Central Nervous System Infection Research Articles

B-078 Prevelance of Autoimmune Factors in Patients with Seizures of Unknown Etiology in Western China

Abstract Objective To delineate the features of autoantibody in patients with seizure of unknown etiology in Western China and to analyze other potential risk factors of an epileptic seizure. Methods From January 2017 to June 2022, 639 patients with unexplained seizure were assessed retrospectively. Neuronal autoantibodies were assessed in 471 individuals, including 12 common neural-specific autoantibodies, antibodies against four common pathogens associated with central nervous system infections, or neurophagocytosis, and two thyroid-related autoantibodies. Results Sixty-nine patients were positive for neural-specific autoantibodies in CSF and serum. Among the patients, 32 (46.38%) expressed NMDAR-Ab, 14 (20.29%) expressed GABABR-Ab, 10 (14.49%) expressed LGI1-Ab, 7 (10.14%) expressed GFAP-Ab, 3 (4.34%) expressed Yo-Ab, 2 (2.90%) expressed CASP2-Ab, and 1 (1.45%) expressed Hu-Ab. Compared to patients with non-autoimmune epileptic seizure, the positive rates of thyroid-related antibody expression and the neurophagocytosis pathogen levels of HSV-IgG and T. gondii-IgG were significantly different in patients with autoimmune epileptic seizure. Conclusion This study elucidated the antibody status of autoimmune epilepsy in western China, allowing for better identification and diagnosis of autoimmune epilepsy in the future.

Enteroviral central nervous system infections in patients with Lyme neuroborreliosis

Patients with Lyme neuroborreliosis (LNB) are rarely tested for the presence of neurovirulent viruses other than tick-borne encephalitis virus (TBEV); however, such coinfections could be of clinical importance. The aim of the study was to search for the presence of neurotropic viruses in a LNB patients.Fourteen patients admitted with signs and symptoms of neuroinfection who were eventually diagnosed to have LNB (according to the guidelines of the European Federation of Neurological Societies) were subjects of the study. Sera and cerebrospinal fluid (CSF) collected at the time of initial presentation were tested for viral pathogens most common in our geographical area: human enteroviruses (EV), herpes simplex virus type 1 and 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus type 6, human adenoviruses, and TBEV using PCR/RT-PCR and serological assays. RNA and DNA-based metagenomic next-generation sequencing (mNGS) was used to detect other viral pathogens.EV was detected in CSF from two (14 %) LNB patients and viral loads were similar (220 and 270 copies/ml). The mMGS analysis were performed on CSFs from 10 patients and generated a total 213,750,885 NGS reads, 0.05 % of which were viral. However, none of potential pathogens fulfilled the criteria for positive viral detection by mNGS.Using a number of PCR/RT-PCR assays and mNGS we identified EV infection in two out of 14 LNB patients. The possible co-occurrence of enterovirus and Lyme neuroborreliosis infections may warrant further research.

Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study

BackgroundAcute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%.MethodsInclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey.ResultsEleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate.ConclusionsEven in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.

Spontaneous Clostridium perfringens Meningitis and Brain Abscess in a Neonate.

This case describes a neonate who presented with spontaneous Clostridium perfringens meningitis and brain abscess. The abscess was drained, and the infant completed a 6-week course of antibiotics. Throughout this time the infant remained well with no need for intensive care. C. perfringens central nervous system infections are associated with trauma and poor outcomes. This case highlights that the spectrum of disease can include spontaneous infection with a relatively mildly clinical course demonstrating the importance of 16s polymerase chain reaction in culture-negative cases and its role in detecting rare causes of central nervous system infections such as C. perfringens .

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.

Prevalence of dementia and its association with central nervous system infections among older persons in northern Uganda: cross-sectional community-based study

BackgroundDementia is a condition in which there is deterioration in cognitive function beyond what might be expected from the usual consequence of biological aging. Few studies have been conducted on the prevalence of dementia and its association with central nervous system (CNS) infections among older persons in African settings, particularly in Uganda. Therefore, this study assessed the prevalence of dementia and its association with CNS infections among older persons in Lira District, northern Uganda.MethodsThis was a cross-sectional community-based study in Lira district northern Uganda. The study was conducted in March 2022 among 434 older persons aged 50 and above years who were selected by multistage sampling. Data were collected using an interviewer-administered questionnaire supplemented with information from participant’s medical records and a brief community screening instrument for dementia. The instrument classifies dementia into unlikely, probable or possible dementia. Data were entered in duplicate into EpiData version 3.0, then transferred to Statistical Package for Social Sciences (SPSS) version 23 for statistical analysis.ResultsOur study found almost one in four (23%) of the older persons in Lira district northern Uganda were suffering from probable or possible dementia. Our study further found that older persons in Lira district northern Uganda with a positive history of central nervous system infections (CNS) had nearly five times higher odds of having probable or possible dementia compared to their counterparts (cOR: 4.5; 2.76–7.23; p ≤ 0.001). Being in advanced age of 70 + years (aOR: 2.6; 1.6–4.3; p ≤ 0.001), positive history of CNS infection particularly Herpes simplex virus-1 (aOR: 5.4; 1.4–20.5; p = 0.013), and chronic headache (aOR: 1.9; 1.1–3.1; p = 0.019) were independent predictors of probable or possible dementia among participants in this study.Conclusion and recommendationsDementia is a common condition among older persons in Lira district northern Uganda with a prevalence of 23% in our study. Older persons with a positive history of CNS infection had higher odd of developing dementia compared to their counterparts. Having advanced age, cerebral malaria, Herpes simplex virus − 1 (HSV-1) infections, and chronic headache were independent predictors for dementia. These results imply that health assessment for the risk of dementia should include screening for history of CNS conditions particularly cerebral malaria, HSV-1 and chronic headache.

The participation of clinical pharmacists in the treatment of patients with central nervous system infection can improve the effectiveness and appropriateness of anti-infective treatments: a retrospective cohort study.

Background: Central nervous system infection (CNSI) treatment in hospital neurosurgery emphasizes the importance of optimizing antimicrobial therapy. Timely and appropriate empiric antibiotic treatment is critical for managing patients with bacterial meningitis. Objectives: To evaluate the activities of clinical pharmacists in the anti-infective treatment of patients with CNSI in neurosurgery. Method: A single-center retrospective cohort study was carried out from January 2021 to March 2023 at a tertiary teaching hospital in China. The study sample included a group that received pharmacy services and a group that did not. In the pharmacy services group, the anti-infective treatment plan was led and developed by pharmacists. Pharmaceutical care, including medication therapy and all CNSI treatment regimens, was administered in daily unit rounds by pharmacists. Baseline demographics, treatment outcomes, and rational use of antibiotics were compared between the two groups, and the impact of a antimicrobial stewardship (AMS) program was evaluated. Results: Of the 306 patients assessed according to the inclusion and exclusion criteria, 151 patients were included, and 155 patients were excluded due to abnormal data and missing information on antibiotic costs or antimicrobial use. Eventually, 73 were included in the pharmacy services group and 78 in the group without pharmacist participation. The antibiotic use density (AUD) of the pharmacy services group decreased from 167.68 to 127.63 compared to the group without pharmacist participation. After the pharmacist services, the AUD for linezolid decreased from 9.15% to 5.23% and that for miscellaneous agents decreased from 17.91% to 6.72%. The pharmacy services group had better improvement (p < 0.05) and a significantly higher score for the rational use of antibiotics (p < 0.05) than the group without pharmacist participation. Conclusion: The clinical pharmacist services evaluation results demonstrated an essential role of clinical pharmacist-led AMS programs in the effective and appropriate use of anti-infective treatments in neurosurgery with patients with CNSI.

Brain-Derived Exosomal miRNA Profiles upon Experimental SAE Rats and Their Comparison with Peripheral Exosomes.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction secondary to body infection without overt central nervous system infection. Dysregulation of miRNA expression in the transcriptome can spread through RNA transfer in exosomes, providing an early signal of impending neuropathological changes in the brain. Here, we comprehensively analyzed brain-derived exosomal miRNA profiles in SAE rats (n = 3) and controls (n = 3). We further verified the differential expression and correlation of brain tissue, cerebrospinal fluid, and plasma exosomal miRNAs in SAE rats. High-throughput sequencing of brain-derived exosomal miRNAs identified 101 differentially expressed miRNAs, of which 16 were downregulated and 85 were upregulated. Four exosomal miRNAs (miR-127-3p, miR-423-3p, mR-378b, and miR-106-3p) were differentially expressed and correlated in the brain tissue, cerebrospinal fluid, and plasma, revealing the potential use of miRNAs as SAE liquid brain biopsies. Understanding exosomal miRNA profiles in SAE brain tissue and exploring the correlation with peripheral exosomal miRNA can contribute to a comprehensive understanding of miRNA changes in the SAE pathological process and provide the possibility of establishing early diagnostic assays.

Comparison of two assays to diagnose herpes simplex virus in patients with central nervous system infections.

Multiplex PCR panels are frequently used for detecting the diagnosis of central nervous system infection, but have demonstrated lower sensitivity for herpes simplex virus (HSV) compared to targeted PCRs. Providers in our institution frequently order both multiplex (BioFire Meningitis/Encephalitis Panel (MEP)) and targeted HSV PCR (Diasorin Simplexa HSV-1/2 Direct), allowing comparison of assay performance in practice and a unique clinical characterization of patients with concordant positive or discordant results. We retrospectively analyzed all HSV testing performed using the two assays simultaneously in a large multi-center institution between 12/10/2018 and 6/6/2022. We described and compared laboratory, diagnostic and therapeutic data between patients with positive results on both assays with patients with discordant results. 1,387 patients were tested with both assays, of which 25 were positive on at least one assay. Eleven (44%) had discordant results; 9 were targeted-PCR-positive/MEP-negative and 2 were targeted-PCR-negative/MEP-positive. Compared with patients with concordant positive results, discordant targeted PCR-positive/MEP-negative patients had a higher PCR cycle threshold value (i.e., >35) and milder illness characterized by lower CSF WBC counts (4vs 152; p=0.032), fewer MRI abnormalities (37.5% vs. 87.5%; p=0.039), HSV meningoencephalitis as primary discharge diagnosis (33% vs. 100%; p<0.0001) and were more often treated with oral medication or none at all. Patients with discordant targeted PCR-positive/MEP-negative results represent a population with milder clinical disease. These findings will help clinicians and laboratorians determine when both targeted HSV and multiplex assays should be performed simultaneously and identify patients for whom a multiplex PCR may suffice, despite lower assay sensitivity.

METHODOLOGICAL APPROACHES TO THE VERIFICATION OF CAUSES OF INFECTIOUS DISEASES IN EMERGENCIES

Emergency situations (ES) of various genesis are accompanied by a change in the epidemic state of the territory and population, which requires the timely detection of an infectious striking factors (pathogenic biological agents and toxins) and non-infectious agents. The laboratory network is an important component in the emergency response system, which allows determining the etiology of infectious and parasitic diseases, treating of patients; directions of anti-epidemic support, effectiveness of measures.&#x0D; The aim of the study is to evaluate modern models of laboratory support for the indication of pathogenic biological agents (PBA), the tasks of the laboratory service at the main stages of an emergency: readiness, response and recovery.&#x0D; Laboratory diagnostics is an important component in the system of protection during emergencies, which ensures the detection of PBA and toxins, conducting clinical laboratory tests. The scope and directions of activity of the laboratory network are determined by the real situation and differ at the stages of readiness, response and recovery at ES.&#x0D; The indication of PBA begins at the stage of carrying out sanitary-epidemiological reconnaissance in the affected territories. The PBA detection and identification can be carried out by the laboratory network of health care institutions in the emergency zone, mobile laboratories of various types, and the laboratory network outside the affected areas. The methods of antigens detection based on an immune capture assay (enzyme-linked immunosorbent assay, fluorescent microscopy), spectroscopy as well as PBA genomes (multiplex PCR) allows to verify the diagnoses of infectious patients in up to 2 hours. In the case of using lateral flow chromatography, it is advisable to use sets of rapid tests taking into account the group of infections: intestinal, respiratory, contact, blood. Normally is the use of other principles of kit selection: group of particularly dangerous infections; sexually transmitted infections; central nervous system infections, etc.

Sex Differences in Neurological Emergencies Presenting to Multiple Urban Level 1 Trauma Centers.

Previous studies have suggested that there are sex differences in the treatment and outcome of neurological emergencies; however, research identifying the role these sex differences play in the management of neurological emergencies is lacking. More knowledge of the way sex factors into the pathophysiology of neurological emergencies will be helpful in improving outcomes for these patients. The aim of this cross-sectional study was to assess the prevalence and management of neurological emergencies while evaluating sex differences in the diagnosis and treatment of these emergencies. We analyzed a cohort of 530 adult patients from four level 1 trauma centers over a period of 4 weeks who had a chief complaint of a neurological emergency, including seizures, cerebrovascular events, headache disorders, traumatic brain injuries, and central nervous system infections. Among patients with neurological emergencies, a significantly lower proportion of female patients underwent neurosurgery and were admitted to the intensive care unit compared to male patients, but there were no significant differences between sexes in the time of symptom onset, type of hospital transportation, amount of neuroimaging performed, admission rates, hospital length of stay, and disposition from the emergency department. Although female patients were more likely to have a chief complaint of headache compared to traumatic injuries in male patients, this was not statistically significant. A significantly higher proportion of female patients had health insurance coverage than male patients.

Rare Presentation of Morganella morganii Microorganism as Epidural and Subdural Empyema

Abstract Background Morganella morganii is a gram-negative bacterium that rarely infects the central nervous system (CNS). Few reports described such an infection in the CNS. We present a case of extremely invasive M. morganii infection in the CNS. In addition, we performed a literature review of M. morganii infection in the CNS. Case report A 53-year-old male was admitted to the hospital due to fever, general weakness, and left-sided facial muscle twitching. He had a history of diabetes mellitus, hypertension, brain tumor, and epilepsy. Multiple left frontal scalp ulcers were revealed. In addition, a computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed a left side epidural abscess and subdural empyema. Moreover, the patient had left frontal bone osteomyelitis. The next day, the patient underwent craniectomy, was transferred to the intensive care unit and started an empirical antibiotic course. Morganella morganii was identified from the infected scalp ulcers. On the 13th day, the patient passed away due to uncontrolled status epilepticus. Conclusion M. morganii can cause isolated or multiple types of CNS infections, including brain abscess, meningitis, and subdural empyema. The mortality rate may differ according to age and to the use of surgical evacuation.

Analysis of tigecycline in the cerebrospinal fluidand serum of patients with Acinetobacter baumannii central nervous system infection.

Aim: This study aimed to establish a method to determine tigecycline (TGC) in the cerebrospinal fluid (CSF) and serum of 12 patients with multidrug-resistant Acinetobacter baumannii (MDRAB) central nervous system infection (CNSI) and evaluate the correlation of TGC in CSF and serum samples. Materials & methods: TGC in CSF and serum was detected by high-performanceliquid chromatography with tandem mass spectrometry. Results: In all12 patients, the CSF-to-serum ratio of TGC at asteady-state trough concentration ranged from 21.46to 44.46%, and the mean value was 31.61±8.13%. The correlation of TGC in CSF and serum was 0.5065. Conclusion: CNSI might have no potential to increase the penetration ability of TGC into theCSF. The correlation between the concentrations of TGC in CSF and serum at steady state was demonstrated to be positive.

Investigation of risk factors for external ventricular drainage‑associated central nervous system infections in patients undergoing neurosurgery.

Meningitis/ventriculitis (MV) is an illness which can occur as a complication following neurosurgical procedures. Devices such as an external ventricular drain (EVD) are also related to considerable complications, such as infections. The present study examined the risk factors associated with central nervous system (CNS) infections associated with the external ventricle drainage system. The present retrospective study included all patients hospitalized between April, 2011 and August, 2018 who had been receiving therapy with EVD for developed hydrocephalus. A total of 48 out of 65 patients were classified into two groups as follows: Patients without MV (group A) and patients who developed MV (group B). The durations of hospital stay and intensive care unit (ICU) stay were significantly lower in group A (32.4±24 and 21.1±11 days, respectively) compared to group B (54.7±37 and 42±24 days, respectively) (P=0.027 and P=0.001, respectively). The Acute Physiological and Chronic Health Evaluation II (APACHE II) score and EVD distance from the wound exit side to the burr hole were significantly lower in the survivors compared to the non-survivors (17.5±6 and 15.4±4 vs. 22.5±6 and 39.8±38, respectively). Receiver operating characteristic analysis revealed that the APACHE II score with an area under the curve [(AUC) of 0.677, P=0.044, and 95% confidence interval (CI) of (0.516-0.839)] and a cut-off value of 14 could predict mortality with a sensitivity of 100% and a specificity of 71%; the EVD distance from the wound exit side from the burr hole with an AUC of 0.694 (P=0.028), 95% CI of 0.521-0.866 and a cut-off value of 11.5 mm could predict mortality with a sensitivity of 88% and a specificity of 83%. On the whole, the present study demonstrates that the EVD-related distance from the wound exit side of the burr hole can predict poor outcomes due to CNS infections in patients undergoing neurosurgery.

Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase-negative staphylococcus.

Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates. The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models. This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS). Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution's vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis. A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

The clinical utility of metagenomic next-generation sequencing for the diagnosis of central nervous system infectious diseases.

To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system infections (CNSI). Cerebrospinal fluid (CSF) from 54 patients who were high-level clinical suspicion of CNSI was collected and sent for mNGS and conventional tests from January 2019 to March 2022. Twenty out of 54 patients were diagnosed with CNSI and 34 non-CNSI. Among the 34 non-CNSI, one was false positive by mNGS. Among the 20 CNSI, 11 had presumed viral encephalitis and/or meningitis, 5 had presumed bacterial meningitis, 2 had presumed TMB, 1 had Crytococcus meningitis and 1 had neurosyphilis. The sensitivity of viral encephalitis and/or meningitis was 0.73 (8/11); 10 virus were detected; 9/10 was dsDNA; 1/10 was ssRNA. SSRN ranged from 1 to 13. The accuracy rate was 0.4, the accuracy rate was positively correlated with SSRN (r = 0.738, P = 0.015), SSRN ≥ 1, the accuracy rate was 0.4; SSRN ≥ 3, the accuracy rate was 0.66; SSRN ≥ 4, the accuracy rate was 0.75; SSRN ≥ 6, the accuracy rate was 1. The sensitivity of bacterial meningitis was 1. Seven kinds of bacteria were detected, among which 3/7 were gram positive, 3/7 were gram negative, and 1/7 was infected NTM (nontuberculous mycobacteria). The accuracy rate was 0.43 (3/7). The sensitivity of TBM was 0.66 (2/3), the accuracy rate was 1. The sensitivity of Crytococcus meningitis was 1, the accuracy rate was 0.5. PPV (positive predictive value) of mNGS was 0.94, NPV (negative predictive value) of mNGS was 0.89, specificity was 0.97 and sensitivity was 0.8. The AUG for CSF mNGS diagnosis of CNSI was 0.89 (95% CI = 0.78-0.99) Headache, meningeal irritation sign and image of meninges abnormal were correlated with the sensitivity of mNGS (r = 0.451, 0.313, 0.446; p = 0.001, 0.021, 0.001); CSF Glucose and CSF Chloride were negatively correlated with sensitivity of mNGS (r = -0.395, -0.462; p = 0.003, ＜ 0.001). mNGS is a detection means with high sensitivity, wide coverage and strong timeliness, which can help clinicians to identify the pathogen diagnosis quickly, conduct targeted anti-infection treatment early and reduce antibiotic abuse. The pathogen which causing low CSF Glucose, low CSF Chloride or meninges infections was more likely to be detected by mNGS. It may be related to growth and structural characteristics of the pathogen and blood-brain barrier damage.

Clinical and microbiological characteristics of carbapenem-resistant Enterobacteriaceae causing post-operative central nervous system infections in China

ObjectivesPostoperative central nervous system infections (PCNSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) frequently result in unfavourable outcomes. However, CRE PCNSIs have not been well described from a clinical and microbiological perspective. MethodsA total of 254 PCNSIs cases were included (January 2017 through June 2020), and clinical features were compared based on pathogenic classification. Cox regression analysis was performed to assess risk factors for mortality. Antibiotic susceptibility testing and whole genome sequencing were conducted on CRE isolates preserved. MLST, cgMLST, resistance genes and virulence genes were further analysed. ResultsAmong 254 PCNSI cases, 15.4% were caused by Enterobacteriaceae including 28 cases by CRE. The 28-day mortality rates for CRE, CSE and non-Enterobacteriaceae PCNSIs were 50.0%, 27.3%, and 7.4%, respectively. 42.9% (12/28) of the CRE PCNSIs patients achieved clinical cure, with 25.0% achieved microbiological clearance. ST11-KL64 carrying blaKPC-2 was dominant in CRE (17/23, 73.9%), and the 28-day mortality rate of its infection was 58.5%. Most CRKP carried rampA/rampA2 genes (17/23, 73.9%). ConclusionST11-KL64 CRKP carrying blaKPC-2 dominated among CRE PCNSIs. Targeted anti-infective combination therapy based on ceftazidime/avibactam or amikacin, combined with intrathecal administration of amikacin, was found to be effective. These findings render a new insight into the clinical and microbiological landscape of CRE PCNSIs.

A case of meningitis caused by Ralstonia insidiosa, a rare opportunistic pathogen

BackgroundRalstonia is a genus of Gram-negative opportunistic bacteria that can survive in many kinds of solutions and cause a variety of infections. Ralstonia spp. have increasingly been isolated and reported to cause infections in recent years, thanks to the development of identification methods such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and gene sequencing. However, infections caused by Ralstonia insidiosa are still rare. Only a few cases of respiratory infections and bloodstream infections have been reported, none of which involved meningitis. To the best of our knowledge, this is the first reported case of meningitis caused by R. insidiosa worldwide. It is necessary to report and review this case.Case presentationWe report a case of meningitis caused by R. insidiosa following lumbar surgery in China. The patient exhibited symptoms of headache, dizziness, and recurrent fever. The fever remained unresolved after empiric antibiotic therapy with intravenous cefotaxime and vancomycin in the initial days. Cerebrospinal fluid (CSF) culture yielded Gram-negative non-fermentative bacteria, which were identified as R. insidiosa. As there was a lack of antibiotic susceptibility testing results, clinical pharmacists conducted a literature review to select appropriate antibiotics. The patient’s condition improved after receiving effective treatment with intravenous cefepime and levofloxacin.ConclusionsUncommon pathogens, such as R. insidiosa, should be considered in postoperative central nervous system (CNS) infections, particularly in cases with unsatisfactory results of empiric anti-infective therapy. This is the first reported case of meningitis caused by R. insidiosa worldwide. MALDI-TOF MS provides rapid and accurate identification of this pathogen. The antibiotic susceptibility testing results of R. indiosa may be interpreted based on the breakpoints for Pseudomonas spp., Burkholderia cepacia spp., and Acinetobacter spp. Our case presents a potential option for empiric therapy against this pathogen, at least in the local area. This is crucial to minimize the severity and mortality rates associated with meningitis. Standardized antibiotic susceptibility testing and breakpoints for the Ralstonia genus should be established in the future as cases accumulate. Cefepime and levofloxacin may be potential antibiotics for infections caused by R. indiosa.

Pathogenesis and outcome of VA1 astrovirus infection in the human brain are defined by disruption of neural functions and imbalanced host immune responses.

Astroviruses (AstVs) can cause of severe infection of the central nervous system (CNS) in immunocompromised individuals. Here, we identified a human AstV of the VA1 genotype, HAstV-NIH, as the cause of fatal encephalitis in an immunocompromised adult. We investigated the cells targeted by AstV, neurophysiological changes, and host responses by analyzing gene expression, protein expression, and cellular morphology in brain tissue from three cases of AstV neurologic disease (AstV-ND). We demonstrate that neurons are the principal cells targeted by AstV in the brain and that the cerebellum and brainstem have the highest burden of infection. Detection of VA1 AstV in interconnected brain structures such as thalamus, deep cerebellar nuclei, Purkinje cells, and pontine nuclei indicates that AstV may spread between connected neurons transsynaptically. We found transcriptional dysregulation of neural functions and disruption of both excitatory and inhibitory synaptic innervation of infected neurons. Importantly, transcriptional dysregulation of neural functions occurred in fatal cases, but not in a patient that survived AstV-ND. We show that the innate, but not adaptive immune response was transcriptionally driving host defense in the brain of immunocompromised patients with AstV-ND. Both transcriptome and molecular pathology studies showed that most of the cellular changes were associated with CNS-intrinsic cells involved in phagocytosis and injury repair (microglia, perivascular/parenchymal border macrophages, and astrocytes), but not CNS-extrinsic cells (T and B cells), suggesting an imbalance of innate and adaptive immune responses to AstV infection in the brain as a result of the underlying immunodeficiencies. These results show that VA1 AstV infection of the brain in immunocompromised humans is associated with imbalanced host defense responses, disruption of neuronal somatodendritic compartments and synapses and increased phagocytic cellular activity. Improved understanding of the response to viral infections of the human CNS may provide clues for how to manipulate these processes to improve outcomes.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.