Staphylococcus aureus,master manipulator of the human hemostatic system

Summary

The coagulation system does not only offer protection against bleeding, but also aids in our defense against invading microorganisms. The hemostatic system and innate immunity are strongly entangled, which explains why so many infections are complicated by either bleeding or thrombosis. Staphylococcus aureus (S. aureus), currently the most deadly infectious agent in the developed world, causes devastating intravascular infections such as sepsis and infective endocarditis. During these infections S. aureus comes in close contact with the host hemostatic system and proves to be a master in manipulating coagulation. The coagulases of S. aureus directly induce coagulation by activating prothrombin. S. aureus also manipulates fibrinolysis by triggering plasminogen activation via staphylokinase. Furthermore, S. aureus binds and activates platelets and interacts with key coagulation proteins such as fibrin(ogen), fibronectin and von Willebrand factor. By manipulating the coagulation system S. aureus gains a significant advantage over the host defense mechanisms. Studying the interplay between S. aureus and the hemostatic system can therefore lead to new innovative therapies for battling S. aureus infections.

     

Stability of Cefazolin in Polyisoprene Elastomeric Infusion Devices

Purpose

The aim was to investigate the stability of cefazolin in elastomeric infusion devices.

Anatomical definition of aortic root abscesses by transesophageal echocardiography: Planning a surgical strategy using homograft valves

Infective endocarditis of the native or a prosthetic aortic valve may be complicated by abscess cavity development in the aortic root, and successful treatment depends upon early diagnosis, clear anatomical definition preoperatively, and maintaining sterility of the second implant. Homograft valves offer many advantages in this setting. Timing of surgery and the choice of the particular technique depends on accurate characterization of the anatomical details of the abscess. Five cases of paravalvular aortic root abscess in the setting of prosthetic valve endocarditis are described. In each case the diagnosis was made with transesophageal echocardiography, and the information was used in planning the operative procedure of homograft valve replacement. This strategy is proposed as optimal management of this potentially lethal condition.     

Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis.

Infective endocarditis is associated with significant morbidity and mortality, with valvular destruction and congestive heart failure being more common in patients with echocardiographically discernible vegetations. The transoesophageal approach affords consistently high quality images with excellent structural resolution. Two-hundred and eighty-one patients with clinically suspected infective endocarditis were studied, to evaluate the prognostic value of ascertaining the site of vegetations. Among them were 118 patients with vegetations attached to the aortic or mitral valve. These patients were followed for a mean period of 14 months. Mitral valve vegetations were associated with a significantly higher incidence of embolic events than vegetations on aortic valves (25% vs 9.7%). The incidence of abscess formation was higher in aortic than in mitral valve endocarditis (6% vs 0%), as were the need for surgical intervention (11% vs 5.5%) and mortality (1.6% vs 0%) respectively). Bivalvular endocarditis was associated with an increased rate of complications: embolism (50%), abscess formation (15%), surgery (35%) and mortality (10%). By multivariate analysis, echocardiographically accessible risk factors for subsequent embolism were a vegetation size of more than 10 mm and mitral valve involvement. Risk factors associated with in-hospital fatality were embolism, a vegetation size of more than 10 mm, and Staphylococcus aureus infection. Our data suggest that the site influences both the rate and the type of complications. Precise echocardiographic visualization of vegetations helps to stratify patients into a high-risk sub-group, perhaps warranting early prophylactic surgical intervention. Transoesophageal echocardiography may play an important role in assessing the clinical outcome for these patients.     

儿童感染性心内膜炎临床表现与治疗对策

目的分析儿童感染性心内膜炎的临床特征、治疗和预后。方法回顾性分析1998—2012年收治的83例感染性心内膜炎患儿的临床资料。结果共83例患儿,男53例、女30例,平均年龄(6.8±4.6)岁,临床特征以发热(77.1%)、轻中度贫血(71.1%)、C反应蛋白升高(67.5%)、红细胞沉降率增高(60.2%)、白细胞增高(47.0%)为主;出现栓塞症状20例(24.1%);血培养阳性56例(67.5%),以革兰阳性菌为主,链球菌属及葡萄球菌属占89.3%;万古霉素等敏感抗生素治疗有效;超声检查检出赘生物68例(82%)。55例(66.2%)患儿接受心脏手术,最终死亡7例(8.4%)。结论近年来感染性心内膜炎的病原菌变迁,缓症链球菌及金黄色葡萄球菌成为主要病原菌,需万古霉素等敏感抗生素治疗;心脏超声检出赘生物阳性率较高。     

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

Background: Aggregatibacter actinomycetemcomitans resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of A. actinomycetemcomitans by neutrophils. Methods: Killing assays were conducted in the presence of either 2 μg/mL AZM or 16 μg/mL AMX (equipotent against A. actinomycetemcomitans). Neutrophils were loaded by incubation with the appropriate antibiotic. Opsonized A. actinomycetemcomitans strain Y4 was incubated with the indicated antibiotic alone, with loaded neutrophils and antibiotic, or with control neutrophils (without antibiotic) at multiplicities of infection (MOIs) of 30 and 90 bacteria per neutrophil. Results: Neutrophil incubation with 2 μg/mL AZM yielded an intracellular concentration of 10 μg/mL. At an MOI of 30, neutrophils loaded with AZM failed to kill significantly more bacteria than control neutrophils during the 60‐ and 90‐minute assay periods. At an MOI of 90, neutrophils loaded with AZM killed significantly more bacteria than either AZM alone or control neutrophils during 60‐ and 90‐minute incubations (P <0.05), and killed significantly more bacteria after 90 minutes than the sum of the killing produced by AZM alone or neutrophils alone. Neutrophils incubated with AMX under identical conditions also killed significantly more bacteria than either AMX alone or control neutrophils, but there was no evidence of synergism between AMX and neutrophils. Conclusions: Neutrophils possess a concentrative transport system for AZM that may enhance killing of A. actinomycetemcomitans. Its effects are most pronounced when neutrophils are greatly outnumbered by bacteria.     

Contemporary management and outcomes of infective tunnelled haemodialysis catheter-related right atrial thrombi: a case series and literature review

INTRODUCTIONInfective haemodialysis catheter-related right atrial thrombus (CRAT) is a complication of tunnelled catheter use. Management recommendations are based mainly on published case series prior to 2011. We report our institution’s recent experience in managing infective haemodialysis CRAT and correlate treatment with outcomes.METHODSWe conducted a retrospective analysis of haemodialysis CRAT cases diagnosed on transthoracic echocardiography between 1 January 2011 and 31 December 2017. Clinical outcomes, including mortality at 180 days post diagnosis and thrombus resolution, were traced from electronic medical records.RESULTSThere were 14 cases identified. The median age was 59 (range 47–88) years and 11 (78.6%) were male. Sepsis was the most common reason for hospitalisation (71.4%). Blood cultures identified Staphylococcus aureus in seven cases, of which two were methicillin-resistant. Three had coagulase-negative Staphylococcus. All cases received antibiotics with infectious disease physician input. Seven were treated with catheter removal alone, of which three died within 180 days. Both cases treated with catheter removal plus anticoagulation survived at 180 days. Of the two cases who had anticoagulation without catheter removal, one died within 180 days and the other did not have thrombus resolution. Three underwent surgical thrombus removal, of which two died postoperatively and the last required repeated operations and prolonged hospitalisation. Mortality at 180 days post diagnosis was 42.9%.CONCLUSIONCatheter removal and anticoagulation are modestly effective. Surgery is associated with poor outcomes. Despite contemporary management, infective haemodialysis CRAT still results in high mortality. Prospective studies are needed to identify the optimal management.     

经食管三维超声心动图在主动脉瓣位感染性心内膜炎中的应用

目的 探讨经食管三维超声心动图（three-dimensional transesophageal echocardiography,3D-TEE）在诊断感染性心内膜炎（infective endocarditis,IE）主动脉瓣病变中的价值.方法 对49例通过经胸超声心动图（transthoracic echocardiography,TTE）与3D-TEE诊断IE主动脉瓣病变患者的超声诊断特点进行分析,以心脏外科术中所见为“金标准”,将超声特点（赘生物、瓣叶穿孔、瓣周脓肿）与手术结果进行对照.结果 3D-TEE对赘生物、瓣叶穿孔、瓣周脓肿诊出的敏感性及特异性均高于TTE,差异有统计学意义（P＜0.05）.对于检测长度＜（4.5±0.7）mm的赘生物,3D-TEE较TTE更加敏感,差异有统计学意义（P＜0.05）.对于检测瓣周脓肿,3D-TEE较TTE更加敏感,差异有统计学意义（P＜0.05）,且容易发现瓣周脓肿早期组织水肿的情况.结论 与TTE相比较,3D-TEE能更准确检测IE主动脉瓣病变,有效评价此类患者瓣周脓肿情况,具有重要的临床应用价值.