Evaluating the Impact of the BioFire FilmArray in Childhood Meningitis: An Observational Cohort Study.

BACKGROUND: Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin. METHODS: Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray. RESULTS: The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days). CONCLUSIONS: The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.

Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical Gram-negative bacillary meningitis or ventriculitis: a systematic review and meta-analysis.

PURPOSE: Extensively-drug-resistant Gram-negative bacteria (XDR GNB)-related post-neurosurgical infection is closely related to mortality, which represents a major challenge for neurosurgeons. There is an urgent need to review and evaluate methods to reduce mortality. METHODS: Both international and Chinese databases were searched independently from their inception to 15 June 2023. A meta-analysis was conducted using RevMan 5.4 to compare the efficacy and safety of intravenous (IV) treatment in combination with intrathecal or intraventricular (ITH/IVT) treatment with IV treatment alone for post-neurosurgical meningitis or ventriculitis due to GNB. Mortality, microbiological clearance and adverse events were considered as primary outcomes. RESULTS: In total, 18 eligible studies involving 602 patients were included in the meta-analysis. The IV + ITH/IVT group was associated with significantly lower mortality (especially in the XDR GNB subgroup) and acceptable safety. In terms of microbiological clearance, a significant decrease was shown in the XDR GNB subgroup. Significant benefits were shown in laboratory parameters and clinical symptoms after patients were treated with ITH/IVT. CONCLUSION: Additional ITH/IVT treatment may promote XDR GNB clearance and reduce mortality. In addition, ITH/IVT administration can improve clinical symptoms and cerebrospinal fluid indicators of patients with post-neurosurgical infections. Significantly, ITH/IVT treatment does not increase the incidence of adverse events at the recommended dose.

Reversible deafness and blindness in Cryptococcus gattii meningitis with a ventriculoperitoneal shunt: A case report and literature review.

Cryptococcus gattii (C. gattii) has been considered a leading cause of meningitis in immunocompetent hosts in tropical and subtropical regions. Visual loss is common but hearing impairment is relatively infrequent in C. gattii meningitis. Notably, there have been limited studies on the etiology, and especially therapy of auditory and ocular complications associated with C. gattii meningitis. Here we report a case of reversible deafness and blindness treated with a ventriculoperitoneal shunt (VPS) surgery in C. gattii meningitis. This case indicated that elevated intracranial pressure (ICP) may play a role in the concurrent hearing and vision impairments associated with C. gattii meningitis and the early VPS surgery after the initiation of the antifungal therapy may effectively improve both hearing and vision in this condition.

Mycoplasma hominis Meningitis Diagnosed by Metagenomic Next-Generation Sequencing in a Preterm Newborn: a Case Report and Literature Review.

Mycoplasma hominis is mainly colonized in the genital tract and vertically transmitted to newborns; however, it rarely causes neonatal meningitis. We report a case of M. hominis meningitis in a premature infant. She was admitted to our hospital for treatment after 6 days of repeated fever. After admission, repeated cerebrospinal fluid (CSF) analysis showed that leukocytes and protein in CSF increased substantially and glucose decreased, but there was no growth in conventional CSF culture. The patient was diagnosed with M. hominis meningitis by metagenomic next-generation sequencing (mNGS). The antibiotic therapy used for the neonate was meropenem, vancomycin, and ampicillin against bacterial infection and azithromycin against mycoplasma infection. The child was subsequently considered cured and discharged from the hospital and followed up regularly in the neurology clinic. The mNGS may be a promising and effective diagnostic technique for identifying uncommon pathogens of meningitis in patients with meningitis symptoms and signs without microbial growth in routine CSF culture.

Cerebrospinal fluid analysis in emergency patients with suspected infection of the central nervous system.

BACKGROUND AND PURPOSE: Meningitis and encephalitis are potentially life-threatening diseases that require fast and accurate diagnostics and therapy. The value of polymerase chain reaction (PCR) multiplex testing in clinical practice is still a matter of debate. This study aims to evaluate its benefits and limitations in emergency patients. METHODS: We assessed the value of a meningoencephalitis PCR array in the clinical routine of an emergency department. RESULTS: Of 1578 emergency patients who received a lumbar puncture, 43% received it for a clinically suspected central nervous system (CNS) infection. After initial workup for cerebrospinal fluid (CSF) cell count, protein and glucose, a CNS infection was still considered likely in 307 patients. In these patients, further microbiologic workup was performed. A total of 230 samples were examined by PCR and a pathogen was detected in 66 of these samples. In the case of a positive microbiologic result, a comparison between PCR array and standard method was available for 59 samples, which demonstrated an overcall agreement of 80% (n = 47/59). Of interest, exclusively array-positive results were observed for patients with meningitis found to be positive for Streptococcus pneumoniae; four out of five patients had been treated with antibiotics before the lumbar puncture. In samples with normal CSF cell count only two positive array results were obtained, both for human herpesvirus 6, and these were not clinically relevant. CONCLUSION: Our data suggest that the array substantially contributes to a detection of pathogens in patients with suspected CNS infection and seems of particular interest in patients with acute bacterial meningitis under empiric antibiotic treatment. In CSF samples with normal cell count, it might be dispensable.

COVID-19 and Serious Bacterial Infection in Febrile Infants Less Than 60 Days Old.

INTRODUCTION: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease 2019 (COVID-19) pandemic that drastically impacted the United States. The evidence was not clear on how SARS-CoV-2 infection impacted children, given the high prevalence of SAR-CoV-2 infection. Febrile infants less than 60 days old are an ongoing challenge to risk-stratify for serious bacterial infection (SBI), including urinary tract infection (UTI), bacteremia, and meningitis. We hypothesized there would be a lower rate of SBI in SARS-CoV-2 positive febrile infants compared to those SARS-CoV-2 negative. METHODS: This was a retrospective chart review with a nested, age-matched, case-control study performed from March 2020-June 2021. Infants less than 60 days old presenting with fever were assigned groups based on SARS-CoV-2 infection. Blood, urine, and cerebrospinal fluid cultures were used as the gold standard to diagnose SBI. We compared overall rate of SBI as well as individual rates of SBI between each group. We performed a subgroup analysis evaluating the age group 29-60 days old. RESULTS: A total of 164 subjects met criteria for analysis: 30 COVID-19 positive and 134 COVID-19 negative subjects. Rate of SBI was 17.9% (95% confidence interval [CI]: 11.8-25.5%) in the COVID-19 negative group compared to 0% (95% CI: 0.0%-11.1%) in the COVID-19 group, which demonstrated statistical significance (p = 0.008). In the age-matched data, we found statistical significance for any SBI (p = <0.001). For individual rates of SBI, we found statistical significance for UTI (p = <0.001) and bacteremia (p = <0.001). The 29-60 days-old subgroup analysis did not achieve statistical significance (p = 0.11). CONCLUSION: This study demonstrated the utility of including SARS-CoV-2 infection as part of the risk stratification of febrile infants less than 60 days old. While overall there is a low incidence of bacteremia and meningitis in this age group, these results can contribute to existing literature and potentially help decrease invasive testing and exposure to broad-spectrum antibiotics.

The experience of using FilmArray Meningitis/Encephalitis Panel for the diagnosis of meningitis and encephalitis in pediatric patients.

BACKGROUND/PURPOSE: Central nervous system infections can cause severe complications and even death in children. Early diagnosis of the causative pathogen can guide appropriate treatment and improve outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) is a multiplex polymerase chain reaction (PCR) assay targeting 14 pathogens. We aimed to examine FA-ME performance compared with conventional assays and its effect on antimicrobial usage. METHODS: We prospectively enrolled 55 pediatric patients with suspected meningitis or encephalitis and simultaneously performed FA-ME and conventional assays. Sixty-three hospitalized patients with CNS infection before implementing FA-ME were considered controls. We compared the FA-ME results with conventional assays and the empiric antimicrobial usage and hospital stay between the two study groups. RESULTS: Nine patients (16.4%) tested positive by FA-ME, four were bacterial, and five were viral. Three additional pathogens were detected by conventional assays: Enterococcus faecalis, Leptospira, and herpes simplex virus type 2. In the control group, two bacterial pathogens were detected by CSF culture and four viral pathogens by single PCRs. Compared with the control group, the FA-ME group had a shorter time for pathogen detection, but there were no significant differences in pathogen detection rate, duration of empiric antimicrobial therapy, and length of hospital stay. CONCLUSION: Although no significant difference was found in empiric antimicrobial duration and length of stay between patients tested with FA-ME and conventional assays, FA-ME had the advantage of a shorter detection time and early exclusion of potential causative pathogens. The FA-ME results should be interpreted carefully based on the clinical presentation.

Differential Performance of the FilmArray Meningitis/Encephalitis Assay To Detect Bacterial and Viral Pathogens in Both Pediatric and Adult Populations.

Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.

Integrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics.

The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.

Klebsiella pneumoniae-related brain abscess and meningitis in adults: Case report.

INTRODUCTION: Klebsiella pneumoniae is once thought to be a less common cause of brain abscess in adults and is mainly hospital-acquired. Community-acquired CNS infection (brain abscess and meningitis) caused by K pneumoniae without other metastatic septic abscesses is exceedingly rare. Therefore, we present a rare adult patient with invasive cerebral abscess and meningitis without other invasive abscesses related to K pneumoniae. PATIENT CONCERNS: A 64-year-old woman experienced a sudden onset of severe continuous headache accompanied by intermittent nausea, vomiting, and fever. Meanwhile, she experienced tinnitus and had a feeling of swelling in the right ear. DIAGNOSIS: Cranial magnetic resonance imaging revealed abnormal hyperintensity signals in the left head of the caudate nucleus. The next generation sequencing of cerebral spinal fluid showed infection with K pneumoniae. The patient was diagnosed with K pneumoniae-related brain abscesses and meningitis. INTERVENTIONS: Antibacterial treatment was carried out for 2 months. OUTCOMES: The patient recovered well. CONCLUSION: Despite the progress of modern neurosurgical techniques, new antibiotics, and modern imaging techniques, brain abscesses are still a potentially fatal infection. Streptococci are common organisms that result in brain abscesses. Nevertheless, Klebsiella species, once thought to be a less common cause of brain abscess in adults, has become an increasingly important cause of brain abscess, especially in Asia.

South Asian (Clade I) Candida auris meningitis in a paediatric patient in Iran with a review of the literature.

Candida meningitis is a rare life-threatening yeast infection mostly involving immunocompromised or paediatric patients undergoing neurosurgical procedures or shunt placement. Due to difficulties in diagnosis because of diverse clinical manifestations, the number of patients affected is most likely underestimated. Therefore, the correct diagnosis may be delayed for months, and accurate species identification is highly recommended for administering appropriate antifungal therapy. We report the first case of fluconazole-resistant Candida auris meningitis in a paediatric patient in Iran. This strain was probably imported, as it genotypically belonged to Clade I from South Asia. Furthermore, we include a literature review of C auris meningitis cases, as the number of cases with C auris meningitis has increased with reports from the United Kingdom, India and Iran. This problem might increase further in the era of COVID-19 due to attrition of experienced healthcare personnel and a high workload of hospital healthcare workers. To understand the precise prevalence of this emerging multidrug resistance pathogen, epidemiological surveillance studies are urgently warranted.

Normal Values for Cerebrospinal Fluid in Neonates: A Systematic Review.

BACKGROUND: The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded. METHODS: A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded. RESULTS: We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/µL in preterm and <10 cells/µL in term neonates, the neutrophil count was <16 and 8 cells/µL, and the protein concentration was <210 and 110 mg/dL, respectively. CONCLUSION: The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.

ClpV1 in avian pathogenic Escherichia coli is a crucial virulence factor contributing to meningitis in a mouse model in vivo.

Meningitis associated with avian pathogenic Escherichia coli (APEC) is an infectious disease of poultry that has gained significant attention because of its potential to infect humans. APEC can utilize two type Ⅵ secretion systems (T6SSs) to efficiently transport toxin effectors into hosts. ClpV1 is one of the core components of the T6SS1. To our knowledge, it has not been clarified how the clpV1 gene contributes to the pathogenicity of meningitis-associated APEC. To investigate the function of the clpV1 gene in the process of Escherichia coli meningitis, a mutant TW-XMΔclpV1 strain was constructed and characterized. In this study, the clpV1 deleted strain displayed a significant decrease in both motility and biofilm formation as well as a reduction in the expression of virulence genes fliC, luxS and ibeA. In vivo studies using mouse and duck models found that the clpV1 deleted groups showed decreased proliferation, fewer lesions and lower expression of inflammatory cytokines in the brain suggesting that clpV1 is involved in the pathogenicity of TWXM. Besides, the decreased quantity of Evans Blue (EB) and the down-regulation of tight junctions (TJs) proteins in the mouse clpV1 deleted group demonstrating a more intact blood-brain barrier (BBB). In conclusion, these results suggest that the clpV1 gene is associated with motility and biofilm formation of TWXM strain and contributes to meningitis by damaging the BBB and brain tissues.

Higher incidence of prescribing rates and utilization of broad spectrum cephalosporin in young patients: A retrospective observational study in a tertiary care hospital.

Frequent use of antibiotics has been developed resistance and the use of broad spectrum cephalosporin must be limited in children. The study evaluated the association of prescribing patterns of third generation cephalosporin with diagnosis, age, availability of cultural sensitivity report and gender. It is an observational study that was carried out in the duration of six months in a low socio-economic tertiary care hospital. The data of six hundred and eighty-five (685) patients were collected from the medical records of the tertiary hospital. The cephalosporin are the most prescribed antibiotics in children 118/217 (54.3%) followed by adults 119/403 (29.5%) and teenagers 18/65 (27.6%). Whereas, 75/217 (34.5%), 126/403 (31.2%) and 22/65 (33.8%) were prescribed cephalosporin with combination in patients respectively. The culture sensitivity was performed only in 25% of patients i.e., 173/685, Of 173 culture reports 70 and 91 cases from children and adults respectively. Blood is mostly examined specimen in children and urine in adults. Escherichia coli was highly recovered pathogen in culture sensitivity report. The study concluded broad spectrum cephalosporin antibiotics were highly prescribed in children. The culture sensitivity was performed in limited number of patients. Antibiotics stewardship programme will be implemented to reduce the prescribing of broad spectrum cephalosporin in young patients.

A rare case of meningitis and septicemia caused by Streptococcus suis in a woman without a history of live pig contact or eating raw pork.

Streptococcus suis (S. suis) is a zoonotic pathogen that primarily inhabits the upper respiratory tract of pigs. Therefore, pigs that carry these pathogens are the major source of infection. Most patients are infected through contact with live pigs or unprocessed pork products and eating uncooked pork. S. Suis mainly causes sepsis and meningitis. The disease has an insidious onset and rapid progress. The patient becomes critically ill and the mortality is high. In this case report, we described a rare case of S. suis isolated from a middle-aged woman in Jinhua City, Zhejiang Province, China, who did not have any contact with live pigs and had not eaten uncooked pork. S. Suis was isolated from both the patient's blood and cerebrospinal fluid samples.

A rare case of extensively drug-resistant Salmonella typhi meningitis in a 9-year old: a case report.

Meningitis caused by Salmonella typhi is rare and is generally seen in infants. We report a case of a 9-year-old boy with extensively drug-resistant S. typhi meningitis. The patient was diagnosed using a culture sensitivity test and successfully treated with meropenem. Culture sensitivity may be included in routine testing for the diagnosis of S. typhi especially in developing countries due to high burden of disease and emergence of drug resistance.

Survival patterns of Streptococcus suis serotypes 1 and 14 in porcine blood indicate cross-reactive bactericidal antibodies in naturally infected pigs.

Streptococcus suis serotype (cps) 1 and cps14 have been detected in association with severe diseases such as meningitis and polyarthritis in pigs. Though these two cps are very similar, only cps14 is an important zoonotic agent in Asia and only cps1 is described to be associated with diseases in suckling piglets rather than weaning piglets. The main objective of this study was to assess restriction of survival of cps14 and cps1 in porcine blood by IgG and IgM putatively cross-reacting with these two cps. Furthermore, we differentiate recent European cps1/14 strains by agglutination, cpsK sequencing, MLST and virulence-associated gene profiling. Our data confirmed cps1 of clonal complex 1 as an important pathotype causing polyarthritis in suckling piglets in Europe. The experimental design included also bactericidal assays with blood samples drawn at different ages of piglets naturally infected with different S. suis cps types including cps1 but not cps14. We report survival of a cps1 and a cps14 strain (both of sequence type 1) in blood of suckling piglets with high levels of maternal IgG binding to the bacterial surface. In contrast, killing of cps1 and cps14 was recorded in older piglets due to an increase of IgM as demonstrated by specific cleavage of IgM. Heterologous absorption of antibodies with cps1 or cps14 is sufficient to significantly increase the survival of the other cps. In conclusion, IgM elicited by natural S. suis infection is crucial for killing of S. suis cps1 and cps14 in older weaning piglets and has most likely the potential to cross-react between cps1 and cps14.