Prognostic Factors for Japanese Adults With Acute Community-Acquired Bacterial Meningitis: A Retrospective Study.

Background This study aimed to determine if the cerebrospinal fluid (CSF) cell count is useful for predicting the infection severity or prognosis in Japanese adults with community-acquired bacterial meningitis. Methodology This study retrospectively evaluated the prognosis of patients diagnosed with community-acquired bacterial meningitis at our hospital from January 2004 to December 2021 using the modified Rankin scale (mRs) (Showa General Hospital; N = 39). Patients were classified into the following two groups: (i) favorable (mRs: 0-3) and (ii) unfavorable (mRs: 4-6). Eight factors were selected and compared with outcomes, and then two factors were evaluated from those, and a multivariate logistic regression was used to determine the significant variables. Results CSF cell count was observed to be associated with poor prognoses (odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.99995-0.99999, p = 0.0012). Glasgow coma scale (GCS) score on admission was also observed to be associated with poor prognoses (OR = 0.93, 95% CI = 0.89145-0.97290, p = 0.0029). Conclusions Low CSF cell count and low GCS on admission were observed as risk factors for poor prognoses in patients with bacterial meningitis.

Detection and Management of Elevated Intracranial Pressure in the Treatment of Acute Community-Acquired Bacterial Meningitis: A Systematic Review.

Acute bacterial meningitis (ABM) is associated with severe morbidity and mortality. The most prevalent pathogens in community-acquired ABM are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Other pathogens may affect specific patient groups, such as newborns, older patients, or immunocompromised patients. It is well established that ABM is associated with elevated intracranial pressure (ICP). However, the role of ICP monitoring and management in the treatment of ABM has been poorly described.An electronic search was performed in four electronic databases: PubMed, Web of Science, Embase, and the Cochrane Library. The search strategy chosen for this review used the following terms: Intracranial Pressure AND (management OR monitoring) AND bacterial meningitis. The search yielded a total of 403 studies, of which 18 were selected for inclusion. Eighteen studies were finally included in this review. Only one study was a randomized controlled trial. All studies employed invasive ICP monitoring techniques, whereas some also relied on assessment of ICP-based on clinical and/or radiological observations. The most commonly used invasive tools were external ventricular drains, which were used both to monitor and treat elevated ICP. Results from the included studies revealed a clear association between elevated ICP and mortality, and possibly improved outcomes when invasive ICP monitoring and management were used. Finally, the review highlights the absence of clear standardized protocols for the monitoring and management of ICP in patients with ABM. This review provides an insight into the role of invasive ICP monitoring and ICP-based management in the treatment of ABM. Despite weak evidence certainty, the present literature points toward enhanced patient outcomes in ABM with the use of treatment strategies aiming to normalize ICP using continuous invasive monitoring and cerebrospinal fluid diversion techniques. Continued research is needed to define when and how to employ these strategies to best improve outcomes in ABM.

Determinants of mortality among pediatric patients admitted to Wolaita Sodo University Comprehensive Specialized Hospital with acute bacterial meningitis, Southern Ethiopia: an unmatched case-control study.

BACKGROUND: People of all ages suffer from acute bacterial meningitis, but children are the most vulnerable, accounting for over 50% of all cases and deaths in children under the age of five. It is the leading cause of morbidity, mortality, and long-term suffering worldwide. Children are at great risk of disease and mortality due to a lack of specific immunity associated with their young age. As a result, determinants of death were found among pediatric patients treated with acute bacterial meningitis at Wolaita Sodo University Comprehensive Specialized Hospital in Southern Ethiopia. METHODS: A facility-based unmatched case-control study was conducted on pediatric patients admitted with acute bacterial meningitis at Wolaita Sodo University Comprehensive Specialized Hospital from July 1, 2019, to June 30, 2022. A total of 355 (71 cases and 284 controls) pediatric medical charts were used for data extraction using a preestablished checklist. Data were checked for completeness and consistency, entered into Epi-Data version 4.6 software, and transported to SPSS version 25 for analysis. Multivariable logistic regression analysis was performed to identify the independent determinants of acute bacterial meningitis mortality at a P value of < 0.05 along with a 95% confidence interval (CI). RESULTS: Age between 2 months and 5 years (adjusted odds ratio (AOR) = 3.19, 95% CI = 1.15-8.88), admission in the summer season (AOR = 0.27, 95% CI = 0.15-0.49), and family size greater than or equal to six (AOR = 3.13, 95% CI = 1.76-5.56), initial antibiotic change (AOR = 10.81, 95% CI = 2.10-55.7), clinical features at presentation such as loss of consciousness (AOR = 16.90, 95% CI = 4.70-60.4), abnormal body movements (seizures) (AOR = 6.51, 95% CI = 1.82-23.4), increased intracranial pressure (AOR = 3.63, 95% CI = 1.78-7.4), malnutrition (AOR = 2.98, 95% CI = 1.34-6.59) and presence of more than one comorbidity (AOR = 3.03, 95% CI = 1.03-9.03) were found to be determinants of acute bacterial meningitis mortality. CONCLUSIONS: In summary, children aged 2 months to 5 years from large families ( > = 6) with a history of initial antibiotic change, malnutrition, more than one comorbidity, and worse clinical characteristics were related to greater death due to acute bacterial mortality in this study.

Blood-brain barrier dysfunction in intensive care unit.

The central nervous system is characterized by a peculiar vascularization termed blood-brain barrier (BBB), which regulates the exchange of cells and molecules between the cerebral tissue and the whole body. BBB dysfunction is a life-threatening condition since its presence corresponds to a marker of severity in most diseases encountered in the intensive care unit (ICU). During critical illness, inflammatory response, cytokine release, and other phenomena activating the brain endothelium contribute to alterations in the BBB and increase its permeability to solutes, cells, nutrients, and xenobiotics. Moreover, patients in the ICU are often old, with underlying acute or chronic diseases, and overly medicated due to their critical condition; these factors could also contribute to the development of BBB dysfunction. An accurate diagnostic approach is critical for the identification of the mechanisms underlying BBB alterations, which should be rapidly managed by intensivists. Several methods were developed to investigate the BBB and assess its permeability. Nevertheless, in humans, exploration of the BBB requires the use of indirect methods. Imaging and biochemical methods can be used to study the abnormal passage of molecules through the BBB. In this review, we describe the structural and functional characteristics of the BBB, present tools and methods for probing this interface, and provide examples of the main diseases managed in the ICU that are related to BBB dysfunction.

German guidelines on community-acquired acute bacterial meningitis in adults.

INTRODUCTION: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis. RECOMMENDATIONS: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that -if the imaging findings do not indicate otherwise -a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases. CONCLUSIONS: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis.

Prevalence, aetiology, vaccination coverage and spatio-temporal pattern among patients admitted with acute bacterial meningitis to the sentinel hospital surveillance network in Yemen, 2014-20, before and during the civil war.

BACKGROUND: Acute bacterial meningitis (ABM) is a serious health issue in Yemen where civil war, which continues unabated, has crippled the healthcare system. We conducted a nationwide retrospective observational study in Yemeni sentinel hospitals to identify the prevalence, aetiology, vaccination coverage and spatio-temporal pattern of ABM in children aged <5 years before and during the civil war, 2014-20. METHODS: Cerebrospinal fluid samples were collected from hospitalized children and were analysed macroscopically for appearance and microscopically by Gram stain and white blood cell count. Culture and latex agglutination tests were performed. Data on the prevalence of and vaccination coverage for ABM were obtained from the Ministry of Health. Joinpoint regression was used to assess the annual percent change (APC) of ABM prevalence and vaccination coverage. Pearson's correlation was used to evaluate the association between ABM prevalence and vaccination coverage. RESULTS: In total, 11 339 hospitalized children had suspected cases of ABM (prevalence, 40.07/100 000 of the whole Yemeni population) and 2.6% (293/11 339) of suspected ABM cases were confirmed (prevalence, 1.04/100 000 of the whole Yemeni population). The dominant pathogens were Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). The civil war reduced the Hib and pneumococcal vaccination coverage (APC = -1.92), reaching its lowest (79.5%) in 2018. The prevalence of suspected ABM increased (APC = 3.46), reaching its maximum (6.08/100 000 of the whole Yemeni population) in 2019. The conflict inversely correlated with the ABM prevalence and vaccination coverage (Pearson correlation coefficient (r), -0.69 to -0.53). Ta'izz region, which was severely affected by the civil war, had the highest prevalence of suspected ABM (120.90/100 000 of the whole Yemeni population) and lowest vaccination coverage (60%). CONCLUSIONS: The civil war had a negative impact on vaccination coverage and coincided with increasing prevalence of ABM in Yemen. Streptococcus pneumoniae is the dominant causative pathogen.

Daptomycin for the treatment of acute bacterial meningitis: A narrative review.

BACKGROUND: There is growing interest in the utilization of daptomycin for the treatment of multi-drug-resistant, Gram-positive infections. Pharmacokinetic studies suggest that daptomycin could penetrate into the cerebrospinal fluid, albeit to a small extent. The objective of this review was to evaluate the available clinical evidence for the use of daptomycin in acute bacterial meningitis of both paediatric and adult patients. METHODS: Electronic databases were searched up to June 2022 for studies published on the topic. The inclusion criteria were met if the study reported the use of intravenous daptomycin (more than a single dose) for the treatment of diagnosed acute bacterial meningitis. RESULTS: In total, 21 case reports were identified that met the inclusion criteria. These suggest that daptomycin could be a safe and effective alternative to achieve clinical cure of meningitis. In these studies, daptomycin was used in the event of treatment failure, patient intolerance or bacterial resistance to first-line agents. CONCLUSIONS: Daptomycin has potential to be an alternative to standard care for meningitis caused by Gram-positive bacteria in the future. However, more robust research is required to establish an optimal dosing regimen, duration of therapy, and place in therapy for the management of meningitis.

Pseudo Subarachnoid Hemorrhage Sign in Bacterial Meningitis in a Patient Presenting With Acute Ischemic Stroke: A Novel Radiological Clue to Rapid Diagnosis.

Pseudo subarachnoid hemorrhage (SAH) is an entity defined when characteristic computed tomography (CT) findings of SAH are seen without evidence of hemorrhage on MRI, autopsy, or cerebrospinal fluid analysis. This imaging phenomenon has been reported in association with multiple clinical settings including diffuse cerebral edema, hypoxic-ischemic injury, post percutaneous coronary intervention, and the focus of our report, acute bacterial meningitis. The mechanisms leading to this finding are poorly understood. Current hypotheses explaining this pattern vary widely depending on the associated pathology. In this report, we present a case of pseudo SAH associated with bacterial meningitis and a literature review on the causes, neuroimaging findings, and mechanisms associated with pseudo SAH. We discuss dual energy CT as a possible tool for differentiating pseudo SAH from true SAH. We analyze the timing of imaging studies and the role timing plays in the presentation of the pseudo SAH sign. We conclude that the extravasation of iodine contrast into the subarachnoid space can mimic SAH on CT. Ultimately, our case adds to the growing body of evidence that clinicians should be aware of acute bacterial meningitis as a potential mimic of SAH on CT.

Clinical use of multiplex-PCR for the diagnosis of acute bacterial meningitis.

Background and Objectives: Prompt and accurate diagnosis of acute bacterial meningitis (ABM) is critical for patient management. We designed and evaluated two sets of multiplex-PCR assays for the simultaneous detection of six major etiologies of ABM i.e., Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis in one set and Listeria monocytogenes, Streptococcus agalactiae, and Escherichia coli in another set of multiplex-PCR in CSF of patients with suspected ABM. Methods: A total of 113 CSF specimens from patients of all ages having clinical features suggestive of meningitis were tested for bacteriological evidence by Gram's smear, culture, and our designed multiplex-PCR. Results: Multiplex-PCR assay performed excellently by increasing the overall detection rate by 6% when compared to culture as of total 113 samples tested, 17 (15%) were positive by multiplex-PCR whereas only 9% (10/113) were positive by culture. It detected the DNA in eight culture negative samples revealing the presence of S. pneumoniae in three and other possible bacterial pathogens in five of them. Our assay showed a DNA detection limit of 1 pg/µL. Compared to CSF culture, the sensitivity and specificity of the multiplex-PCR were 90% and 92.2%, respectively. Conclusion: This study accentuates the importance of multiplex-PCR assay that is efficiently fast and reliable for the diagnosis of acute bacterial meningitis that can substantially improve the diagnosis in culture negative cases, especially in patients who were previously started on antimicrobial therapy.

Defeating meningitis by 2030 - an ambitious target.

Acute bacterial meningitis remains a major cause of mortality and morbidity, especially in lower-income countries. Thus, in 2017, a group of people concerned with this continuing problem came together to plan a way forward. A task force was established, a baseline situation analysis undertaken and a road map for a new initiative 'Defeating Meningitis by 2030' prepared. This road map will be launched officially in September 2021. Additional finances for meningitis control will be needed, together with the support of many different institutions and people with different skills, if the 'Defeating Meningitis by 2030' initiative is to achieve its ambitious goals.

A cross-sectional study of etiological and sensitivity profiling of meningitis in under-five children.

Objectives: The study aimed to understand the organism spectrum and antibiotic sensitivity profile of acute bacterial meningitis in pediatric population. Methods: A cross-sectional study was conducted at the department of microbiology of a tertiary care center for a period of 18 months. Suspected cases of meningitis between 1 and 60 months of age were considered for the study. All cases underwent cerebrospinal fluid tap for direct microscopy (DM), Gram staining, and culture sensitivity. Results: The mean age of the study patients was 10.42 months, with 61.7% of males and 38.3% of females. DM and culture were positive in 22.90% and 28.00% of the patients, respectively. On Gram stain, there were 29 (59.18%) cases of Gram positivity and 20 (40.82%) cases of Gram negativity. The culture growth showed that Acinetobacter spp. was isolated in 15 (30.6%) of the cases. Enterococcus spp. was isolated in 9 (18.4%) of the cases. Klebsiella pneumoniae was isolated in 8 (16.3%) of the cases. Staphylococcus aureus was isolated in 8 (16.3%) of the cases. Enterobacter spp. was isolated in 3 (6.12%) of the cases. Pseudomonas aeruginosa was isolated in 3 (6.12%) of the cases. Streptococcus pneumoniae was isolated in 3 (6.1%) of the cases. The antibiogram of different agents showed wide variation, with colistin being 100% sensitive for Acinetobacter, Enterobacter, K. pneumoniae, and P. aeruginosa. Conclusion: The present study revealed that Acinetobacter, Enterococcus, K. pneumoniae, and S. aureus were the most common bacterial etiologic agents of ABM. The 100% antibiotic sensitivity of the organisms to some antibiotics may suggest the use of such antibiotics while awaiting for culture sensitivity reports.

Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies.

Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.

Developing a Prognostic Model to Predict Mortality in Patients with Acute Bacterial Meningitis.

Bacterial meningitis is one of the harmful and deadly infectious diseases, and any delay in its treatment will lead to death. In this paper, a prognostic model was developed to predict the risk of death amongst probable cases of bacterial meningitis. Our prognostic model was developed using a decision tree algorithm on the national meningitis registry of the Iranian Center for Disease and Prevention (ICDCP) containing 3,923 records of meningitis suspected cases in 2018-2019. The most important features have been selected for the model construction. This model can predict the mortality risk for the meningitis probable cases with 78% accuracy, 84% sensitivity, and 73% specificity. The identified variables in prognosis the death included age and CSF protein level. CSF protein level (mg/dl) <= 65 versus > 65 provided the first branch of our decision tree. The highest mortality risk (85.8%) was seen in the patients >65 CSF protein level with 30 years < of age. For the patients <=30 year of age with CSF protein level >137 (mg/dl), the mortality risk was 60%. The prognostic factors identified in the present study draw the attention of clinicians to provide early specific measures, such as the admission of patients with a higher risk of death to intensive care units (ICU). It could also provide a helpful risk score tool in decision-making in the early phases of admission in pandemics, decrease mortality rate and improve public health operations efficiently in infectious diseases.

Accuracy of Meningitis Bacterial Score (MBS) as an indicator in establishing the diagnosis of acute bacterial meningitis in adults.

Bacterial meningitis persists as a worldwide threat contributing to high mortality and morbidity rate, where differentiating bacterial meningitis from aseptic meningitis is key for better management and outcomes. Hence, this study aimed to assess the Bacterial Meningeal Score (BMS) as a tool for early diagnosis of acute bacterial meningitis. This study employed a retrospective cross-sectional method using medical records of patients with meningitis and meningoencephalitis who were hospitalized at Dr. Soetomo Hospital, from January 2018 to September 2021. Data of demographics, clinical, laboratory and cerebrospinal fluid (CSF) profile and culture were collected. The diagnostic performance of the BMS in diagnosing acute bacterial meningitis was evaluated by its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR +) and negative likelihood ratio (LR -). A total of 128 patients who had been diagnosed with meningitis and meningoencephalitis were included. Out of total patients, 53 samples were diagnosed with acute bacterial meningitis as confirmed by CSF culture. The sensitivity and specificity of BMS with cutoff >2.5 in diagnosing acute bacterial meningitis were 92.4% and 92.0%, respectively with PPV 89.1% and NPV 94.5%. The area under the curve (AUC) of BMS in diagnosing of acute bacterial meningitis was 95.6% (95%CI: 92.3%, 99%). A BMS score of greater than 2.5 indicates a high likelihood of acute bacterial meningitis, whereas a score less than 2.5 indicates a low likelihood.

Treatment Outcomes and Associated Factors among Children Hospitalized with Acute Bacterial Meningitis in Eastern Ethiopia: A Cross-Sectional Study.

BACKGROUND: Bacterial meningitis is a common central nervous system infection that is associated with high morbidity and mortality in pediatrics. In Ethiopia, little is known about treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children. OBJECTIVE: To assess treatment outcomes of acute bacterial meningitis and associated factors among hospitalized children with acute bacterial meningitis in the Hiwot Fana Specialized University Hospital pediatric ward. METHODS: A retrospective cross-sectional study was conducted at the pediatric ward of Hiwot Fana Specialized University Hospital, eastern Ethiopia. Relevant data were collected using a structured data-collection tool from patients' medical charts. Bivariate and multivariate logistic regression analyses were done to identify predictors of treatment outcomes. OR with 95% CI and P≤0.05 was used for statistical significance. RESULTS: A total of 200 children with acute bacterial meningitis were included in the study, of which 92% were aged ≥2 months and the majority (128, 64%) had delayed (≥72 hours) presentation to the hospital. At admission, 181 (90.5%) were febrile, 92 (46%) had depressed level of consciousness, and 40 (20%) had had seizures. Most (126, 63%) had documented medical comorbidities. The antibiotic combination of ampicillin and gentamycin had been frequently administered in children aged <2 months while ceftriaxone was commonly prescribed for those aged >2 months. Of the total study participants, 154 (77%) showed successful treatment outcomes, while 46 (23%) experienced poor treatment outcomes (died or "self"-discharged). Level of consciousness (AOR 3.25, 95% CI 1.21-8.75), duration of illness before admission (AOR 3.74, 95% CI 1.76-7.98), and antibiotic-regimen change (AOR 4.7, 95% CI 2.4-10) were predictors of treatment outcomes. CONCLUSION: The majority of study participants experienced good treatment outcomes. Unconsciousness, antibiotic-regimen change, and duration of illness before hospitalization were significantly associated with treatment outcomes. Early treatment, linkage of primary-health facilities to tertiary health-care centers, and availability of diagnostics should be promoted to improve patient outcomes.

A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae. METHODS: We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection. RESULTS: Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all). CONCLUSIONS: The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.

Impact of 10-Valent Pneumococcal Conjugate Vaccine on Bacterial Meningitis in Madagascar.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Madagascar in 2012. The objective of this study was to determine the impact of PCV10 on bacterial meningitis in hospitalized children <5 years of age. METHODS: During 2010-2017, data from the hospital admission logbook were recorded for bacterial meningitis and pneumonia hospitalizations in children <5 years of age. Between April 2011 and December 2017, 3312 cerebrospinal fluid (CSF) samples collected from children who fulfilled the World Health Organization case definition of suspected bacterial meningitis were analyzed at the sentinel site laboratory (SSL) by microscopy, culture, and antigen detection tests. A total of 2065 CSF samples were referred to the regional reference laboratory for real-time polymerase chain reaction (RT-PCR) analysis. 2010-2011 was defined as the prevaccine period, 2012 as vaccine introduction year, and 2013-2017 the postvaccine period. The number of cases, causative agent, and pneumonia hospitalizations were compared before and after PCV10 introduction. RESULTS: In the prevaccine period, bacterial meningitis and pneumonia hospitalizations accounted for 4.5% and 24.5% of all hospitalizations while there were 2.6% and 19%, respectively, in the postvaccine period (P < .001). In samples tested at the SSL, 154 were positive with 80% Streptococcus pneumoniae and 20% other bacteria. Pneumococcal meningitis diagnosed by RT-PCR declined from 14% in 2012 to 3% in 2017. Also, 14% of children with pneumococcal meningitis died. CONCLUSIONS: Following PCV10 introduction, pneumococcal meningitis, bacterial meningitis, and pneumonia hospitalizations declined. Surveillance should continue to monitor the impact of PCV10.

Rapid diagnosis of bacterial meningitis by nanopore 16S amplicon sequencing: A pilot study.

Early administration of antibiotics is crucial in the management of bacterial meningitis. Rapid pathogen identification helps to make a definite diagnosis of bacterial meningitis and enables tailored antibiotic treatment. We investigated if the 16S amplicon sequencing performed by MinION, a nanopore sequencer, was capable of rapid pathogen identification in bacterial meningitis. Six retrospective cases of confirmed bacterial meningitis and two prospective cases were included. The initial cerebrospinal fluid (CSF) samples of these patients were used for the experiments. DNA was extracted from the CSF, and PCR was performed on the 16S ribosomal DNA (16S rDNA). Sequencing libraries were prepared using the PCR products, and MinION sequencing was performed for up to 3 h. The reads were aligned to the bacterial database, and the results were compared to the conventional culture studies. Pathogenic bacteria were successfully detected from the CSF by 16S sequencing in all retrospective cases. 16S amplicon sequencing was more sensitive than conventional diagnostic tests and worked properly even in antibiotics-treated samples. MinION sequencing significantly reduced the turnaround time, and even 10 min of sequencing was sufficient for pathogen detection in certain cases. Protocol adjustment could further increase the sensitivity and reduce the turnaround time for MinION sequencing. Finally, the prospective application of MinION 16S sequencing was successful. Nanopore 16S amplicon sequencing is capable of rapid bacterial identification from the CSF of the bacterial meningitis patients. It may have many advantages over conventional diagnostic tests and should therefore be applied in a larger number of patients in the future.

Austrian Syndrome - A Devastating Osler's Triad: Case Report and Literature Review.

Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by Streptococcus pneumoniae. We present a case of the Austrian syndrome in the oldest patient in the reviewed literature, with no other classically described risk factors. She had an unusual initial presentation and microorganism portal of entry. Her hospital course was complicated by the diagnosis of monoclonal gammopathy, septic knee joint, septic brain emboli and respiratory failure. We also provide an extensive review of available literature of this commonly unrecognized entity.

[Etiology, Prognosis and Risk Factors of 181 Adult Community-acquired Acute Bacterial Meningitis].

OBJECTIVE: To understand the etiology, clinical prognosis and risk factors of adult community-acquired acute bacterial meningitis (ABM) and provide the evidence for clinical diagnosis and treatment. METHODS: We performed a retrospective study of 181 clinically diagnosed hospitalized patients with community-acquired adult ABM from Jan.2010 to Jan.2018. The patients were categorized as non-elderly (16≤age<65 years old, n=156 ) and elderly (age≥65 years old, n=25) group. The etiology, clinical features, prognosis and risk factors of the two groups were compared. RESULTS: Sixty-four of 181 patients (35.4%) had pathogens detected. The most common pathogens were Streptococcus pneumoniae (17.9%), Listeria monocytogenes (13.4%) and Klebsiella pneumoniae (10.5%). The mortality of the elderly group was higher than that of the non-elderly group (P<0.05). Univariate analysis showed that there was a significant difference between the elderly group and the non-elderly group in the incidence of hypertension, hypokalemia, pulmonary infection, ear-nose-throat ( ENT) infection, cerebrospinal fluid (CSF) protein concentration, head CT abnormalities and mortality. Logistic regression analysis showed that pulmonary infection and temperature ≥38.5 ℃ were independent risk factors for poor prognosis in the non-elderly group. CSF pressure ≥200 mmH2O was a independent risk factors for poor prognosis in the elderly group. CONCLUSION: The pathogens that cause acute bacterial meningitis in adult community are mainly Streptococcus pneumoniae, Listeria monocytogenes and Klebsiella pneumoniae.Pulmonary infection and temperature ≥38.5 ℃ are independent risk factors of poor prognosis in the non-elderly patients, as CSF pressure ≥200 mmH2O a independent risk factor in the elderly patients.