Community-acquired Meningitis Research Articles

Recurrent community-acquired pneumococcal meningitis in adults with and without identified predisposing factors.

Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.

Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study

ObjectivesThe objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. MethodsWe quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). ResultsBacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51–68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103–1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9–105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0–2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6–2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4–3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6–3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6–3.9; p < 0.001). DiscussionHigh CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.

Epidemiology, clinical profile, and outcomes of CSF-diversion catheter-related infections – Prospective cohort study results from a single quaternary neurosurgery referral centre

BackgroundDevice-associated CNS infections is a major subgroup of healthcare associated CNS infections. Healthcare-associated ventriculitis or meningitis differs considerably from community-acquired meningitis in its epidemiology, pathogenesis, clinical presentation and management. ObjectivesThis study aimed to identify the infection rates, the associated risk factors, and outcomes of these life-threatening infections. MethodsThis was a 2-year single center prospective cohort study. Patient's clinical data, laboratory parameters, treatment and their outcomes were collected using data collection tool, and device days were collected from the hospital information system (HIS). Patients were categorised using IDSA criteria as contamination or colonisation or infection. Cox regression model was used for multivariate analysis to estimate hazard risk. ResultsA total of 578 CSF diversion catheters were inserted in 472 patients. The average rate for EVD and LD infection were 11.12 and 11.86 per 1000 device days respectively. The average infection rates for VP and LP shunts were 6% and 5.2% per procedure, respectively. The commonest etiological agent causing CSF diversion catheter-related infection (CDRI) was Klebsiella pneumoniae (n = 14, 40%). The risk factors which were independently associated with increased infection risk by cox regression analysis were drain insertion ≥7 days [HR:11.73, p −0.03], posterior approach of EVD insertion (occipital) [HR:9.53, p - 0.01], pre-OP ASA score>3 [HR:8.28, p - 0.013] presence of EVD/LD leak [HR: 17.24, p < 0.0001], male gender [HR:2.05, p-0.05] and presence of associated peri-operative scalp infections [HR:3.531, p-0.005]. Shift to narrow spectrum surgical prophylactic antibiotic [Coefficient: −1.284, p-0.03] and reduction in CSF sampling frequency [Coefficient: −1.741, p-0.02] were found to be negatively associated with CDRI. ConclusionsThe study demonstrated drain insertion ≥7 days, posterior approach of EVD insertion, presence of EVD/LD leak, male gender and presence of associated peri-operative scalp skin and soft tissue infections were associated with increased risk of infection.

The application value of metagenomic next-generation sequencing in community-acquired purulent meningitis after antibiotic intervention

BackgroundBacteria account for nearly one third of the causes of community-acquired central nervous system infections, and traditional diagnostic methods are based on culture results, which are time-consuming and have a low detection rate leading to delayed diagnosis and treatment. Since metagenomic next-generation sequencing (mNGS) has the advantages of high timeliness and only detecting microbial trace gene fragments, it has been used more widely in recent years. Based on this, we explored whether the application of cerebrospinal fluid (CSF) mNGS is advantageous in patients with community-acquired purulent meningitis, especially in people who have already used antibiotics.MethodsThis was a retrospective study of 63 patients with community-acquired purulent meningitis admitted to the Department of Neurology of Shanxi Bethune Hospital from March 2018 to November 2022. Data were systematically collected and classified into CSF culture group, blood culture group and CSF mNGS group according to different detection methods, and the total detection rate of each method was calculated. Each group of patients was divided into two subgroups according to whether antibiotics were used before sampling. The detection rates of the three groups were compared within and between groups to explore whether mNGS has advantages over traditional methods and the influence of antibiotic use on detection rates of the three methods.ResultsAmong the 63 patients, the cases of CSF culture, blood culture and CSF mNGS were 56, 46, 44, respectively. The total detection rates of the three methods were 17.86%, 36.96%, 81.82%, with statistical differences (p < 0.05),suggesting that the detection rate of mNGS was higher than CSF culture (p < 0.05) and blood culture (p < 0.05),and the detection rate of blood culture higher than CSF culture (p < 0.05). Further grouping found that without antibiotics, the detection rates of CSF culture, blood culture and CSF mNGS were 28.57%, 56.25% and 88.89%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was higher than that of CSF culture (p < 0.05), but there was no statistical difference between CSF and blood culture (p > 0.05), nor between blood culture and CSF mNGS (p > 0.05). The detection rates of the three groups with antibiotics were 14.29%, 26.67% and 80.00%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was still higher than CSF culture (p < 0.05) and blood culture (p < 0.05). However, the detection rate of CSF mNGS also decreased after antibiotics were used for more than 3 days.ConclusionsThe detection rate of CSF mNGS in patients with purulent meningitis is higher than traditional methods, especially in patients who have been given antibiotics, but the detection rate will decrease with the extension of antibiotic use.

Elizabethkingia meningoseptica: Changing anti microbial resistance causing fatal community-acquired neonatal meningitis – An area of rising concern

Elizabethkingia meningoseptica is often reported as a hospital-acquired infection. We present an unusual fatal case of community-acquired meningitis probably secondary to contamination of the breast pump and feeding bottle used at home. Despite being a Gram-negative bacillus, it is extremely sensitive to antibiotics used to treat Gram-positive infections. There is a lack of protocolized effective treatment regimens and the organism demonstrates in vitro resistance to many antibiotics but a changing pattern of resistance as seen in our case is not reported till date. E. meningoseptica is an emerging potential source of neonatal infection and is an upcoming public health problem.

Evaluation of the QIAstat-Dx Meningitis/Encephalitis Panel, a multiplex PCR platform for the detection of community-acquired meningoencephalitis.

Rapid identification of the causative pathogens of central nervous system infections is essential for providing appropriate management and improving patient outcomes. The performance of QIAstat-Dx Meningitis/Encephalitis (ME) Panel-a multiplex PCR testing platform-in detecting pathogens implicated in meningitis and/or encephalitis was evaluated using BioFire FilmArray ME Panel as a comparator method. This multicenter study analyzed 585 retrospective residual cerebrospinal fluid specimens and 367 contrived specimens. The QIAstat-Dx ME Panel showed positive percent agreement (PPA) values of 100% for Neisseria meningitidis, Streptococcus agalactiae, Escherichia coli K1, Listeria monocytogenes, and Cryptococcus gattii/neoformans on clinical samples compared to the BioFire FilmArray ME Panel. The PPA values observed for Haemophilus influenzae and Streptococcus pneumoniae were 80% and 88.24%, respectively. Negative percent agreement (NPA) values were >99.0% for each of the six bacterial targets and one fungal target tested with clinical samples. One viral target, herpes simplex virus 1, exhibited a PPA value of 100.0%, while the remaining viral targets-human parechovirus, herpes simplex virus 2, human herpes virus 6, and varicella zoster virus-were >90.0%, with the exception of enterovirus, which had a PPA value of 77.8%. The QIAstat-Dx ME Panel detected five true-positive and four true-negative cases compared to BioFire FilmArray ME Panel. The NPA values for all viral pathogens were >99.0%. Overall, the QIAstat-Dx ME Panel showed comparable performance to the BioFire FilmArray ME Panel as a rapid diagnostic tool for community-acquired meningitis and encephalitis.

The choline-binding proteins PspA, PspC, and LytA of Streptococcus pneumoniae and their interaction with human endothelial and red blood cells.

Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of S. pneumoniae. In vitro biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of S. pneumoniae on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of S. pneumoniae. Hence, in addition to their structural function within the cell wall of S. pneumoniae, each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis.

Penicillin-binding protein genotyping of penicillin-nonsusceptible Streptococcus pneumoniae isolates from the nasopharynx of healthy preschool children

Abstract Streptococcus pneumoniae is one of the most frequent bacterial identified causes of community-acquired pneumonia, otitis media and meningitis. It is, as well, a common cause of bacteraemia’s significant morbidity and mortality. Beta-lactam antibiotics (BLAs) are the first line of empirical treatment for pneumococcal infections. The targets of BLAs are penicillin-binding proteins (PBPs), the modifications of which are one of the reasons why pneumococci are non-susceptible to BLAs. In our work, a total of 39 Streptococcus pneumoniae isolates were obtained from 176 healthy children, both vaccinated and non-vaccinated. The isolates were tested for antimicrobial susceptibility, and their penicillin-binding proteins (PBPs) were typed by the restriction fragment length of the polymorphism analysis of their pbp genes. The most frequent serotypes among the penicillin non-susceptible Streptococcus pneumoniae (PNSSP) isolates were 23B, 35B and 19F. Restriction enzyme analyses of pbp1a, pbp2b, and pbp2x genes revealed 5, 3 and 3 different patterns, respectively, and a total of 4 different PBPs profiles of PNSSP isolates belonging to serotypes not included in pneumococcal conjugate vaccines were demonstrated. We conclude that the level of resistance should be monitored constantly to ascertain the effect of current pneumococcal conjugate vaccines, as well as to recognize new circumstances developing in Poland, as well as the possibility of multiple, independent imports of resistant strains from abroad.

Molecular mechanism of Streptococcus pneumoniae-targeting xenophagy recognition and evasion: Reinterpretation of pneumococci as intracellular bacteria.

Streptococcus pneumoniae is a major, encapsulated Gram-positive pathogen that causes diseases including community-acquired pneumonia, meningitis, and sepsis. This pathogen colonizes the nasopharyngeal epithelia asymptomatically but can often migrate to sterile tissues and cause life-threatening invasive infections (invasive pneumococcal disease). Although multivalent pneumococcal polysaccharides and conjugate vaccines are available and effective, they also have major shortcomings with respect to the emergence of vaccine-resistant serotypes. Therefore, alternative therapeutic approaches are needed, and the molecular analysis of host-pathogen interactions and their applications to pharmaceutical development and clinical practice has recently received increased attention. In this review, we introduce pneumococcal surface virulence factors involved in pathogenicity and highlight recent advances in our understanding of host autophagy recognition mechanisms against intracellular S. pneumoniae and pneumococcal evasion from autophagy.

Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease.

Anaerobic bacteria are responsible for half of all pulmonary infections. One such pathogen is Streptococcus pneumoniae (Spn), a leading cause of community-acquired pneumonia, bacteremia/sepsis, and meningitis. Using a panel of isogenic mutants deficient in lactate, acetyl-CoA, and ethanol fermentation, as well as pharmacological inhibition, we observed that NAD(H) redox balance during fermentation was vital for Spn energy generation, capsule production, and in vivo fitness. Redox balance disruption in fermentation pathway-specific fashion substantially enhanced susceptibility to killing in antimicrobial class-specific manner. Blocking of alcohol dehydrogenase activity with 4-methylpyrazole (fomepizole), an FDA-approved drug used as an antidote for toxic alcohol ingestion, enhanced susceptibility of multidrug-resistant Spn to erythromycin and reduced bacterial burden in the lungs of mice with pneumonia and prevented the development of invasive disease. Our results indicate fermentation enzymes are de novo targets for antibiotic development and a novel strategy to combat multidrug-resistant pathogens.

Dynamics of community-acquired meningitis syndrome outbreaks in southern France.

In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher's exact test (p < 10-3). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases (p < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1-2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks.

Real-time metagenomics-based diagnosis of community-acquired meningitis: A prospective series, southern France.

SummaryBackgroundPoint-Of-Care (POC) diagnosis of life-threatening community-acquired meningitis currently relies on multiplexed RT-PCR assays, that lack genotyping and antibiotic susceptibility profiling. We assessed the usefulness of real-time metagenomics (RTM) directly applied to the cerebrospinal fluid (CSF) for the identification, typing and susceptibility profiling of pathogens responsible for community-acquired meningitis.MethodsA series of 52 CSF samples from patients suspected of having community-acquired meningitis, were investigated at POC by direct RTM in parallel to routine real-time multiplex PCR (RT-PCR) and bacterial culture, for the detection of pathogens. RTM-generated sequences were blasted in real-time against an in-house database incorporating the panel of 12 most prevalent pathogens and against NCBI using EPI2ME online software, for pathogen identification. In-silico antibiogram and genotype prediction were determined using the ResFinder bio-tool and MLST online software.FindingsOver eight months, routine multiplex RT-PCR yielded 49/52 positive CSFs, including 21 Streptococcus pneumoniae, nine Neisseria meningitidis, eight Haemophilus influenzae, three Streptococcus agalactiae, three Herpesvirus-1, two Listeria monocytogenes, and one each of Escherichia coli, Staphylococcus aureus and Varicella-Zoster Virus. Parallel RTM agreed with the results of 47/52 CSFs and revealed two discordant multiplex RT-PCR false positives, one H. influenzae and one S. pneumoniae. Both multiplex RT-PCR and RTM agreed on the negativity of three CSFs. While multiplex RT-PCR routinely took 90 min, RTM took 120 min, although the pipeline analysis detected the pathogen genome after 20 min of sequencing in 33 CSF samples; and after two hours in 14 additional CSFs; yielding > 50% genome coverage in 19 CSFs. RTM identified 14 pathogen genotypes, including a majority of H. influenzae b, N. meningitidis B and S. pneumoniae 11A and 3A. In all 16 susceptible cultured bacteria, the in-silico antibiogram agreed with the in-vitro antibiogram in 10 cases, available within 48 h in routine bacteriology.InterpretationIn addition to pathogen detection, RTM applied to CSF samples offered supplementary information on bacterial profiling and genotyping. These data provide the proof-of-concept that RTM could be implemented in a POC laboratory for one-shot diagnostic and genomic surveillance of pathogens responsible for life-threatening meningitis.FundingThis work was supported by the French Government under the Investments in the Future programme managed by the National Agency for Research reference: Méditerranée Infection 10-IAHU-03.

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide vaccines, conjugate vaccines have shown consistent efficacy against nasopharyngeal carriage and noninvasive pneumonia overall and for some prevalent individual serotypes. Given these different clinical profiles, it is crucial to understand the differential immunological responses induced by these two vaccines. Here, we used a high-throughput systems serology approach to profile the biophysical and functional features of serum antibodies induced by PCV13 and PPSV23 at 1 month and 1 year. In comparison with PPSV23, PCV13 induced higher titers across antibody isotypes; more durable antibody responses across immunoglobulin G (IgG), IgA, and IgM isotypes; and increased antigenic breadth. Although titers measured in opsonophagocytic activity (OPA) assays were similar between the two groups, confirming what was observed in clinical studies, serum samples from PCV13 vaccinees could induce additional non-OPA antibody-dependent functions, including monocyte phagocytosis and natural killer cell activation. In a multivariate modeling approach, distinct humoral profiles were demonstrated in each arm. Together, these results demonstrate that the glycoconjugate PCV13 vaccine induces an antigenically broader, more durable, polyfunctional antibody response. These findings may help explain the increased protection against S. pneumoniae colonization and noninvasive pneumonia and the longer duration of protection against invasive pneumococcal disease, mediated by PCV13.

Cryptococcus neoformans Genotypic Diversity and Disease Outcome among HIV Patients in Africa.

Cryptococcal meningoencephalitis, a disease with poor patient outcomes, remains the most prevalent invasive fungal infection worldwide, accounting for approximately 180,000 deaths each year. In several areas of sub-Saharan Africa with the highest HIV prevalence, cryptococcal meningitis is the leading cause of community-acquired meningitis, with a high mortality among HIV-infected individuals. Recent studies show that patient disease outcomes are impacted by the genetics of the infecting isolate. Yet, there is still limited knowledge of how these genotypic variations contribute to clinical disease outcome. Further, it is unclear how the genetic heterogeneity of C. neoformans and the extensive phenotypic variation observed between and within isolates affects infection and disease. In this review, we discuss current knowledge of how various genotypes impact disease progression and patient outcome in HIV-positive populations in sub-Saharan African, a setting with a high burden of cryptococcosis.

Direct Metagenomic Diagnosis of Community-Acquired Meningitis: State of the Art.

Current routine diagnosis of community-acquired meningitis (CAM) by multiplex real-time polymerase chain reaction (RT-PCR) is limited in the number of tested pathogens and their full characterisation, requiring additional in vitro investigations to disclose genotype and antimicrobial susceptibility. We reviewed 51 studies published through December 2021 reporting metagenomic next generation sequencing (mNGS) directly applied to the cerebrospinal fluid (CSF). This approach, potentially circumventing the above-mentioned limitations, indicated 1,248 investigated patients, and 617 patients dually investigated by routine diagnosis and mNGS, in whom 116 microbes were detected, including 50 by mNGS only, nine by routine methods only, and 57 by both routine methods and mNGS. Of 217 discordant CSF findings, 103 CSF samples were documented by mNGS only, 87 CSF samples by routine methods only, and 27 CSF samples in which the pathogen identified by mNGS was different than that found using routine methods. Overall, mNGS allowed for diagnosis and genomic surveillance of CAM causative pathogens in real-time, with a cost which is competitive with current routine multiplex RT-PCR. mNGS could be implemented at point-of-care (POC) laboratories as a part of routine investigations to improve the diagnosis and molecular epidemiology of CAM, particularly in the event of failure of routine assays.

Clinical management of community-acquired meningitis in adults in the UK and Ireland in 2017: a retrospective cohort study on behalf of the National Infection Trainees Collaborative for Audit and Research (NITCAR)

ObjectivesTo assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.DesignRetrospective cohort study.Setting64 UK and Irish hospitals.Participants1471 adults with community-acquired meningitis of any...

Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2)

IntroductionDespite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically...

Combined Bacterial Meningitis and Infective Endocarditis: When Should We Search for the Other When Either One is Diagnosed?

IntroductionWe aimed to describe patients with coexisting infective endocarditis (IE) and bacterial meningitis (BM).MethodsWe merged two large prospective cohorts, an IE cohort and a BM cohort, with only cases of definite IE and community-acquired meningitis. We compared patients who had IE and BM concurrently to patients with IE only and BM only.ResultsAmong the 1030 included patients, we identified 42 patients with IE–BM (4.1%). Baseline characteristics of patients with IE–BM were mostly similar to those of patients with IE, but meningitis was the predominant presentation at admission (39/42, 92.3%). Causative pathogens were predominantly Streptococcus pneumoniae (18/42, 42.9%) and Staphylococcus aureus (14/42, 33.3%). All pneumococcal IE were associated with BM (18/18). BM due to oral and group D streptococci, Streptococcus agalactiae, and S. aureus were frequently associated with IE (14/30, 46.7%). Three-month mortality was 28.6% in patients with IE–BM, 20.5% in patients with IE, and 16.6% in patients with BM.ConclusionsPatients with pneumococcal IE or altered mental status during IE must be investigated for BM. Patients with S. aureus, oral and group D streptococcal or enterococcal BM, or unfavorable outcome in pneumococcal meningitis would benefit from an echocardiography. Patients with the dual infection have the worst prognosis. Their identification is mandatory to initiate appropriate treatment.

Equal adhesion to pneumocytes by pneumococci inducing bacteraemia and pneumonia.

Streptococcus pneumoniae (S. pneumoniae) is a leading agent worldwide, which could cause community-acquired pneumonia, bacteraemia, and meningitis. However, the pathogeneses remain unclear. This study was conducted to investigate gene pneumococcal surface antigen A (psaA) expression and the adhesion differences of various S. pneumoniae strains. A total of 24 (N) S. pneumoniae strains were collected: 11 from blood (bd-SP), 12 from sputum (sd-SP) and one was ATCC49619. One millilitre of A549 pneumocytes (3.3×108/L) and 100 µl of each S. pneumoniae strain at 1.0 McFarland were mixed and incubated under 37oC and 5% CO2 for three hours. The cells were centrifuged and extracted for psaA mRNA analysis. The former experiment was redone. After culture, the adherent cells were collected and cultured on blood agar plates. The △CT values of psaA were 18.9, 29.9±2.5, 29.6±2.0 and 16.0, 17.0±3.3, 18.6±3.8 for ATCC49619, bd-SP and sd-SP before and after stimulation respectively, with the colony units of 23, 68.4±6.7 and 59.1±7.7, which showed equal adhesion between bd-SP and sd-SP. Moderate psaA expression and adhesion of S. pneumoniae might facilitate its pathogenesis, excess of which induces faster S. pneumoniae clearance.

Acute Bacterial Meningitis

Acute bacterial meningitis is a life-threatening infection. By definition, meningitis is an infection of the meninges and the subarachnoid space. Bacterial meningitis is associated with an inflammatory response that involves the meninges, the subarachnoid space, the brain parenchyma, and the cerebral arteries and veins. As such, bacterial meningoencephalitis is the more accurate descriptive term. This chapter discusses the epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, complications, and prognosis of the disease. The discussion of diagnosis covers clinical manifestations, physical examination findings, laboratory tests, and imaging studies. The discussion of treatment covers empirical therapy, specific antimicrobial therapy, and dexamethasone therapy. Graphs compare causative organisms and clinical manifestations of community-acquired meningitis. Illustrations depict proper patient positioning for detecting nuchal rigidity, Kernig sign, Brudzinski sign, and lumbar puncture, as well as a sagittal view of a lumbar puncture needle as it is advanced into the subarachnoid space. An algorithm delineates the approach to the patient with symptoms and signs of bacterial meningitis. Tables outline bacterial pathogens based on predisposing and associated conditions, cerebrospinal fluid diagnostic studies for meningitis, the appearance of the organism on a Gram stain, empirical antimicrobial therapy based on predisposing and associated conditions, recommendations for specific antibiotic therapy in bacterial meningitis, and recommended doses for antibiotics commonly used in the treatment of bacterial meningitis. This chapter contains 8 figures, 13 tables, 78 references Keywords: Bacterial meningitis, antibiotics, Kernig sign, Brudzinski sign, nuchal rigidity, headache