Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Clinical variation in the early assessment and management of suspected community-acquired meningitis: a multicentre retrospective study.

BACKGROUND: Bacterial meningitis is a medical emergency and timely management has been shown to improve outcomes. The aim of this study was to compare the early assessment and management of adults with suspected community-onset meningitis between hospitals and identify opportunities for clinical practice improvement. METHODS: This retrospective cohort study was conducted at three principal referral hospitals in Sydney, Australia. Adult patients with suspected meningitis undergoing cerebrospinal fluid sampling between 1 July 2018 and 31 June 2019 were included. Relevant clinical and laboratory data were extracted from the medical record. Differences between sites were analysed and factors associated with time to antimicrobial therapy were assessed by Cox regression. RESULTS: In 260 patients, the median time from triage to antibiotic administration was 332 min with a difference of up to 147 min between hospitals. Median time from triage to lumbar puncture (LP) was 366 min with an inter-hospital difference of up to 198 min. Seventy per cent of patients had neuroimaging prior to LP, and this group had a significantly longer median time to antibiotic administration (367 vs 231 min; P = 0.001). Guideline concordant antibiotics were administered in 84% of patients, with only 39% of those administered adjunctive corticosteroids. Seven (3%) patients had confirmed bacterial meningitis. Modifiable factors associated with earlier antimicrobial administration included infectious diseases involvement (adjusted hazard ratio [aHR], 1.50 [95% confidence interval (CI), 1.01-2.24]) and computed tomography (CT) scanning (aHR, 0.67 [95% CI, 0.46-0.98]). CONCLUSION: Opportunities for improvement include reducing the time to LP and antibiotic administration, improving coadministration of corticosteroids and avoiding potentially unnecessary CT scanning.

Evaluation of the World Health Organization Global Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network's Laboratory External Quality Assessment Programme, 2014-2019.

Introduction. In 2009, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine Preventable Disease (IB-VPD) Surveillance Network (GISN) to monitor the global burden and aetiology of bacterial meningitis, pneumonia and sepsis caused by Haemophilus influenzae (Hi), Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp).Hypothesis/Gap Statement. The GISN established an external quality assessment (EQA) programme for the characterization of Hi, Nm and Sp by culture and diagnostic PCR.Aim. To assess the performance of sentinel site laboratories (SSLs), national laboratories (NLs) and regional reference laboratories (RRLs) between 2014 and 2019 in the EQA programme.Methodology. Test samples consisted of bacterial smears for Gram-staining, viable isolates for identification and serotyping or serogrouping (ST/SG), plus simulated cerebrospinal fluid (CSF) samples for species detection and ST/SG by PCR. SSLs and NLs were only required to analyse the slides for Gram staining and identify the species of the live isolates. RRLs, and any SLs and NLs that had the additional laboratory capacity, were also required to ST/SG the viable isolates and analyse the simulated CSF samples.Results. Across the period, 69-112 SS/NL labs and eight or nine RRLs participated in the EQA exercise. Most participants correctly identified Nm and Sp in Gram-stained smears but were less successful with Hi and other species. SSLs/NLs identified the Hi, Nm and Sp cultures well and also submitted up to 56 % of Hi, 62 % of Nm and 33 % of Sp optional ST/SG results each year. There was an increasing trend in the proportion of correct results submitted over the 6 years for Nm and Sp. Some SSLs/NLs also performed the optional detection and ST/SG of the three organisms by PCR in simulated CSF from 2015 onwards; 89-100 % of the CSF samples were correctly identified and 76-93 % of Hi-, 90-100 % of Nm- and 75-100 % of Sp-positive samples were also correctly ST/SG across the distributions. The RRLs performed all parts of the EQA to a very high standard, with very few errors across all aspects of the EQA.Conclusion. The EQA has been an important tool in maintaining high standards of laboratory testing and building of laboratory capacity in the GISN.

Accurate, fast and cost-effective simultaneous detection of bacterial meningitis by qualitative PCR with high-resolution melting.

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are leading causes of meningitis and acute invasive infections. PCR-based methods are widely used for the diagnosis and surveillance of bacterial pathogens because of their high sensitivity, specificity and high-throughput capabilities compared with conventional laboratory methods. This study evaluated a high-resolution melting qualitative PCR analysis method for the simultaneous detection of these three pathogens. The assay has been optimized to detect three species-specific genes of each organism isolated from clinical samples, enabling accurate identification of the etiological agent. The method proved to be highly sensitive and cheaper than the real-time PCR TaqMan® system because it is probe-free; it could be used for the diagnosis of invasive diseases in public health laboratories of developing countries.

The Cost of Suspected and Confirmed Bacterial Meningitis Cases Treated at Jimma University Medical Center, Ethiopia.

Background: Infections of the central nervous system (CNS) such as meningitis or encephalitis can be caused by myriad of microorganisms and may be life-threatening. In Ethiopia, it is an important cause of premature death and disability, being the 9th most common cause of years of life lost and loss of disability-adjusted life years.The objective of this study was to estimate the cost of suspected and confirmed bacterial meningitis among inpatient managed patients at JUMC. Methods: A facility-based cross-sectional study was conducted from July 28 to September 12, 2018. A semi-structured questionnaire was used in this study. Checklists were used to collect the types of laboratory tests performed and prescribed medications. This cost of illness study was conducted from the patient perspectives. We employed a micro-costing bottom-up approach to estimate the direct cost of meningitis. The human capital approach was used for estimating wages lost. Result: Among total patients admitted and treated in JUMC, higher proportions (69.8%) were suspected bacterial meningitis but have been treated as confirmed cases. Total median costs for both suspected and confirmed bacterial meningitis patients were estimated to be ETB 98,812.32 (US $ 3,593.2; IQR 1,303.0 to 5,734.0). Total median direct cost was ETB 79,248.02 (US $ 2,881.75; IQR 890.7 to 3,576.7). Moreover, 45.3% of the patients reported that they were either admitted or given medication at JUMC or nearby health facility before their current admissions. Conclusion: These findings indicate that most cases of bacterial meningitis were treated only empirically, and the cost of the treatment was high, especially for resource-limited countries like Ethiopia. To minimize the burden of meningitis and avoid unnecessary hospitalizations, the availability of diagnostic techniques is vitally important.

Risk-stratification in febrile infants 29 to 60 days old: a cost-effectiveness analysis.

BACKGROUND: Multiple clinical prediction rules have been published to risk-stratify febrile infants ≤60 days of age for serious bacterial infections (SBI), which is present in 8-13% of infants. We evaluate the cost-effectiveness of strategies to identify infants with SBI in the emergency department. METHODS: We developed a Markov decision model to estimate outcomes in well-appearing, febrile term infants, using the following strategies: Boston, Rochester, Philadelphia, Modified Philadelphia, Pediatric Emergency Care Applied Research Network (PECARN), Step-by-Step, Aronson, and clinical suspicion. Infants were categorized as low risk or not low risk using each strategy. Simulated cohorts were followed for 1 year from a healthcare perspective. Our primary model focused on bacteremia, with secondary models for urinary tract infection and bacterial meningitis. One-way, structural, and probabilistic sensitivity analyses were performed. The main outcomes were SBI correctly diagnosed and incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: In the bacteremia model, the PECARN strategy was the least expensive strategy ($3671, 0.779 QALYs). The Boston strategy was the most cost-effective strategy and cost $9799/QALY gained. All other strategies were less effective and more costly. Despite low initial costs, clinical suspicion was among the most expensive and least effective strategies. Results were sensitive to the specificity of selected strategies. In probabilistic sensitivity analyses, the Boston strategy was most likely to be favored at a willingness-to-pay threshold of $100,000/QALY. In the urinary tract infection model, PECARN was preferred compared to other strategies and the Boston strategy was preferred in the bacterial meningitis model. CONCLUSIONS: The Boston clinical prediction rule offers an economically reasonable strategy compared to alternatives for identification of SBI.

Trends in Management of Simple Febrile Seizures at US Children's Hospitals.

OBJECTIVE: We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS: In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS: We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS: Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.

Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree.

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.

Otoacoustic emissions in patients with bacterial meningitis.

Objective: Systematic evaluation of studies using otoacoustic emissions (OAEs) to monitor cochlear damage in patients with bacterial meningitis.Design: Systematic review. This includes articles retrieved from PUBMED and EMBASE. The search-strategy was based on the PICO-model. Data processing involved Cochrane Public Health Data Extraction template in addition to assessment of risk of bias and applicability with the Second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.Study samples: Thirty-eight articles were identified with 6 studies comprising 391 children and 17 adult patients eligible for full assessment.Results: Studies were heterogenic and the timing of OAE was incomparable between studies. The frequency of severe loss of hearing was reported to occur between 1.6 and 21% of the patients with culture-proven meningitis. The included studies, albeit heterogenic, found OAE-screening feasible and sensitive in children recovering from bacterial meningitis.Conclusion: No children with hearing loss were reported to pass an OAE screening in any of the included studies. The timing, sensitivity and extent of sensorineural hearing loss determined by OAE could not be assessed from the included studies. Levels of risk of bias were inconsistent and the clinical feasibility for routine inclusion of patients with bacterial meningitis was uncertain. The technological development within this field implies the need for further research.

New molecular tools for meningitis diagnostics in Ethiopia - a necessary step towards improving antimicrobial prescription.

BACKGROUND: Meningitis remains a top cause of premature death and loss of disability-adjusted life years in low-income countries. In resource-limited settings, proper laboratory diagnostics are often scarce and knowledge about national and local epidemiology is limited. Misdiagnosis, incorrect treatment and overuse of antibiotics are potential consequences, especially for viral meningitis. METHODS: A prospective study was conducted over three months in a teaching hospital in Ethiopia with limited laboratory resources. Cerebrospinal fluid (CSF) samples from patients with suspected meningitis were analysed using a multiplex PCR-based system (FilmArray, BioFire), in addition to basic routine testing with microscopy and culture. Clinical data, as well as information on treatment and outcome were collected. RESULTS: Two hundred and eighteen patients were included; 117 (54%) neonates (0-29 days), 63 (29%) paediatrics (1 month-15 years) and 38 (17%) adults (≥16 years). Of 218 CSF samples, 21 (10%) were PCR positive; 4% in neonates, 14% in paediatrics and 18% in adults. Virus was detected in 57% of the PCR positive samples, bacteria in 33% and fungi in 10%. All CSF samples that were PCR positive for a bacterial agent had a white cell count ≥75 cells/mm3 and/or turbid appearance. The majority (90%) of patients received more than one antibiotic for treatment of the meningitis episode. There was no difference in the mean number of different antibiotics received or in the cumulative number of days with antibiotic treatment between patients with a microorganism detected in CSF and those without. CONCLUSIONS: A rapid molecular diagnostic system was successfully implemented in an Ethiopian setting without previous experience of molecular diagnostics. Viral meningitis was diagnosed for the first time in routine clinical practice in Ethiopia, and viral agents were the most commonly detected microorganisms in CSF. This study illustrates the potential of rapid diagnostic tests for reducing antibiotic usage in suspected meningitis cases. However, the cost of consumables for the molecular diagnostic system used in this study limits its use in low-income countries.

Assessment of acute headache in adults - what the general physician needs to know.

Headache is common. Up to 5% of attendances to emergency departments and acute medical units are due to headache. Headache is classified as either primary (eg migraine, cluster headache) or secondary to another cause (eg meningitis, subarachnoid haemorrhage). Even in the acute setting the majority of cases are due to primary causes. The role of the attending physician is to take a comprehensive history to diagnose and treat benign headache syndromes while ruling out sinister aetiologies. This brief article summarises the approach to assessment of headache presenting in acute and emergency care.

Epidemiology of Meningitis in Oman-Implications for Future Surveillance.

OBJECTIVES: This study aimed to understand the epidemiology of meningitis cases admitted to hospitals in Oman and to identify any changing microbial patterns from the introduction of the new vaccines. METHODS: A retrospective analysis of all cases of meningitis reported through a national surveillance system. Meningitis is a notifiable disease. RESULTS: Of a total of 581 cases of meningitis from the period between January 1, 2005 and December 31, 2013, 15% (88) were confirmed to be bacterial in origin and 7.2% (42/581) viral. In 50.9% (296) of patients with suspected pyogenic meningitis, no specific bacterial pathogen were identified, and in 26% of cases (151) a cerebrospinal fluid study could not be undertaken. Among 88 cases with confirmed bacterial pathogens the organisms identified were Streptococcus pneumoniae (65.9%), Neisseria meningitides (18.2%), Haemophilus influenzae (6.8%), and other organisms (9.1%). The peak incidence was in children <2 years of age (39.4%). It showed notable decline in H. influenzae cases as well as pneumococcal meningitis cases, possibly indicative of the successful immunization program. CONCLUSION: A drop in H. Influenzae and pneumococcal meningitis cases was possibly the effect of the introduction of vaccines. It shows the need for improving diagnostic accuracy, laboratory capacities, and quality of surveillance reporting.

Need for Lumbar Puncture in Children Younger Than 12 Months Presenting With Simple Febrile Seizure.

OBJECTIVES: Recently, conflicting results have been reported regarding the necessity of routine lumbar puncture in children less than 12 months of age with simple febrile seizure. The aims of this study were to evaluate the results of lumbar puncture in children younger than 60 months of age with febrile seizure and to reassess the need for lumbar puncture in children younger than 12 months with simple febrile seizure. METHODS: A retrospective chart review was performed in patients younger than 60 months who presented with febrile seizure and underwent lumbar puncture from January 2005 to January 2015. RESULTS: A total of 1249 patients presenting with febrile seizure were admitted. Of these, 816 met inclusion criteria for presenting with simple febrile seizure. Lumbar puncture was performed in 75 patients (9.2%; age, mean ± SD, 12.05 ± 9.13 months; male/female, 31/44), who were reviewed. Sixty-six (88.0%) of 75 patients were younger than 12 months. Five patients (6.7%) showed pleocytosis in cerebrospinal fluid, and 4 of them were younger than 1 year of age. Three patients (4.0%) had bacterial meningitis and were 4, 8, and 12 months. Streptococcus pneumoniae (2 patients) and Klebsiella pneumoniae (1 patient) were isolated in cerebrospinal fluid. Nobody had neurologic signs suggesting bacterial meningitis, and all of them completed scheduled immunizations and were up-to-date. CONCLUSION: Lumbar puncture should be considered in every child younger than 12 months of age with a simple febrile seizure owing to lack of abnormal neurologic sign even if immunization is up-to-date.

Diagnostic Value of the Leukocyte Esterase Test for Early Detection of Pleocytosis in Cerebrospinal Fluid of Patients with Suspected Acute Bacterial Meningitis.

BACKGROUND: Rapid and accurate diagnosis of patients with suspected bacterial meningitis (BM) is crucial to prevent potential subsequent mortality and morbidity. The aim of this study was to explore the diagnostic value of the rapid leukocyte esterase (LE) strip test in identifying pleocytosis in cerebrospinal fluid (CSF) samples of patients with suspected BM. METHODS: A total of 126 patients with suspected meningitis were enrolled in this prospective study. Microscopic examination (cell count and differential) and leukocyte esterase (LE) rapid strip test were performed on cerebrospinal fluid (CSF) samples. Sensitivity, specificity, positive predictive value and negative predictive value of the LE test were determined. RESULTS: Fifty-two patients (41%) had pleocytosis in the CSF, while 48 (38%) patients had a positive rapid LE strip test result. The diagnostic accuracy of this test for pleocytosis was translated to a sensitivity of 84.6% (95%CI 71.9, 93.1) and a specificity of 94.5% (95%CI 86.7, 98.5), with an area under the receiver operating curve of 0.88. CONCLUSION: The LE strip test, through rapid and accurate determination of CSF pleocytosis, could be considered as an additional test in the diagnosis of bacterial meningitis. It can be tested at bedside and is feasible to do in resource-limited settings.

Cranial Imaging Before Lumbar Puncture in Adults With Community-Acquired Meningitis: Clinical Utility and Adherence to the Infectious Diseases Society of America Guidelines.

BACKGROUND.: The Infectious Diseases Society of America (IDSA) guidelines delineate criteria for the use of computed tomography (CT) scan of the head before lumbar puncture (LP) in adults with community-acquired meningitis (CAM). There are limited data to document adherence to these guidelines and assess the clinical utility of brain imaging. METHODS.: This was a retrospective analysis from January 2005 to January 2010 in Houston, Texas. RESULTS.: Among 614 adults with CAM, 407 patients (66.3%) did not have an indication for a head CT scan and 207 (33.7%) did. Patients with a CT scan indication were older, had more comorbidities, were sicker, and had more urgent treatable etiologies and adverse clinical outcomes (P < .001). A CT scan was ordered before the LP in 549 patients (89%). Overall, clinicians did not adhere to clinical guidelines in 368 of 614 (60%) subjects. A CT of the head was ordered when not indicated in 355 of 549 patients (64%), and not done when indicated in 13 of 207 patients (0.6%). CT of the head revealed intracranial abnormalities in 35 of 193 patients (18.1%) with an indication for brain imaging, compared with only 2 of 356 (0.05%) with no indication (P < .05). Major intracranial findings were seen in only 15 of 549 (2.7%) patients, all with an indication for brain imaging. Furthermore, only 8 patients had abnormalities that affected clinical management. CONCLUSIONS.: Most clinicians do not adhere to IDSA guidelines, delaying diagnostic LP and increasing costs. Usefulness of head CT in patients with CAM without an indication for imaging is limited and has no impact in clinical management.

Do All Children Who Present With a Complex Febrile Seizure Need a Lumbar Puncture?

STUDY OBJECTIVE: We assess the prevalences of bacterial meningitis and herpes simplex virus meningoencephalitis (HSV-ME) in children with a complex febrile seizure and determine these prevalences in the subgroup of children with a clinical examination result not suggestive of meningitis or encephalitis. METHODS: This multicenter retrospective study was conducted in 7 pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 months to 5 years for a complex febrile seizure from January 2007 to December 2011 were analyzed. We defined a subgroup of patients whose clinical examination result was not suggestive of meningitis or encephalitis. Bacterial meningitis and HSV-ME were sequentially sought for by analyzing bacteriologic and viral data at the visit, looking for data from a second visit to the hospital after the index visit, and telephoning the child's parents. RESULTS: From a total of 1,183,487 visits in the 7 pediatric EDs, 839 patients presented for a complex febrile seizure, of whom 260 (31.0%) had a lumbar puncture. The outcomes bacterial meningitis and HSV-ME were ascertainable for 715 (85%) and 657 (78.3%) visits, respectively, and we found 5 cases of bacterial meningitis (0.7% [95% confidence interval [CI] 0.2% to 1.6%]) and no HSV-ME (0% [95% CI 0% to 0.6%]). Among the 630 visits of children with a clinical examination result not suggesting meningitis or encephalitis, we found no bacterial meningitis (0% [95% CI 0% to 0.7%]) and no HSV-ME (0% [95% CI 0% to 0.8%]). CONCLUSION: In children with a complex febrile seizure, bacterial meningitis and HSV-ME are unexpected events when the clinical examination after complex febrile seizure is not suggestive of meningitis or encephalitis.

Validation of the "Step-by-Step" Approach in the Management of Young Febrile Infants.

BACKGROUND: A sequential approach to young febrile infants on the basis of clinical and laboratory parameters, including procalcitonin, was recently described as an accurate tool in identifying patients at risk for invasive bacterial infection (IBI). Our aim was to prospectively validate the Step-by-Step approach and compare it with the Rochester criteria and the Lab-score. METHODS: Prospective study including infants ≤90 days with fever without source presenting in 11 European pediatric emergency departments between September 2012 and August 2014. The accuracy of the Step-by-Step approach, the Rochester criteria, and the Lab-score in identifying patients at low risk of IBI (isolation of a bacterial pathogen in a blood or cerebrospinal fluid culture) was compared. RESULTS: Eighty-seven of 2185 infants (4.0%) were diagnosed with an IBI. The prevalence of IBI was significantly higher in infants classified as high risk or intermediate risk according to the Step by Step than in low risk patients. Sensitivity and negative predictive value for ruling out an IBI were 92.0% and 99.3% for the Step by Step, 81.6% and 98.3% for the Rochester criteria, and 59.8% and 98.1% for the Lab-score. Seven infants with an IBI were misclassified by the Step by Step, 16 by Rochester criteria, and 35 by the Lab-score. CONCLUSIONS: We validated the Step by Step as a valuable tool for the management of infants with fever without source in the emergency department and confirmed its superior accuracy in identifying patients at low risk of IBI, compared with the Rochester criteria and the Lab-score.

Specific detection of common pathogens of acute bacterial meningitis using an internally controlled tetraplex-PCR assay.

Accurate and timely diagnosis of acute bacterial meningitis is critical for antimicrobial treatment of patients. Although PCR-based methods have been widely used for the diagnosis of acute meningitis caused by bacterial pathogens, the main disadvantage of these methods is their high cost. This disadvantage has hampered the widespread use of molecular assays in many developing countries. The application of multiplex assays and "in-house" protocols are two main approaches that can reduce the overall cost of a molecular test. In the present study, an internally controlled tetraplex-PCR was developed and validated for the specific detection of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in cerebrospinal fluid (CSF) samples. The analysis of a panel of other human pathogens showed no cross-reactivity in the assay. The analytical sensitivity of the in-house assay was 792.3 copies/ml, when all three bacteria were presentin the specimens. This value was calculated as 444.5, 283.7, 127.8 copies/ml when only S. pneumoniae, N. meningitidis and H. influenzae, respectively, were present. To demonstrate the diagnostic performance of the assay, a total of 150 archival CSF samples were tested and compared with a commercial multiplex real-time PCR kit. A diagnostic sensitivity of 92.8% and a specificity of 95.1% were determined for the present tetraplex-PCR assay. The results indicate that the established method is sensitive, specific and cost-effective, and can be used particularly in situations where the high cost of commercial kits prevents the use of molecular methods for the diagnosis of bacterial meningitis.

Following the (Clinical Decision) Rules: Opportunities for Improving Safety and Resource Utilization With the Bacterial Meningitis Score.

BACKGROUND: The Bacterial Meningitis Score accurately classifies children with cerebrospinal fluid (CSF) pleocytosis at very low risk (VLR) versus not very low risk (non-VLR) for bacterial meningitis. Most children with CSF pleocytosis detected during emergency department evaluation are hospitalized despite the high accuracy of this prediction rule and the decreasing incidence of bacterial meningitis. The lack of widespread use of this rule may contribute to unnecessary risk exposure and costs. METHODS: This cross-sectional study included 1049 patients who, between January 2010 and May 2013, had suspicion for meningitis and underwent both a complete blood cell count and CSF studies during their emergency department evaluation. We then examined their hospitalizations to characterize exposure to drugs, radiologic studies, and the costs associated with their care to determine the safety and value repercussions of these VLR admissions. Primary outcomes include duration of antibiotics, exposure to drugs and radiology studies, safety events, and costs incurred during these VLR admissions. RESULTS: Twenty patients classified as VLR were admitted to the hospital. On average they received 35 hours of antibiotic therapy. There was 1 adverse drug event and 1 safety event. CONCLUSIONS: The VLR patients admitted to the hospital were exposed to risk and costs despite their low risk stratification. Systematic application of the Bacterial Meningitis Score could prevent these exposures and costs.