BACKGROUND AND OBJECTIVE

Accurately diagnosing bacterial meningitis and ventriculitis in children is challenging due to nonspecific symptoms and the lack of specificity in conventional CSF parameters. Cerebrospinal fluid (CSF) procalcitonin (PCT) is a promising diagnostic marker but studies on its utility in children are lacking. We aimed to assess the diagnostic value of CSF procalcitonin for bacterial meningitis and ventriculitis in children and establish a clinically relevant cut-off level.

A total of 131 patients were included in the study, and the CSF PCT levels were measured in two groups. Group 1 comprised of patients with bacterial meningitis and ventriculitis (n=21), while Group 2 consisted of patients with tuberculous meningitis, fungal meningitis, viral encephalitis, autoimmune encephalitis, central nervous system (CNS) leukemia, and non-infectious or inflammatory CNS conditions (n=110).

CSF PCT demonstrated an area under the curve of 96.57% in the receiver operating characteristic analysis. With a cut-off of 0.19 ng/mL, it achieved high sensitivity (90.48%) and specificity (91.82%), making it an excellent test for distinguishing between bacterial meningitis and ventriculitis from control diseases.

CSF procalcitonin is highly effective in distinguishing pediatric bacterial meningitis and ventriculitis. Especially in clinical scenarios where the conventional laboratory tests are inconclusive, it can complement clinical assessment to diagnose CNS infections accurately and guide prudent antibiotic use.

Objective Varicella-zoster virus (VZV) is the common causes of viral infection of the central nervous system（CNS）,Its clinical manifestations are varied,Summary and analysis of its clinical manifestations and outcomes are helpful for early recognition, guidance of treatment and prognosis. Methods A retrospective analysis was performed for the 11 patients with CNS-VZV infection who were diagnosed and treated in Department of Neurology，Peking Union Medical College Hospital，from 2014 to 2021 to analyze their clinical features and prognosis，and modified Rankin Scale（mRS）was used for evaluation. Results Among the 11 patients，there were 7 male patients（63.63%）and 4 female patients（36.36%）. As for clinical phenotypes，there were 4 patients with meningitis（36.36%），3 patients with limbic encephalitis（27.27%），3 patients with cerebral vasculitis（27.27%），and 1 patient with myelitis（9.09%）. Three patients（27.27%）had acute rash of herpes zoster. The patients had a median cerebrospinal fluid（CSF）pressure of 165（85，330）mmH2O，a median CSF white blood cell count of 46（9，471）×106/L，a median CSF protein quantification of 0.85（0.32，3.12）g/L，and a CSF glucose level of 3.0（2.5，4.0）mmol/L. There was a significant change in mRS score after treatment [3（1，5）vs 0（0，6），P<0.05]. Conclusion The main clinical phenotypes of CSF-VZV infection include meningitis，limbic encephalitis，cerebral vasculitis，and myelitis，among which meningitis tends to have a good prognosis，and the patients with immunosuppressive conditions tend to have a poor prognosis after VZV cerebral vasculitis. CSF mNGS is an important experiment for the confirmed diagnosis of VZV.
Meningitis

Child ; Humans ; Consensus ; Meningitis, Bacterial/therapy*

Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (OR_adjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (OR_adjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (OR_adjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.
Infant ; Male ; Female ; Pregnancy ; Infant, Newborn ; Humans ; Prospective Studies ; Coagulase ; Infant, Extremely Low Birth Weight ; Sepsis/epidemiology* ; Bronchopulmonary Dysplasia ; Escherichia coli ; Infant, Extremely Premature ; Meningitis

Objective: To understand the characteristics of bacterial meningitis after pediatric neurosurgical procedures. Methods: This was a retrospective observational study. From January 2016 to December 2022, 64 children diagnosed with post-neurosurgical bacterial meningitis based on positive cerebrospinal fluid (CSF) culture in Department of Neurosurgery of Shanghai Children's Medical Center were selected as the study population. The clinical characteristics, onset time, routine biochemical indexes of cerebrospinal fluid before anti infection treatment, bacteriology characteristics and sensitivity to antibiotics of bacteria cultured from cerebrospinal fluid were analyzed. Based on the CSF culture results, the patients were divided into the Gram-positive bacteria infection group and the Gram-negative bacteria infection group. The clinical characteristics of the two groups were compared using t-tests or Wilcoxon rank-sum tests, and chi-square tests. Results: There were 64 children,42 boys and 22 girls, with onset age of 0.83 (0.50, 1.75) years. Seventy cases of post-neurosurgical bacterial meningitis occurred in the 64 children, of which 15 cases (21%) in spring, 23 cases (33%) in summer, 19 cases (27%) in autumn, and 13 cases (19%) in winter. The time of onset was 3.5 (1.0, 10.0) months after surgery; 15 cases (21%) occurred within the first month after the surgery, and 55 cases (79%) occurred after the first month. There were 38 cases (59%) showing obvious abnormal clinical manifestations, fever 36 cases (56%), vomiting 11 cases (17%). Forty-eight cases (69%) were caused by Gram-positive bacteria, with Staphylococcus epidermidis 24 cases; 22 cases (31%) were caused by Gram-negative bacteria, with Acinetobacter baumannii the prominent pathogen 7 cases. The Gram-positive bacterial infection was more common in summer than the Gram-negative bacterial infection (20 cases (42%) vs. 3 cases (14%), χ²=5.37, P=0.020), while the Gram-negative bacterial infection was more in autumn and within the first month after surgery than the Gram-positive bacterial infection (11 cases (50%) vs. 8 cases (17%), 15 cases (67%) vs. 5 cases (33%), χ²=8.48, 9.02; P=0.004, 0.003). Gram-positive bacteria resistant to vancomycin and Acinetobacter baumannii resistant to polymyxin were not found. However, Acinetobacter baumannii showed only 45% (10/22) susceptibility to carbapenem antibiotics. Conclusions: The clinical presentation of post-neurosurgical bacterial meningitis in children is atypical. Gram-positive bacteria are the main pathogens causing post-neurosurgical bacterial meningitis; Gram-negative bacterial meningitis are more likely to occur in autumn and within the first month after surgery. Acinetobacter baumannii has a high resistance rate to carbapenem antibiotics, which should be taken seriously.
Male ; Female ; Humans ; Child ; China/epidemiology* ; Anti-Bacterial Agents/pharmacology* ; Meningitis, Bacterial/diagnosis* ; Gram-Negative Bacterial Infections/drug therapy* ; Gram-Positive Bacteria ; Gram-Positive Bacterial Infections/drug therapy* ; Carbapenems ; Retrospective Studies ; Microbial Sensitivity Tests ; Drug Resistance, Bacterial

INTRODUCTION: Differentiating infants with serious bacterial infections (SBIs) or invasive bacterial infections (IBIs) from those without remains a challenge. We sought to compare the diagnostic performances of single biomarkers (absolute neutrophil count [ANC], C-reactive protein [CRP] and procalcitonin [PCT]) and 4 diagnostic approaches comprising Lab-score, Step-by-Step approach (original and modified) and Pediatric Emergency Care Applied Research Network (PECARN) rule. METHOD: This is a prospective cohort study involving infants 0-90 days of age who presented to an emergency department from July 2020 to August 2021. SBIs were defined as bacterial meningitis, bacteraemia and/or urinary tract infections. IBIs were defined as bacteraemia and/or bacterial meningitis. We evaluated the performances of Lab-score, Step-by-Step (original and modified) and PECARN rule in predicting SBIs and IBIs. RESULTS: We analysed a total of 258 infants, among whom 86 (33.3%) had SBIs and 9 (3.5%) had IBIs. In predicting SBIs, ANC ≥4.09 had the highest sensitivity and negative predictive value (NPV), while PCT ≥1.7 had the highest specificity and positive predictive value (PPV). CRP ≥20 achieved the highest area under receiver operating characteristic curve (AUC) of 0.741 (95% confidence interval [CI] 0.672-0.810). The Step-by-Step (original) approach had the highest sensitivity (97.7%). Lab-score had the highest AUC of 0.695 (95% CI 0.621-0.768), compared to PECARN rule at 0.625 (95% CI 0.556-0.694) and Step-by-Step (original) at 0.573 (95% CI 0.502-0.644). In predicting IBIs, PCT ≥1.7 had the highest sensitivity, specificity, PPV and NPV. The Step-by-Step (original and modified) approach had the highest sensitivity of 100%. Lab-score had the highest AUC of 0.854 (95% CI 0.731-0.977) compared to PECARN rule at 0.589 (95% CI 0.420-0.758) and Step-by-Step at 0.562 (95% CI 0.392-0.732). CONCLUSION CRP strongly predicted SBIs, and PCT strongly predicted IBI. The Step-by-Step approach had the highest sensitivity and NPV, while Lab-score had the highest specificity and AUC in predicting SBIs and IBIs.
Infant ; Humans ; Child ; Calcitonin ; Prospective Studies ; Emergency Service, Hospital ; Bacterial Infections/diagnosis* ; Fever/diagnosis* ; C-Reactive Protein/analysis* ; Meningitis, Bacterial/diagnosis* ; Bacteremia ; Biomarkers ; Emergency Medical Services ; Procalcitonin

OBJECTIVES: Varicella-zoster virus (VZV) is one of the most common etiologies of viral meningitis/encephalitis. The early clinical manifestations and cerebrospinal fluid (CSF) changes of VZV meningitis/encephalitis lack specificity, and it is easy to be misdiagnosed as other viral encephalitides or tuberculous meningitis. This study aims to investigate whether the clinical characteristics, CSF analysis findings, and CSF cytokine levels could distinguish VZV meningitis/encephalitis from central nervous system (CNS) herpes simplex virus (HSV) and Mycobacterium tuberculosis (MTB) infections. METHODS: The medical records from 157 CNS infections, including 49 HSV (45 HSV-1, 4 HSV-2), 55 VZV, and 53 MTB infections between January 2018 and June 2021 in the Cytology Laboratory, Department of Neurology, Third Xiangya Hospital of Central South University were retrospectively reviewed. The data of 3 groups included demographic characteristics, laboratory results, radiographic findings, and outcomes. The levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) in the CSF of 68 patients (13 HSV, 22 VZV, and 33 MTB infection cases) were quantified. Clinical and laboratory data were compared among the 3 groups. RESULTS: The most common clinical manifestations in the 3 groups were fever, headache, vomiting, and neck stiffness. The clinical manifestations of HSV and VZV CNS disease were similar, although fever and altered consciousness were less common in the VZV group than those in the HSV and MTB groups (63.6% vs 87.8% vs 96.2%, P<0.001, and 14.5% vs 26.5% vs 47.2%, P=0.004, respectively). Seven patients (7/55, 12.7%) presented cutaneous zoster in the VZV group. CSF leukocyte count was significantly higher in the VZV group (230×10⁶ cells/mL) and MTB groups (276×10⁶ cells/mL) than that in the HSV group (87×10⁶ cells/mL, P=0.002). CSF protein level was significantly higher in the VZV than that in the HSV group (1 034 mg/L vs 694 mg/L, P=0.011) but lower than that in the MTB group (1 744 mg/L, P<0.001). IL-6 (VZV vs HSV vs MTB: 2 855.93 pg/mL vs 2 128.26 pg/mL vs 354.77 pg/mL, P=0.029) and IL-8 (VZV vs HSV vs MTB: 4 001.46 pg/mL vs 1 578.11 pg/mL vs 1 023.25 pg/mL, P=0.046) levels were significantly different among the 3 groups and were elevated in the VZV group.Post hoc analysis revealed that IL-6 and IL-8 were significantly higher in the VZV group than those in the MTB group (P=0.002 and P=0.035, respectively), but not in the HSV group (P>0.05). CONCLUSIONS VZV meningitis/encephalitis presents with CSF hypercellularity and proteinemia, challenging the classical view of CSF profiles in viral encephalitis. CSF IL-6 and IL-8 levels are elevated in patients with VZV meningitis/encephalitis, indicating a more intense inflammatory response in these patients.
Humans ; Central Nervous System Infections ; Encephalitis ; Encephalitis, Varicella Zoster/diagnosis* ; Encephalitis, Viral/diagnosis* ; Herpesvirus 3, Human ; Interleukin-6 ; Interleukin-8 ; Meningitis ; Retrospective Studies

Meningitis is a life-threatening disease. In order to reduce its threat to public health, the World Health Assembly indorsed a resolution in 2020 for urgent global action to prevent and control meningitis. Defeating Meningitis by 2030: a Global Roadmap was officially launched by the World Health Organization in 2021. We interpreted some key information of the roadmap from the aspects of coverage, objectives and pillar strategies, providing ideas for further strengthening the prevention and control of bacterial meningitis in China.
China/epidemiology* ; Global Health ; Humans ; Meningitis, Bacterial/prevention & control* ; World Health Organization

Objective: To explore the value of metagenomic next-generation sequencing (mNGS) in the etiology diagnosis of bacterial meningitis in children. Methods: The etiological results of 189 children diagnosed with "bacterial meningitis" or "purulent meningitis" or "central nervous system infection" in the Children's Hospital of Fudan University from 1st January 2019 to 31st December 2020 were analyzed retrospectively. The cerebrospinal fluid (CFS) of the children with bacterial meningitis was detected by culture and mNGS respectively, and the difference of pathogen detection rate between the 2 methods was analyzed. According to the age at the time of visit, the children were divided into neonatal group (≤28 days of age) and non-neonatal group (>28 days of age), and χ² test was used to compare the positive rate between the 2 groups. Taking CFS culture as the gold standard, the sensitivity and specificity of mNGS in the diagnosing of bacterial meningitis in children were analyzed. Results: Among these 189 children with bacterial meningitis, 116 were males and 73 were females. A total of 76 strains of pathogens were detected in blood and (or) CSF cultures, of which 50 strains (65.8%) were Gram-positive bacteria; among those, 18 strains (23.7%) of Streptococcus agalactiae, 17 strains (19.7%) of Escherichia coli and 15 strains (19.7%) of Streptococcus pneumoniae were detected with higher detection rate. The infection rate of Gram-positive bacteria in the non-neonatal group was higher than that in the neonatal group (76.0% (38/50) vs. 50.0% (13/26), χ²=5.24, P=0.020).The same CSF samples of 48 cases were tested by mNGS and culture at the same time, and the detection rate of mNGS was higher than that of CSF culture (20 cases (41.7%) vs. 12 cases (25.0%), χ²=16.45, P<0.001). The consistency of mNGS and culture results was 79.2% (38/48), and the same pathogen was detected in 11 children with both positive mNGS and CSF culture. Taking the results of CSF culture as the gold standard, the sensitivity of mNGS in the diagnosing of bacterial meningitis was 91.7%, and the specificity was 75.0%. Conclusions: The mNGS technology can improve the pathogen detection rate of bacterial meningitis in children, and has a high consistency with CSF culture. In suspected cases where the pathogen cannot be identified by traditional methods, CSF mNGS should be considered timely.
Child ; Escherichia coli ; Fatigue Syndrome, Chronic ; Female ; Gram-Positive Bacteria ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Meningitis, Bacterial/microbiology* ; Metagenomics/methods* ; Retrospective Studies ; Sensitivity and Specificity

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases