Passive exposure to tobacco smoke and bacterial meningitis in children

OBJECTIVE: To determine whether an association exists between passive exposure to tobacco smoke and bacterial meningitis in childhood, in an Australian population. METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of 71 children admitted to the Women's and Children's Hospital, North Adelaide, with bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of Haemophilus influenzae type b (Hib) meningitis decreased significantly during the study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99, Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test; P < 0.001). Although comparable numbers of cases and controls came from smoking families (41% vs 45%), more cases came from bi-parental smoking households (17% vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases were more likely to live in households where parents smoked inside (27% vs 13%; OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had had meningitis were significantly more likely to have parents who smoked inside the house, than children who had not had meningitis (66% vs 28%, Fisher's exact test; P = 0.005). CONCLUSION: This study suggests there may be an association between high levels of passive exposure to tobacco smoke and bacterial meningitis in Australian children. A study with larger numbers of affected children which quantifies passive exposure to tobacco smoke is needed to determine the strength of this association.     

消毒供应室下送工作在控制院内感染中的作用

目的:严格下送下收程序,使下送无菌物品不受到污染,达到控制院内感染,减少交叉感染,从而提高医院整体医疗质量。方法:做好下送、回收车的管理,清洁消毒,专车专用和下送护士手的清洁与分发无菌物品的程序,每周进行二次抽查进行细菌培养。结果:每周下送车内的细菌菌落数均≤5cfu/cm3,符合无菌物品放置的标准要求;手的细菌菌落数在≤5cfu/cm3,符合II类区域工作人员手的要求。结论:严格要求下送车辆的清洁消毒、专车专用和下送工作人员手的清洁,有助于减少消毒物品受到污染的机会,防止交叉感染,可有效控制医院内的感染发生。     

Postradiation lumbosacral radiculopathy with spinal root cavernomas mimicking carcinomatous meningitis

Lumbosacral radiculopathy is a rare complication of radiotherapy and may be challenging to differentiate from diagnosis of a tumor recurrence. We reviewed the records of three patients with a past history of cancer and radiotherapy who were referred for suspicion of carcinomatous meningitis on lumbar MRI, but whose final diagnosis was radiation-induced lumbosacral radiculopathy. The three patients developed a progressive lumbosacral radiculopathy at 20, 13, and 47 years after lumbar radiotherapy delivered for renal cancer, Hodgkin's disease, and a seminoma, respectively. MRI showed a diffuse, nodular enhancement of the cauda equina nerve roots on T1 sequences, suggestive of leptomeningeal metastasis. A slowly progressive clinical course over several years and negative cerebrospinal fluid cytologic analysis ruled out the diagnosis of carcinomatous meningitis. Because of the radiologic findings, a biopsy was performed in two patients. In the first, a biopsy limited to the arachnoid excluded a malignant infiltration. In the second, a biopsy of the enhancing lesions demonstrated spinal root cavernomas. These observations, together with three recent case reports in the literature, delineate a syndrome of "radiationinduced lumbosacral radiculopathy with multiple spinal root cavernomas" that mimics carcinomatous meningitis on MRI. Its diagnosis is important in order to avoid inappropriate treatment and useless or dangerous spinal root biopsies.     

A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.     

Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis

Matrix metalloproteinases (MMPs) are a family of Zn²⁺-dependent endopeptidases targeting extracellular matrix (ECM) compounds as well as a number of other proteins. Their proteolytic activity acts as an effector mechanism of tissue remodeling in physiologic and pathologic conditions, and as modulator of inflammation. In the context of neuro-inflammatory diseases, MMPs have been implicated in processes such as (a) blood–brain barrier (BBB) and blood–nerve barrier opening, (b) invasion of neural tissue by blood-derived immune cells, (c) shedding of cytokines and cytokine receptors, and (d) direct cellular damage in diseases of the peripheral and central nervous system. This review focuses on the role of MMPs in multiple sclerosis (MS) and bacterial meningitis (BM), two neuro-inflammatory diseases where current therapeutic approaches are insufficient to prevent severe disability in the majority of patients. Inhibition of enzymatic activity may prevent MMP-mediated neuronal damage due to an overactive or deviated immune response in both diseases. Downregulation of MMP release may be the molecular basis for the beneficial effect of IFN-β and steroids in MS. Instead, synthetic MMP inhibitors offer the possibility to shut off enzymatic activity of already activated MMPs. In animal models of MS and BM, they efficiently attenuated clinical disease symptoms and prevented brain damage due to excessive metalloproteinase activity. However, the required target profile for the therapeutic use of this novel group of compounds in human disease is not yet sufficiently defined and may be different depending on the type and stage of disease. Currently available MMP inhibitors show little target-specificity within the MMP family and may lead to side-effects due to interference with physiological functions of MMPs. Results from human MS and BM indicate that only a restricted number of MMPs specific for each disease is up-regulated. MMP inhibitors with selective target profiles offer the possibility of a more efficient therapy of MS and BM and may enter clinical trials in the near future.     

Successful treatment with linezolid of meningitis complicated with subdural empyema in a 6-month-old boy

Recent findings have focused on the possible role of linezolid as a suitable candidate for the treatment of central nervous system infections. The linezolid treatment for meningitis was sporadically reported in adults but there was no report in children. Here, we present a 6-month-old boy with meningitis and subdural empyema which was unresponsive to more conventional agents but successfully treated with linezolid therapy. A previously healthy 6-month-old boy was referred to our clinic for deteriorating general condition with fever, vomiting and seizures. He had fever and tense-bulging anterior fontanelle. Based on his first cerebrospinal fluid (CSF) results, empirical antibiotic therapy for bacterial meningitis consisting of vancomycin and ceftriaxone was started. However, CSF culture yielded no micro-organisms but blood culture showed coagulase-negative Staphylococci. On the 7th day, he still had high fever and the erythrocyte sedimentation rate (ESR) and serum CRP levels had risen by 105 mm/h and 36.2 mg/dl, respectively. On 10th day, computerized cranial tomography showed bilateral frontoparietal subdural empyema. Purulent material was evacuated by burr hole, and gram stains of the material showed polymorphonuclear leukocytes and no microorganisms. Clinical and CSF findings of our case were, unresponsiveness to vancomycin, ceftriaxone and consecutive meropenem treatment while we still observed subdural empyema during these treatments. For this reason we started linezolid 10 mg/kg twice daily. Clinical signs improved dramatically, with both completely normal neurological findings and normalization of CSF and radiological findings. To the of our best knowledge, linezolid treatment of meningitis in children has not been reported previously. Clinical and CSF findings of our case were improved completely with linezolid treatment. Also, control cranial computerized tomography showed the total recovery of subdural empyema. Here we present the youngest case with meningitis which was successfully treated with linezolid treatment.     

Complications of chronic suppurative otitis media and their management

OBJECTIVE: The objective of this is to determine the incidence of otogenic complications of chronic suppurative otitis media (CSOM) and its management. STUDY DESIGN: The authors conducted a retrospective study. METHODS: The study was conducted at the tertiary referral and teaching hospital. An analysis was made about the clinical and operative findings, surgical techniques and approaches, the overall management and recovery of the patients. The data were then compared with the relevant and available literature. RESULTS: Of the 70 cases, 47 (67%) had a single complication, of which eight (11%) had intracranial and 39 (56%) had extracranial complications. Twenty-three (33%) had two or more complications. The commonly encountered intracranial complications were otitic meningitis, lateral sinus thrombosis, and cerebellar abscess, which were seen in 13 (19%), 10 (14%), and 6 (9%) cases, respectively. Among the extracranial complications, mastoid abscess, postauricular fistula, and facial palsy were encountered in 26 (37%), 17 (24%) and 10 (14%) patients, respectively. Surgeries were the main mode of treatment for these conditions. According to severity, we found four different types of the lateral sinus involvement. Three patients with otitic facial palsy failed to regain full facial function despite surgery. A total of nine patients with the diagnosis of otitic meningitis, lateral sinus thrombosis and interhemispheric abscess expired. It constituted the mortality rate of 13% in our study. CONCLUSION: CSOM complications, despite its reduced incidence, still pose a great challenge in developing countries as the disease present in the advanced stage leading to difficulty in management and consequently higher morbidity and mortality.     

Clinical decision rules to distinguish between bacterial and aseptic meningitis

Background

Clinical decision rules have been derived to distinguish between bacterial and aseptic meningitis in the emergency room to avoid unnecessary antibiotic treatments and hospitalisations.

Aims

To evaluate the reproducibility and to compare the diagnostic performance of five clinical decision rules.

Methods

All children hospitalised for bacterial meningitis between 1995 and 2004 or aseptic meningitis between 2000 and 2004 have been included in a retrospective cohort study. Sensitivity and specificity were calculated by applying each rule to the patients. The best rule was a priori defined as the one yielding 100% sensitivity for bacterial meningitis, the highest specificity, and the greatest simplicity for a bedside application.

Results

Among the 166 patients included, 20 had bacterial meningitis and 146 had aseptic meningitis. Although three rules achieved 100% sensitivity (95% CI 84–100), one had a significantly lower specificity (13%, 95% CI 8–19) than those of the other two rules (57%, 95% CI 48–65; and 66%, 95% CI 57–73), which were not statistically different. The ease of manual computation of the rule developed by Nigrovic et al (a simple list of five items: seizure, blood neutrophil count, cerebrospinal fluid (CSF) Gram stain, CSF protein, CSF neutrophil count) was higher than the one developed by Bonsu and Harper.

Conclusion

On our population, the rule derived by Nigrovic et al had the best balance between accuracy and simplicity of manual computation and could help to avoid two thirds of unnecessary antibiotic treatments and hospitalisations.     

Rapid sterilisation of cerebrospinal fluid in meningococcal meningitis: Implications for treatment duration

AIM: The aim of this study was to determine the time and total cumulative dose of parenteral antibiotic, required to sterilize the cerebrospinal fluid (CSF) of children presenting with meningococcal meningitis (MM). METHODS: The study was a retrospective audit of children aged 0-14 years who presented between January 1995 and December 1999 with MM. All cases had a delayed lumbar puncture (LP) at least 1 h after commencing antibiotic therapy and demonstrated at least one of the following: (i) a positive CSF culture of Neisseria meningitidis (n = 6); (ii) Gram negative diplococci on Gram stain (n = 16) or (iii) a positive CSF plasma clearance rate test for N. meningitidis (n = 26). RESULTS: Forty-eight children were identified with a mean age of 4.4 years. The cumulative dose of antibiotic prior to LP, ranged from 22 to 440 mg/kg body weight. All cases (n = 24) who received a cumulative dose of at least 150 mg/kg of antibiotic, prior to LP, had a sterile CSF. No CSF taken more than 5 h after commencing antibiotics grew N. meningitidis. CONCLUSIONS: Children in this study with MM had rapid sterilisation of the CSF in less than 6 h. This would support recent recommendations to reduce the duration of antibiotic therapy to 4 days. There is however, lack of long-term data on sequelae with 4 days of treatment.