A prospective pilot study of gut microbiome in cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

A recent systematic review indicated that gut-microbiota-brain axis contributes to growth and rupture of intracranial aneurysms. However, gaps were detected in the role of intestinal microbiome in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). This is the first pilot study aiming to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case-control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as [Clostridium] innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = - 0.63; - 0.57, and - 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, we prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH.

Multidrug-resistant organisms (MDROs) in patients with subarachnoid hemorrhage (SAH).

Patient care in a neurointensive care unit (neuro-ICU) is challenging. Multidrug-resistant organisms (MDROs) are increasingly common in the routine clinical practice. We evaluated the impact of infection with MDROs on outcomes in patients with subarachnoid hemorrhage (SAH). A single-center retrospective analysis of SAH cases involving patients treated in the neuro-ICU was performed. The outcome was assessed 6 months after SAH using the modified Rankin Scale [mRS, favorable (0-2) and unfavorable (3-6)]. Data were compared by matched-pair analysis. Patient characteristics were well matched in the MDRO (n = 61) and control (n = 61) groups. In this center, one nurse was assigned to a two-bed room. If a MDRO was detected, the patient was isolated, and the nurse was assigned to the patient infected with the MDRO. In the MDRO group, 29 patients (48%) had a favorable outcome, while 25 patients (41%) in the control group had a favorable outcome; the difference was not significant (p > 0.05). Independent prognostic factors for unfavorable outcomes were worse status at admission (OR = 3.1), concomitant intracerebral hematoma (ICH) (OR = 3.7), and delayed cerebral ischemia (DCI) (OR = 6.8). Infection with MRDOs did not have a negative impact on the outcome in SAH patients. Slightly better outcomes were observed in SAH patients infected with MDROs, suggesting the benefit of individual care.

Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms.

Degeneration of intracranial aneurysm wall is under active research and recent studies indicate an increased risk of rupture of intracranial aneurysm among patients with periodontal diseases. In addition, oral bacterial DNA has been identified from wall samples of ruptured and unruptured aneurysms. These novel findings led us to evaluate if oral diseases could predispose to pathological changes seen on intracranial aneurysm walls eventually leading to subarachnoid hemorrhage. The aim of this review is to consider mechanisms on the relationship between periodontitis and aneurysm rupture, focusing on recent evidence.

[Presented with subarachnoid hemorrhage and then blood culture negative infective endocarditis: a case report and literature review].

The patient, a 43-year-old man, had paroxysmal headache three months ago, and he had complained the left occipital sharp pain, which could be alleviated by itself, with alalia and the right side of the upper limb numbness. Head computed tomography (CT) revealed a left temporal lobe intraparenchymal hemorrhage with the left side of the subarachnoid hemorrhage in small quantities. Digital subtraction angiography (DSA) revealed a suspicious aneurysm on the left internal carotid artery siphon. He had intermittent fever 1 month ago, with maximum body temperature 39 °C. He suffered headache again 20 days ago, with pain nature, duration and the way of easing up similar to the earlier onset. General examination demonstrated 2/6 grade blowing systolic murmurs at apex area. Neurological examination revealed that Babinski's sign was positive on the right side. Echocardiographic found an anterior mitral valve ve-getation on the 4th day in hospital. So his clinical diagnosis was infective endocarditis with cerebral embolism. He received vancomycin treatment immediately. His three blood cultures remained negative in hospital. His blood specimens were sent to Chinese Center for Disease Control and Prevention, indirect immunofluorescence method (IFA) IgG antibody detection revealed that the Bartonella henselae IgG antibody was positive. Therefore the clinical diagnosis was Bartonella endocarditis complicated with subarachnoid hemorrhage and cerebral embolism. Bartonella, an intracellular fastidious, gram-negative bacilli, was first documented as a cause of endocarditis in 1993 and since then has been increasingly recognized as an important etiology of infective culture-negative endocarditis. In cases of documented Bartonella endocarditis, the Infectious Diseases Society of America (IDSA) guidelines recommended 2 weeks of gentamicin plus 6 weeks of doxycycline treatment, to achieve a higher cure rate.

Nosocomial Infections and Antimicrobial Treatment in Coiled Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Nosocomial infections are common in patients with spontaneous subarachnoid hemorrhage (SAH). The aim of this retrospective cohort study was to determine the incidence of infections during SAH and to evaluate the course of inflammation parameters and its implications for long term outcome. OBJECTIVE: Ninety-nine consecutive coiled SAH patients were included. Laboratory and clinical parameters as well as culture positive infections were followed over the disease course. Long-term outcome was assessed at 6-month by the Glasgow Outcome score (GOS) and dichotomized in favorable (GOS>3) and unfavorable outcome (GOS≤3). RESULTS: The most frequent infections were pulmonary (30.3%) urinary tract (25.3%), blood stream infections (20.2%) and ventriculitis (5.1%). The incidence of infections did not significantly differ between outcome groups. In contrast, patients with unfavorable outcome had a higher incidence of sepsis (46.7% versus 24.6%). C-reactive protein (CRP) and leukocytes were significantly higher in patients with unfavorable outcome. A CRP increase of 6 mg/dl or more in the first 3 days after SAH was independently associated with unfavorable outcome (OR 7.19 CI 1.7-30.52; p=0.008). Patients with an early CRP increase were more frequently treated with antimicrobial therapy in the first 3 days after admission which led to a significantly lower incidence of culture positive infections in the later course. CONCLUSION: A sharp CRP-increase in the acute phase of SAH could potentially aid the intensivist in the early identification of patients at high risk for neurological morbidity. Early antimicrobial treatment reduces the rate of patients showing culture positive infections in the course of the disease.

Fatal complication of Legionella pneumophila pneumonia in a tocilizumab-treated rheumatoid arthritis patient.

We herein report a fatal case of Legionella pneumophila pneumonia in a tocilizumab-treated rheumatoid arthritis patient who was in a state of shock on admission but remained afebrile even during severe pneumonia. Legionella antigen was detected in the urine and neutrophil CD64 expression was highly elevated. Despite undergoing intensive treatment, the patient developed sepsis and died 12 days after admission. An autopsy indicated that while the Legionella infection had almost been controlled, a subarachnoid hemorrhage was the ultimate cause of death.

The connection between ruptured cerebral aneurysms and odontogenic bacteria.

BACKGROUND: Patients with ruptured saccular intracranial aneurysms have excess long-term mortality due to cerebrovascular and cardiovascular diseases compared with general population. Chronic inflammation is detected in ruptured intracranial aneurysms, abdominal aortic aneurysms and coronary artery plaques. Bacterial infections have been suggested to have a role in the aetiology of atherosclerosis. Bacteria have been detected both in abdominal and coronary arteries but their presence in intracranial aneurysms has not yet been properly studied. OBJECTIVE: The aim of this preliminary study was to assess the presence of oral and pharyngeal bacterial genome in ruptured intracranial aneurysms and to ascertain if dental infection is a previously unknown risk factor for subarachnoid haemorrhage. METHODS: A total of 36 ruptured aneurysm specimens were obtained perioperatively in aneurysm clipping operations (n=29) and by autopsy (n=7). Aneurysmal sac tissue was analysed by real time quantitative PCR with specific primers and probes to detect bacterial DNA from several oral species. Immunohistochemical staining for bacterial receptors (CD14 and toll-like receptor-2 (TLR-2)) was performed from four autopsy cases. RESULTS: Bacterial DNA was detected in 21/36 (58%) of specimens. A third of the positive samples contained DNA from both endodontic and periodontal bacteria. DNA from endodontic bacteria were detected in 20/36 (56%) and from periodontal bacteria in 17/36 (47%) of samples. Bacterial DNA of the Streptococcus mitis group was found to be most common. Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Treponema denticola were the three most common periodontal pathogens. The highly intensive staining of CD14 and TLR-2 in ruptured aneurysms was observed. CONCLUSIONS: This is the first report showing evidence that dental infection could be a part of pathophysiology in intracranial aneurysm disease.

Impact of antibiotic-impregnated catheters on the timing of cerebrospinal fluid infections in non-traumatic subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) has been recognized as a risk factor for ventriculostomy-related infections (VRI). In addition to the hemorrhagic cerebrospinal fluid (CSF), the potential need for prolonged catheterization may contribute to the increased CSF infection rate in this population. The use of antibiotic-impregnated catheters (AIC) has effectively reduced the risk of VRI. Herein, we examined specifically the impact of systematic insertion of AIC on the timing of CSF infections in SAH patients. METHODS: Retrospective review of patients admitted between April 2006 to March 2009 with a non-traumatic SAH who required an external ventriculostomy. Only patients with AIC were included. A meningitis or ventriculitis was diagnosed according to the published criteria of the Center for Disease Control and Prevention. RESULTS: This study includes 75 patients in which 97 drains were inserted. Seven infections (7/75 = 9.3%) occurred over 1,024 drainage days (DD), resulting in a rate of 6.8 infections/1,000 DD. The mean drainage time was 15.4 days in the infected AIC group compared with 10.2 days in the non-infected AIC group. No infection occurred before day 9 of drainage and 71% (5/7) occurred after more than 2 weeks of drainage. The observed timing of infections is delayed in comparison with that reported in series using non-AIC, which typically occur prior to the 10th day of drainage. CONCLUSIONS: In the high-risk population of non-traumatic SAH, the use of AIC delays the occurrence of infection compared with that reported with non-antibiotic-impregnated catheters. This may orient management strategies in SAH patients requiring a ventriculostomy.

Fatal subarachnoid hemorrhage caused by Aspergillus arteritis without angiographic abnormalities.

No source of bleeding is detected by angiogram in 15-20% of patients with nonaneurysmal subarachnoid hemorrhage (SAH). This negative angiographic finding might suggest a benign prognosis. We describe a case of fatal SAH caused by Aspergillus arteritis without formation of fusiform dilatation or aneurysms. A 76-year-old man with a 2-month history of progressive visual loss due to pachymeningitis around the optic nerves suffered from SAH in the bilateral sylvian fissures. Repetitive serum galactomannan assay and angiography showed no abnormality. Post mortem examination revealed marked proliferation of Aspergillus in the granulomas of the frontal base dura mater. In addition, major trunks and several branches of the bilateral middle cerebral arteries were invaded by Aspergillus hyphae, which destroyed the walls in the absence of dilatation and aneurysms. Invasive aspergillosis of the CNS often forms a mycotic aneurysm. However, four autopsy cases of nonaneurysmal SAH due to invasive aspergillosis have been reported. The present case is the second autopsy case of Aspergillus arteritis without angiographic abnormality, resulting in fatal SAH. Aggressive and continuous antifungal therapy is absolutely necessary in suspected cases of invasive aspergillosis of the CNS, even if angiography is negative and therapeutic markers of aspergillosis are normal.

Clinical experience with linezolid for the treatment of neurosurgical infections

Introducción: Evaluar el uso clínico de linezolid en el tratamiento de las infecciones neuroquirúrgicas. Métodos: Estudio retrospectivo observacional de una cohorte de pacientes hospitalizados que recibieron linezolid para tratamiento de infecciones neuroquirúrgicas con cultivo positivo, desde Julio de 2004 a febrero de 2009 en un hospital terciario español. Resultados: En el estudio se incluyeron 17 pacientes. Las principales comorbilidades fueron una o más de las siguientes: hemorragia subaracnoidea o intraventricular (n= 8), tumor sólido neurológico (n= 7), corticoides (n= 9) e hidrocefalia ( n= 6). Ocho pacientes fueron sometidos a craneotomía y 14 tenían un drenaje ventricular externo (EVD) como factor predisponente de infección. La meningitis fue la infección más común (11; 64,7%), seguida de ventriculitis (4; 23,5%) y absceso cerebral (2; 11,8%). El principal agente causal fue Staphylococcus spp coagulasa negativa (13; 76,5%). Linezolid fue usado como tratamiento incicial en 8 episodios, tras fracaso en 6 y por otras razones en 3. La vía oral fue usada en 9 (52,9%) episodios, de forma inicial en 2 casos. La duración media del tratamiento fue de 26,5 días (rango 15-58). No se observaron efectos adversos. Dieciseís pacientes (94,1%) fueron considerados curados. Hubo una recurrencia. La estancia media en el hospital fue de 45,6 (rango 15-112) días y la duración media del seguimiento fue de 7,2 (rango 0,4-32) meses. No hubo muertes relacionadas con los episodios activos. Coclusiones: Linezolid fue principalmente indicado en las infecciones postquirúrgicas asociadas a EVD por Staphylococcus spp coagulasa negativa. Fue inicialmente usado en la mayoría de los casos. Una alta tasa de curación clínica fue observada y no se detectaron efectos adversos. Más de la mitad de los pacientes se beneficiaron de las ventajas de la vía oral(AU)

Objectives: We sought to evaluate the clinical use of linezolid for the treatment of neurosurgical infections. Methods: Retrospective observational study of a cohort of hospitalized patients who received linezolid for a culture-positive neurosurgical infection from July 2004 to February 2009 in a tertiary hospital in Spain. Results: Seventeen patients were included in the study. Main comorbidities among these patients included one or more of the following: subarachnoidal or intraventricular hemorrhage (n=8), solid neurological cancer (n=7), corticosteroids (n=9) and hydrocephalus (n=6). Eight patients underwent a craniotomy and fourteen patients had an external ventricular drainage (EVD) as predisposing factors for infection. Meningitis was the most common infection (11; 64.7%), followed by ventriculitis (4; 23.5%) and brain abscesses (2; 11.8%). The main causative organisms were coagulase-negative Staphylococcus spp. (13; 76.5%). Linezolid was used as the initial therapy in 8 episodes, after therapy failure in 6 and for other reasons in 3. The oral route was used in 9 (52.9%) episodes; linezolid was initiated orally in 2 cases. The mean duration of treatment was 26.5 days (range 15-58). No adverse events were reported. Sixteen (94.1%) patients were considered cured. There was one recurrence. The mean length of hospital stay was 45.6 (range 15-112) days and the mean duration of follow- up was 7.2 (range 0.4-32) months. No related deaths occurred during active episodes. Conclusions: Linezolid was mainly indicated in post-neurosurgical EVD-associated infections due to coagulase-negative Staphylococcus spp. It was used as initial therapy in most cases. A high rate of clinical cure was observed and no related adverse events were reported. More than half of the patients were benefited by the advantages of the oral route of administration(AU)

Multidrug-resistant Acinetobacter baumannii ventriculitis: successful treatment with intraventricular colistin.

Acinetobacter baumannii has emerged as an important nosocomial pathogen that can cause a multitude of severe infections. In neurosurgical patients the usual presentation is ventriculitis associated with external ventricular drainage. Carbapenems have been considered the gold standard for the treatment of Acinetobacter baumannii ventriculitis, but resistant isolates are increasing worldwide, reducing the therapeutic options. In many cases polymyxins are the only possible alternative, but their poor blood-brain barrier penetration could require them to be directly administered intraventricularly and clinical experience with this route is limited. We review the literature concerning intraventricular use of colistin (polymyxin E) for A. baumannii ventriculitis and add three cases successfully treated with this method. Our experience suggests that intraventricular colistin is a potentially effective and safe therapy for the treatment of multidrug-resistant A. baumannii central nervous system infections.

Cerebral microdialysis for detection of bacterial meningitis in aneurysmal subarachnoid hemorrhage patients: a cohort study.

INTRODUCTION: Bacterial meningitis (BM) is a severe complication in patients with aneurysmal subarachnoid haemorrhage (SAH). Clinical signs of meningitis are often masked by SAH-related symptoms, and routine cerebrospinal fluid (CSF) analysis fails to indicate BM. Microdialysis (MD) is a technique for monitoring cerebral metabolism in patients with SAH. A cohort study was performed to investigate the value of MD for the diagnosis of BM. METHODS: Retrospectively, 167 patients with SAH in an ongoing investigation on cerebral metabolism monitored by MD were analysed for the presence of BM and related MD changes. Diagnosis of BM was based on microbiological CSF culture or clinical symptoms responding to antibiotic treatment, combined with an increased CSF cell count and/or fever. Levels of MD parameters before and after diagnosis of BM were analysed and compared with the spontaneous course in controls. RESULTS: BM developed in 20 patients, of which 12 underwent MD monitoring at the time of diagnosis. A control group was formed using 147 patients with SAH not developing meningitis. On the day BM was diagnosed, cerebral glucose was lower compared with the value three days before (p = 0.012), and the extent of decrease was significantly higher than in controls (p = 0.044). A decrease in cerebral glucose by 1 mmol/L combined with the presence of fever >or= 38 degrees C indicated BM with a sensitivity of 69% and a specificity of 80%. CSF chemistry failed to indicate BM, but the cell count increased during the days before diagnosis (p < 0.05). CONCLUSIONS: A decrease in MD glucose combined with the presence of fever detected BM with acceptable sensitivity and specificity, while CSF chemistry failed to indicate BM. In patients with SAH where CSF cell count is not available or helpful, MD might serve as an adjunct criterion for early diagnosis of BM.

Brucella-related cerebral aneurysms/subarachnoidal hemorrhage: a short review featuring a case report.

Brucellosis is a multisystem disease that may present with a large spectrum of clinical manifestations. Only five cases of intracranial aneurysm formation and/or subarachnoidal hemorrhage associated with brucellosis have been reported. In this paper, we take the opportunity to review these reports and present a new case of basilar artery aneurysm and subarachnoidal hemorrhage due to brucellosis.

Non-malignant disease mortality in meat workers: a model for studying the role of zoonotic transmissible agents in non-malignant chronic diseases in humans.

BACKGROUND: Current research efforts have mainly concentrated on evaluating the role of substances present in animal food in the aetiology of chronic diseases in humans, with relatively little attention given to evaluating the role of transmissible agents that are also present. Meat workers are exposed to a variety of transmissible agents present in food animals and their products. This study investigates mortality from non-malignant diseases in workers with these exposures. METHODS: A cohort mortality study was conducted between 1949 and 1989, of 8520 meat workers in a union in Baltimore, Maryland, who worked in manufacturing plants where animals were killed or processed, and who had high exposures to transmissible agents. Mortality in meat workers was compared with that in a control group of 6081 workers in the same union, and also with the US general population. Risk was estimated by proportional mortality and standardised mortality ratios (SMRs) and relative SMR. RESULTS: A clear excess of mortality from septicaemia, subarachnoid haemorrhage, chronic nephritis, acute and subacute endocarditis, functional diseases of the heart, and decreased risk of mortality from pre-cerebral, cerebral artery stenosis were observed in meat workers when compared to the control group or to the US general population. CONCLUSIONS: The authors hypothesise that zoonotic transmissible agents present in food animals and their products may be responsible for the occurrence of some cases of circulatory, neurological and other diseases in meat workers, and possibly in the general population exposed to these agents.