼内炎性细胞浸润；术后24小时视网膜下渗出和视网膜脱离；术后3～7天为全眼球炎。结论 成功建立金黄色葡萄球菌眼内炎动物模型；确立了实验室诊断方法。     

玻璃体内注射包载盐酸去甲万古霉素的聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒治疗兔眼混合细菌性眼内炎的效果

目的 探讨玻璃体腔内注射包栽盐酸去甲万古霉素(norvancomycin,NV)的聚N-异丙基丙烯酰胺-聚氧化乙烯[poly(N-isopropyl acrylamide)-polyethylene oxide,PNIPAAm-PEO]纳米缓释给药系统(NV-PNIPAAm-PEO)治疗兔混合细菌性眼内炎模型的效果.方法 选取健康成年新西兰兔50只,每只随机选取1眼向玻璃体腔内注入100×103CFU·L-1的金黄色葡萄球菌和大肠埃希杆菌混合悬液建立眼内炎模型.建模成功后24 h,将实验动物随机分为1个空白对照组(A组)和4个实验组(B组、C组、D组和E组),每组10眼.A组不作任何处理;B组、C组、D组和E组分别向玻璃体腔内注入0.1 mL的空白纳米粒(20 g·L-1)、无菌生理盐水、盐酸去甲万古霉素原药(4.4 g·L-1)和NV-PNIPAAm-PEO(20 g·L-1).于给药后第1、2、3、7、14、21、28、42天分别进行临床炎症评分、眼部A/B超检查及组织病理学检查.结果 A组、B组和C组各时间点眼内炎病变程度无明显差异;D组和E组炎性反应较A组、B组和C组轻(P<0.005);E组与D组在术后21 d内无差异,21 d后E组玻璃体腔混浊程度较D组明显减轻(P<0.005).眼部A/B超检查,术后7 d之后A组、B组和C组可见玻璃体内团块状回声伴点状或短线状回声点;D组在42 d后仍可见玻璃体腔轻度混浊;E组注药后7-14 d可见玻璃体内点线状回声,回声强度较同时期A组、B组和C组弱,21 d后未见明显异常回声.组织病理学检查见A组、B组和C组眼球结构被破坏,D组近后极部视盘前方玻璃体腔内少量淋巴细胞及浆细胞浸润,E组眼球结构正常,未见典型炎性细胞.结论 NV-PNIPAAm-PEO纳米粒玻璃体腔注射治疗细茵性眼内炎疗效确切,与单纯盐酸去甲万古霉素眼内注射相比,具有缓释及药效持久等特性.     

曲安奈德兔眼内注射治疗金黄色葡萄球菌眼内炎的有效性

目的:正确评价曲安奈德作为金黄色葡萄球菌性眼内炎辅助治疗的有效性。方法:30只健康青紫蓝兔所有右眼玻璃体腔注射ATCC25923标准金黄色葡萄菌104CFU/0.1mL混悬液,0.1mL建立眼内炎模型。建立眼内炎模型后24h,随机将实验动物分为3组,每组10眼进行不同干预,A(空白对照)组、B(玻璃体腔万古霉素)组、C(玻璃体腔万古霉素 曲安奈德混悬剂)组。干预后每日间接眼底镜观察结膜、角膜、前房、虹膜、玻璃体的变化并按照规定的时间进行临床炎症评分;注射细菌后24h及干预后14d所有实验动物行B超检查;干预后5d进行玻璃体腔细菌学培养;干预14d后处死所有动物行光镜检查并进行病理评分。结果:B,C组较A组炎症明显减轻。不同时间3组进行临床炎症评分,A组评分明显高于B,C2组,A,B,C3组间评分均有显著性差异(P<0.05),5,7,14d验证评分B,C2组间均无显著性差异(P=0.717,0.694,0.543);7,14d前房闪辉分级B,C组间无显著性差异(P=0.796,0.562);A,B,C3组间细菌学培养检出率无统计学意义;B超显示A,B,C3组视网膜脱离发生率无显著性差异(P=0.830);光镜下见A组各组织结构均失去正常形态不易辨认;B、C组组织结构能够辨认。对角膜、前房、玻璃体、视网膜进行病理评分,A,B,C3组间有显著性差异(P=0.000),组间比较B,C视网膜分级有显著性差异(P=0.011),其余均无显著性差异。结论:金黄色葡萄球菌性眼内炎治疗中玻璃体腔注射曲安奈德对眼组织的保护作用具有局限性。     

16S rDNA测序技术对细菌性眼内炎房水和玻璃体标本中细菌的鉴别作用

背景 眼内炎是多种内眼手术的严重并发症,以往感染菌的确定多采用细菌培养和涂片染色法,但存在花费时间长和阳性率低的问题.16S rDNA是细菌染色体上编码rRNA的序列,利用16S rDNA分子测序技术检测细菌具有高度的特异性. 目的 利用16S rDNA测序技术对细菌性眼内炎房水和/或玻璃体标本中的感染菌进行鉴定,探讨该技术在眼部感染性炎症诊断中的作用.方法 收集2015年6-12月在青岛眼科医院临床诊断为细菌性眼内炎的患者5例5眼,抽取每例患者的房水0.1～0.2 ml或玻璃标体标本0.5 ～1.0ml,各取50 μl用于高通量测序,剩余标本行涂片检查和细菌培养.采用D3096-01微量DNA试剂盒提取标本中细菌DNA,对收集的标本DNA样品进行16S rRNA基因V3-V4区PCR扩增,应用MiSeq 300测序仪对扩增的16S rDNA高变区序列进行测序,分析标本中病原菌的分类组成、分布特点以及各病原菌在标本中的相对含量,取50 μl无RNA酶水于一次性无菌离心管内作为空白对照. 结果 共收集到5份房水或玻璃体标本,涂片染色结果阳性者2例,外伤性细菌性眼内炎为革兰阳性杆菌,滤过泡感染性细菌性眼内炎为革兰阴性杆菌,而细菌培养法结果均为阴性.16S rDNA测序技术发现,5例标本检测阳性率为100％.外伤性细菌性眼内炎标本中高丰度菌属为葡萄球菌属、链球菌属和假单胞菌属,分别占65.28％、18.90％和12.76％;白内障术后2d急性细菌性眼内炎患眼标本中高丰度菌属有假单胞菌属、不动杆菌属和Limnobacter菌属,分别占53.68％、8.62％和5.96％;滤过泡感染性细菌性眼内炎标本中高丰度菌属有莫拉菌属和假单胞菌属,分别占88.89％和9.52％;白内障术后22 d迟发性细菌性眼内炎标本中相对含量较高的菌属有假单胞菌属,占84.63％;白内障术后1d急性细菌性眼内炎患眼标本中相对含量较高的有假单胞菌属,占97.89％.结论 16S rDNA测序可准确鉴别眼内炎患者房水和玻璃体标本中的致病菌,该方法检测的阳性率明显高于传统的涂片染色法和细菌培养法.     

妥布霉素滴眼液对家兔细菌性角膜炎体内外抗菌作用

目的:研究妥布霉素滴眼液的抗菌作用.方法:体外采用M-H肉汤稀释法,妥布霉素滴眼液对大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌、肺炎克雷伯菌、肺炎链球菌进行体外抑菌、杀菌试验.体内用角膜环钻损伤兔眼角膜,感染大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌造成角膜炎动物模型.然后用妥布霉素滴眼液滴眼4次/d,每眼0.1mL,连续给药7d.d8处死家兔.以观察角膜病理切片,临床症状评分统计学t检验处理及角膜分泌物细菌培养判断疗效.结果:体外试验表明妥布霉素滴眼液对上述6种细菌最低杀菌浓度(MBC)分别为0.19,0.39,0.78,46.88,93.75,187.50μg/mL.体内抗菌试验显示,家兔眼感染大肠埃希菌、金黄色葡萄球菌、绿脓杆菌、化脓性链球菌感染后,妥布霉素滴眼液在治疗3d评分结果与未治疗对照组比较均有显著差异,5d细菌培养转阴率大肠埃希菌、金黄色葡萄球菌、绿脓杆菌均为100%,化脓性链球菌83%.角膜病理结果显示除化脓性链球菌伤口愈合较慢,余3种菌伤口斑痕愈合良好.结论:妥布霉素滴眼液对大肠埃希菌、金黄色葡萄球菌、绿脓杆菌敏感性较强;所致家兔角膜炎治疗效果较好,化脓性链球菌、肺炎克雷伯菌、肺炎链球菌对其敏感性较弱.     

大肠杆菌内毒素诱导的大鼠眼内炎表现及细胞因子的表达

目的 观察大肠杆菌内毒素(LPS)诱导的大鼠眼内炎模型组织病理学特征和玻璃体内肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和LPS的表达模式.方法 采用随机数字表法将大鼠随机分为生理盐水对照组(SC组)136只、眼内炎组(EO组)168只、空白对照组(BC组)12只.E0组玻璃体腔注射5 μl LPS溶液诱导眼内炎动物模型;SC组注入等量无菌生理盐水;BC组不作任何干预.注射后6、12、24、48、72 h,5、7 d,观察大鼠眼部炎症表现并分别摘除各组眼球行组织病理学检查,并取其玻璃体检测细胞因子TNF-α、IL-1β和LPS的浓度.结果 EO组注射后6～72 h,眼内可见严重炎症反应,注射后7 d炎症基本消退.注射后24 h,眼内白细胞浸润数量为(1224.64±132.2)个/眼,达到高峰;注射后72 h,浸润细胞数量迅速下降至(342.25±47.7)个/眼.EO组注射后24 h,TNF-α和IL-1β浓度分别为(996.18±89.45)、(5556±1440)pg/ml,均达到高峰并持续至注射后48 h,随后迅速下降;注射后7 d,TNF-α和IL-1β浓度分别为(22.16±5.84)、(73.7±18.7)pg/ml.EO组注射后72 h,玻璃体腔内LPS含量迅速下降为(11.03±3.41)ng,7 d后玻璃体腔内LPS含量为(0.22±0.08)ng.结论 大鼠眼内炎模型的主要病理特征是大量白细胞眼内浸润,TNF-α、IL-1β的高水平表达以及玻璃体腔自发性细菌成分清除;TNF-α、IL-1β表达模式与LPS眼内清除过程一致.     

玻璃体切割术联合组织型纤溶酶原激活物和速避凝治疗兔细菌性眼内炎所致纤维蛋白渗出

目的 探讨玻璃体切割联合组织型纤溶酶原激活物（r-tPA）和速避凝治疗细菌性眼内炎的效果。 方法 将40只青紫兰家兔随机分为实验组和对照组，每组各20只。向兔左眼玻璃体腔内注射105个/ml表皮葡萄球菌0.1 ml，经过8～14 h后，所有动物均接受玻璃体切割手术。手术中在实验组使用的平衡盐灌注液内加入速避凝，其终浓度为6 IU/ml；手术后运用裂隙灯和间接检眼镜观察眼内纤维蛋白渗出的程度。若实验组手术后1、3、7、14、21 d眼内存在纤维渗出，从手术后第1天开始向玻璃体腔内注射125 mg/ml的r-tPA 0.1 ml。 结果 手术后实验组兔眼瞳孔区及玻璃体腔内纤维渗出较对照组显著减轻。 结论 玻璃体切割术联合r-tPA和速避凝的应用，能减轻兔细菌性眼内炎的纤维化程度，改善预后。 (中华眼底病杂志, 2005, 21: 391-393)     

眼内炎的病因及其预防

严格地说,眼内炎是指眼球壁的一层或层膜及相邻眼内腔的炎症。但在临床上,本术语常指视网膜、脉络膜和玻璃体腔的潜在性破坏性炎症。本文从病因和预防这两个方面,对外源感染性、内源感染性和非感染性等各类眼内炎进行论述。一、眼内炎的病因 (一)外源感染性眼内炎的病因外源性感染多由需氧菌引起,偶尔也可由厌氧菌或真菌导致。 1.术后眼内炎术后培养呈阳性的眼内炎病例,革兰氏阳性需氧菌约占90％,革兰氏阴性细菌约占7％,真菌39％。20～50％的病例,致病菌是表皮葡萄球菌。其它可致术后眼内炎的革兰氏阳性需氧菌,有金黄色葡萄球菌、肺炎链球菌、绿色链球菌、酿脓链球菌和棒状杆菌属。另外,还曾分离出革兰氏阳性厌氧菌-胨链球菌、疮疱丙酸杆菌和梭状芽孢杆菌属。虽然还有别的致病菌,如变形杆菌,流感嗜血杆菌,肺炎克雷伯氏杆菌,埃希氏大肠杆菌和产气肠杆菌等,但引起细菌性眼内炎最常     

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。     

万古霉素在正常兔眼和细菌性眼内炎兔眼内的药代动力学研究

背景万古霉素近年来常被作为金黄色葡萄球菌性眼内炎治疗的首选药物,万古霉素在眼内药代动力学的研究报道较少。目的观察万古霉素在正常兔眼和细菌性眼内炎兔眼房水、玻璃体及血清中质量浓度的变化,并进行药代动力学参数比较。方法选取健康成年兔72只,采用随机数字表法分为正常组和眼内炎组,每组36只。眼内炎组兔右眼玻璃体腔内接种2000CFU／ml金黄色葡萄球菌建立眼内炎模型,注射后72h待出现典型的眼内炎表现时,兔眼玻璃体腔内注射10g／L万古霉素注射液0．1ml,分别于注射后0．5、2、4、6、12、24、48、72、84h经兔耳缘静脉采血2ml,之后以空气栓塞法处死动物,摘除眼球,收集房水和玻璃体,利用高效液相色谱仪紫外（HPLC—UV）法检测万古霉素在血液、房水和玻璃体内的质量浓度。3p97药代动力学软件拟合药代动力学参数。结果HPLC法的准确度和精确度符合生物样品的检测要求。玻璃体腔内注射万古霉素后,其在正常兔眼内的代谢呈二室模型,拟合曲线的高峰质量浓度Cmax分别为50．16mg／L和751．42mg／L,t1/2为51．04h和53．21h;其在金黄色葡萄球菌性眼内炎兔眼中代谢呈一室模型,高峰质量浓度Cmax分别为24．94mg／L和687．66mg／L,t1/2分别为11．42h和12．91h,2组动物血药质量浓度均较低,差异无统计学意义（P〉0．05）。正常组和眼内炎组玻璃体腔内注射万古霉素后随时间延长,玻璃体中万古霉素的质量浓度逐渐下降,而房水中出现先升高后下降的趋势。与正常组相应时间点比较,眼内炎组玻璃体和房水中万古霉素的质量浓度均明显下降,差异均有统计学意义（P〈0．05,P〈0．01）。结论HPLC能满足万古霉素药代动力学分析的需要;万古霉素在正常兔眼内的质量浓度较高,清除缓慢,而在细菌性眼内炎兔眼中质量浓度较低、清除较快。     

Effects of intravitreal corticosteroid in the treatment of Staphylococcus aureus-induced experimental endophthalmitis

PURPOSE: To investigate whether intravitreal injection of dexamethasone in addition to antibiotics can minimize intraocular tissue injury caused by Staphylococcus aureus endophthalmitis. METHODS: Albino rabbits were infected with an intravitreal injection of 1000 colony-forming units of S. aureus. The rabbits were randomized to receive no treatment (control group; n = 2), intravitreal vancomycin and amikacin (n = 5), or a combination of intravitreal vancomycin, amikacin, and dexamethasone (n = 5) 20 hours following inoculation of bacteria. All rabbits except for the control group also received intravenous imipenem every 8 hours for 4 days. The eyes were evaluated by clinical examination, electroretinogram (ERG), and histologic studies. RESULTS: Eyes treated with intravitreal dexamethasone demonstrated less inflammation on clinical examination compared with eyes that received antibiotics alone. The ERG responses of eyes that received both intravitreal antibiotics and steroid were significantly better at 45 hours, 7 and 14 days following inoculation (P < 0.05) compared to eyes that received antibiotics alone. Histologic studies 14 days following infection demonstrated less tissue destruction for eyes treated with dexamethasone. CONCLUSION: Compared to intravitreal antibiotics alone, intravitreal corticosteroids may improve visual outcome of S. aureus endophthalmitis by reducing inflammation and preserving electrophysiologic retinal function.     

Experimental prophylaxis of Staphylococcus aureus endophthalmitis after vitrectomy: the use of antibiotics in irrigating solution.

PURPOSE: To test the efficacy of clindamycin and gentamicin in irrigating solution during vitrectomy to prevent experimental Staphylococcus aureus endophthalmitis. MATERIALS AND METHODS: Thirty-six New Zealand white rabbits were divided into six groups. Vitrectomy using two different irrigating solutions was followed by intravitreal injection of S. aureus: Group 1, balanced salt solution (BSS) followed by 1,000 colony-forming units (CFU) S. aureus; Group 2, BSS fortified with clindamycin, 10 microg/mL, and gentamicin, 8 microg/mL (CGBSS), followed by intravitreal injection of 1,000 CFU S. aureus; Group 3, BSS followed by 2,000 CFU S. aureus; Group 4, CGBSS followed by 2,000 CFU S. aureus; Group 5, BSS followed by 4,000 CFU S. aureus; and Group 6, CGBSS followed by 4,000 CFU S. aureus. The eyes were examined clinically after surgery. Vitreous samples were cultured and histologic studies were performed. RESULTS: Severe endophthalmitis developed in all eyes in Groups 1, 3, and 5 (not given antibiotics). No endophthalmitis developed in Group 2. In Group 4, five of the six eyes were normal and one eye had endophthalmitis. In Group 6, one eye had clear vitreous and fundus, three eyes had moderate vitreous haze, and the other four eyes demonstrated severe endophthalmitis. Bacterial growth in Groups 1, 2, 3, 4, 5, and 6 were 4/4, 0/4, 6/6, 1/6, 4/6, and 2/8 eyes, respectively. CONCLUSION: When 1,000 to 2,000 CFU S. aureus were injected after vitrectomy, clindamycin and gentamicin in the irrigating solution significantly diminished the intraocular inflammation and the rate of positive bacterial culture. Clindamycin and gentamicin in the irrigating solution were not significantly effective when 4,000 CFU bacteria was injected; however, the degree of inflammation was less severe than in the control group.     

High dose intramuscular methylprednisolone in experimental Staphylococcus aureus endophthalmitis.

We attempted to determine whether treatment using intramuscular methylprednisolone plus intravitreal vancomycin decreased ocular inflammation and preserved retinal function better in experimental Staphylococcus aureus (S. aureus) endophthalmitis than treatment with intravitreal vancomycin alone. Sixteen rabbits received intravitreal inoculations in both eyes with S. aureus and the rabbits were divided into two groups (group I and group II) of eight rabbits each. Group I rabbits were treated with one injection of intravitreal vancomycin in each eye at either 24, 36, 48 or 72 hours after bacterial inoculation followed by seven consecutive days of high dose intramuscular methylprednisolone (30 mg/kg per day). Group II rabbits were treated with only one intravitreal injection of vancomycin in each eye at equivalent time intervals as in Group I. Clinical evaluations of ocular inflammation were performed by slit-lamp biomicroscopy and indirect ophthalmoscopy. Electroretinography (ERG) was performed eight days after bacterial inoculation to assess retinal function in all eyes. The combination of intramuscular methylprednisolone and intravitreal vancomycin resulted in a degree of ocular inflammation equal to eyes treated with intravitreal vancomycin alone at all treatment intervals. ERG responses were not significantly different in either group. A single intravitreal injection of vancomycin plus daily intramuscular methylprednisolone for seven days were found neither to decrease ocular inflammation nor preserve retinal function better than a single intravitreal injection of vancomycin in our experimental model of S. aureus endophthalmitis.     

Effects of intravitreal moxifloxacin and dexamethasone in experimental Staphylococcus aureus endophthalmitis

PURPOSE: To evaluate the effects of intravitreal moxifloxacin and moxifloxacin and dexamethasone combination in an experimental rabbit model of Staphylococcus aureus endophthalmitis. METHODS: The right eyes of 24 rabbits weighing 2 to 3 kg were used. Ten thousand colony-forming units (CFU) of S. aureus in 0.1 ml saline solution were inoculated into the vitreous cavity. The eyes were randomly assigned to one of the four groups equally. Twenty-four hours after the inoculation of S. aureus, group 1 received 50 microg moxifloxacin, group 2 received 50 microg moxifloxacin plus 400 microg dexamethasone, and group 3 received 1 mg vancomycin intravitreally. No treatment was given to group 4. Clinical examination scores were recorded. Vitreous aspirates were obtained for microbiological analysis just before sacrifice, and the eyes were enucleated for histopathologic examination. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests. RESULTS: In all treatment groups, mean number of CFU and histopathologic score were significantly lower compared with control group (p<0.05), and the difference between treatment groups was not statistically significant (p>0.05). The clinical score was not significantly different between groups (p>0.05). CONCLUSIONS: Intravitreal injection of 50 microg moxifloxacin was effective in the treatment of S. aureus endophthalmitis. Bacteriological, histopathologic, and clinical outcomes after treatment using moxifloxacin, moxifloxacin and dexamethasone combination, and vancomycin were comparable. Intravitreal moxifloxacin may be an option in the treatment of S. aureus endophthalmitis.     

万古霉素在不同病理状态兔眼内炎模型中药代动力学研究

目的 观察不同病理状态兔眼玻璃体内万古霉素的浓度和药代动力学参数.方法 健康成年白化兔81只,随机分为有晶状体细菌性眼内炎组(A组)、晶状体摘除手术后细菌性眼内炎组(B组)及晶状体摘除手术后眼内炎并行玻璃体切割手术组(C组),每组27只.所有兔右眼玻璃体腔注射浓度为10 mg/ml的万古霉素溶液1 ml.注射后0.5、2.0、4.0、6.0、12.0、24.0、48.0、72.0、84.0 h,每组注气处死3只兔,摘取眼球,收集玻璃体样品.采用高效液相色谱法(HPLC-UV)检测各组兔眼玻璃体内万古霉素浓度.应用3p 97药代动力学软件拟合并计算3组玻璃体内万古霉素的药-时曲线下面积(AUC)、清除率(CL)、半衰期(t1/2)及峰值浓度(Cmax)等药代动力学参数.结果 玻璃体腔注射万古霉素后各时间点,A组万古霉素浓度均高于治疗浓度.玻璃体腔注射后0.5、2.0、4.0、6.0、12.0h,B、C组万古霉素均维持较高浓度;玻璃体腔注射后24、48 h,浓度下降较快;玻璃体腔注射后72 h,浓度低于最低抑菌浓度.注射后不同时间点3组万古霉素浓度比较,A组与B、C组间差异均有统计学意义(P＜0.05);B、C组间差异无统计学意义(P＞0.05).A、B、C组万古霉素AUC分别为15 790.61、7643.94、7443.44 μg/(ml·h),CL分别为0.063、0.131、0.134ml/h,t1/2分别为13.49、7.15、6.93 h,Cmax分别为711.56、648.45、667.74μg/ml.A组与B、C组比较,万古霉素AUC较大(t=4.963,5.097;P＜0.01),CL较低(t=2.963,3.097;P＜0.05),t1/2较长(t=3.315,3.481; P＜0.01);但Cmax无明显差异(t=1.687,1.214;P＞0.05).结论 不同病理状态兔眼玻璃体内万古霉素的浓度及其药代动力学参数均存在一定差异.     

Dispase诱发兔眼玻璃体后脱离的效果和安全性评价

目的 采用Dispase在兔眼中诱导完全性PVD形成，评价其效果和安全性。方法 选择健康成年的青紫蓝兔30只，随机分成5组，采用玻璃体内注射，分别注射Dispase0.005U,0.0125U(2组），0.025U,0.05U/0.05ml,PBS0.05ml注射到另一只内作为对照。术前术后眼底镜，裂隙灯和VOLK 90D随访观察。并进行B超和视网膜电图（ERG）检查，最后取眼球对视网膜进行扫描电镜和透射电镜观察。结果 注射Dispase≥0.0125U可见玻璃体后脱离，部分伴有不同程度的眼底出血：B型超声检查见玻璃体混浊和后脱离；术后电生理检查，0.005U和0.0125U组ERG没有变化，≥0.025U，部分出现ERG振幅下降；对照组没有以上改变。结论 Dispase0.0125U可以在兔眼中成功，安全诱发完全性玻璃体后脱离（PVD），更大剂量同样有效。但是有一定毒性作用。     

头孢哌酮/舒巴坦玻璃体腔注射治疗兔铜绿假单胞菌性眼内炎

目的评价头孢哌酮/舒巴坦治疗铜绿假单胞菌眼内炎的疗效。方法青紫蓝兔18只,随机分为3组,右眼注菌后6h分别注入100g/L头孢哌酮/舒巴坦、22.5g/L头孢他啶和生理盐水各0.1mL,观察24h。另取青紫蓝兔12只,随机分为2组。早期注药组注菌后6h注入100g/L头孢哌酮/舒巴坦0.1mL,晚期注药组注菌后20h注入100g/L头孢哌酮/舒巴坦0.1mL,观察1周。结果头孢哌酮/舒巴坦组、头孢他啶组与生理盐水组比较除角膜评分外（P〉0.05）,结膜、前房、玻璃体、视网膜、B型超声检查及组织病理学评分结果差异均有统计学意义（P〈0.05）;头孢哌酮/舒巴坦组与头孢他啶组相比,除虹膜炎症反应评分差异有统计学意义外（P〈0.05）,其他评分差异均无统计学意义（P〉0.05）,但从具体评分来看头孢哌酮/舒巴坦组优于头孢他啶组。早期注药组与晚期注药组相比,1周后结膜、前房、虹膜、玻璃体、视网膜、B型超声检查及组织病理学评分差异均有统计学意义（P〈0.05）。结论 100g/L头孢哌酮/舒巴坦0.1mL玻璃体腔注射治疗早期铜绿假单胞菌眼内炎有效。     

Evaluation of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> staphylolysin (LasA protease) in the treatment of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> endophthalmitis in a rat model

Background  Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity. Methods  Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50–160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection. Results  In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055 ± 3,144 and 6,432 ± 6,389 CFU/vitreous, respectively; P = 0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148 ± 3,096 and 143,519 ± 151,358 CFU/vitreous, respectively; P = 0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin. Conclusions  Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans. The authors have no proprietary interest in any aspect of this study. The authors have full control of all primary data, and they agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

Rapid detection of experimental E. coli endophthalmitis by the Limulus lysate test.

Experimental E. coli endophthalmitis was produced in rabbits. The Limulus lysate test was applied to aqueous and vitreous samples at various intervals after the intravitreal injection of E. coli organisms. Results indicated that this test is feasible using vitreous and aqueous samples. The Limulus test was positive for E. coli endotoxin within hours after infection, requiring only 1 hr to determine the presence of endotoxin after sampling. This test may have some value in the rapid diagnosis of gram-negative endophthalmitis.