Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

紫萁贯众单体成分对小鼠SIRS模型的保护作用

目的:建立小鼠全身炎症反应综合征(SIRS)模型,探索紫萁贯众醇提取物中单体成分对羟基苄叉丙酮(4-hydroxybenzylideneacetone,HBAc),3,4-二羟基苄叉丙酮(3,4-dihydroxybenzylideneacetone,DHBAc)对SIRS模型小鼠的保护作用及机制。方法:BALB/c小鼠随机分为正常组,模型组,HBAc,DHBAc低、中、高剂量(25,50,100μg·kg~(-1))组。预防给药7 d后腹腔注射脂多糖(LPS),造模5 h后检测小鼠肛温、呼吸频率、白细胞、血小板计数、白细胞分类、糖脂代谢以及肺组织炎症因子和炎症相关蛋白磷酸化情况。结果:与正常组比较,模型组小鼠腹腔注射LPS(6 mg·kg~(-1))可致小鼠呼吸频率降低(P0.05),体温明显降低(P0.01),外周血白细胞数和单核细胞百分比增加(P0.01),血小板减少(P0.01),血糖水平降低(P0.05),肺组织中白细胞介素-1β分泌增多(P0.01)。与模型组比较,HBAc,DHBAc均明显增加动物呼吸频率,升高动物体温,降低外周白细胞水平以及单核细胞百分比(P0.05,P0.01),并显著升高血糖水平(P0.05,P0.01),减少肺组织中白细胞介素-1β的分泌(P0.01)。结论:腹腔注射LPS致小鼠SIRS模型成立,HBAc,DHBAc对LPS致小鼠SIRS模型有一定的保护作用,可能通过IκB,c-JUN通路发挥抗炎作用。     

清热解毒、散风除翳法对细菌性角膜炎的作用机制研究

目的:观察清热解毒、散风除翳法对细菌性角膜炎模型鼠的疗效及其作用机制。方法:将60只Wistar大鼠随机分为5组,即模型组、小剂量组、大剂量组、对照组以及空白组，每组12只大鼠。采用细菌性角膜炎动物模型症状评定观察清热解毒、散风除翳法的疗效,通过细菌清除率、角膜细菌菌落计数,光学显微镜观察大鼠角膜的病理组织学改变,并采用流式细胞仪检测CD4+,CD8+及CD4+/CD8+的水平讨论清热解毒、散风除翳法的作用机制。结果:1)清热解毒、散风除翳法可降低细菌性角膜炎性反应状评分,提高细菌清除率,改善角膜基质层的病理结构;2)清热解毒、散风除翳法可提高细菌性角膜炎模型鼠外周血血CD4+、CD8+的表达水平,具有剂量依赖性(P<0.05),CD4+/CD8+比值相对稳定,各组间差异无统计学意义(P>0.05)。结论:清热解毒,散风除翳法能有效改善细菌性角膜炎,其作用机制可能与上调大鼠外周血中CD4+,CD8+含量有关。     

肠道细菌性疫苗研究进展

人肠道致病菌具有高度传染性，可引起多种疾病。目前已有多种肠道细菌灭活疫苗和减毒活疫苗通过安全性评价上市；重组蛋白疫苗、结合疫苗和亚单位疫苗等新型疫苗的研究已获得较好的结果。此文对人肠道致病菌及其相关新疫苗的研究进展做一综述。     

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates.ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands.MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017.ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands.ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.     

Er:YAG激光联合牙周基础治疗对牙周炎患者病灶区相关指标及红白美学的影响

目的:分析Er:YAG激光联合牙周基础治疗对牙周炎患者牙周指标、龈沟液内炎性因子和内毒素(LPS)含量及红白美学效果的影响。方法:选取2015年12月-2018年12月在北部战区总医院和沈阳市口腔医院接受治疗的慢性牙周炎患者80例,随机分成对照组和观察组。对照组:40例,行牙周基础治疗;观察组:40例,在对照组基础上行Er:YAG激光治疗;观察两组患者临床疗效、出血指数(BI)、探针深度(PD)、菌斑指数(PLI)、临床附着丧失(CAL)及龈沟内液白细胞介素-21(IL-21)、IL-17、肿瘤坏死因子-α(TNF-α)、内毒素(LPS)含量及红白美学效果。结果:观察组和对照组患者总有效率分别为92.50%、77.50%,差异有统计学意义(P<0.05);治疗后8周,观察组患者PLI、PD、BI及CAL较治疗前、对照组降低,差异有统计学意义(P<0.05);治疗后8周,观察组患者龈沟液内TNF-α、IL-17、IL-21及LPS含量较治疗前、对照组降低,差异有统计学意义(P<0.05);治疗后8周,观察组患者WES、PES及PES/WES评分均高于对照组,差异有统计学意义(P<0.05)。结论:Er:YAG激光联合牙周基础治疗可显著缓解患者临床症状,降低牙周炎症反应程度,提升患牙红白美学效果,改善其生活质量。     

Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis

PurposeReport the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis.MethodsA retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention.ResultsThe cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73%, 64%, and 44% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure.ConclusionCTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.     

细菌与病毒感染的鉴别

急性感染早期准确鉴别细菌和病毒感染一直是临床面临的挑战,随着临床各种检验、检测技术的快速发展、长足进步,越来越多的病原学、人体基因学、分子生物学指标用于鉴别细菌与病毒感染。未来将有更多的检测指标采用床旁即时检测方式便于临床应用;将有更精准、丰富的生物医学信息平台和更高效的医院信息系统,进行多指标综合分析,提供更精准的病原诊断,有助于最佳临床实践的实施。     

Queratitis bacteriana por Moraxella nonliquefaciens

Moraxella keratitis can lead to important complications. Moraxella nonliquefaciens (M. nonliquefaciens) has the worst prognosis. Only three cases of corneal infections due to M. nonliquefaciens have been published. The case is presented of a 79-year-old man with bullous keratopathy, recently affected with severe infectious keratitis. Dense, deep, and central stromal infiltrates and hyphaema were detected. After the identification of M. nonliquefaciens in the culture, and given the progression of the condition, the initial empirical treatment was modified to topical ciprofloxacin and ceftazidime in accordance with the antibiogram, combining oral ciprofloxacin and amoxicillin-clavulanate. After 27 days, there was total resolution of the lesion, with central residual leucoma.Keratitis caused by M. nonliquefaciens is rare and must be suspected in elderly patients with local predisposing factors, such as corneal damage or previous eye surgery. Early antibiogram-guided treatment and close monitoring are important to avoid complications and poor compliance.