Cerebrospinal Fluid In Bacterial Meningitis Research Articles

Impact of COVID-19 on the Prevalence and Drug Resistance of Bacteria Isolated From Bacterial Meningitis Cerebrospinal Fluid in Shandong Province: A Multicenter Retrospective Study.

Our objective was to evaluate the ramifications of the 2019 coronavirus disease (COVID-19) pandemic on the microbial profile and antimicrobial resistance patterns of bacteria isolated from cerebrospinal fluid (CSF) specimens of patients with bacterial meningitis. We conducted a retrospective analysis of laboratory results and clinical records about positive CSF cultures reported by the SPARSS network from 2017 to 2023. The study covered three distinct periods: January 2017 to December 2019 (before the COVID-19 pandemic), January 2020 to December 2022 (during the COVID-19 pandemic), and January 2023 to December 2023 (after the COVID-19 pandemic), with a total of 5793 CSF isolates collected. Notably, the proportion of male patients (61.3%) was higher than that of females. After COVID-19, we observed a notable shift in the seasonal peak of CSF pathogens, with a delay of approximately 3 months. Remarkable alterations were evident in both pediatric and adult CSF isolate profiles. In children, the predominant pathogens included coagulase-negative Staphylococcus (CoNS), Streptococcus pneumonia, and Escherichia coli. Notably. After COVID-19, there was a significant decrease in the proportion of CoNS (p = 0.0039) and a notable increase in E. coli (p = 0.0067). In adults, the top three pathogens were CoNS, Acinetobacter baumannii, and Klebsiella pneumoniae. After the pandemic, we observed a significant reduction in the prevalence of A. baumannii (p = 0.0059), while the proportions of K. pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis increased significantly (p < 0.05). Additionally, among multidrug-resistant bacteria, the detection rate of carbapenem-resistant E. coli escalated (p = 0.0375). Antimicrobial susceptibility analysis indicated a declining trend in resistance rates for CoNS and A. baumannii to certain antibiotics following the pandemic. Conversely, resistance to imipenem in A. baumannii increased. In conclusion, the COVID-19 pandemic has significantly influenced the composition, antimicrobial resistance patterns, and epidemiological dynamics of CSF-isolated bacteria in Shandong province. To effectively address these changes, ongoing and dynamic surveillance of pathogen trends and antimicrobial resistance rate is essential.

Enhancing the cytological features and diagnostic significance of cerebrospinal fluid in bacterial meningitis.

The objective of this study was to investigate the cytological features and diagnostic significance of cerebrospinal fluid (CSF) in bacterial meningitis (BM). Patients diagnosed with BM at the First Affiliated Hospital of Nanchang University Hospital between August 2021 and April 2022 were enrolled. Clinical, cranial imaging, CSF-next-generation sequencing, CSF examination, and CSF cytology data were retrospectively analyzed. CSF cytology samples were prepared using a CSF cell pelletizer (precipitation method) and stained using the May-Grunwald-Glemsa (MGG) method. The χ2 test was employed to compare the positive rate of routine CSF count and CSF cytology. Eight patients (four males and four females), aged 41-67 years, were included. Among them, two patients had undergone brain surgery within the past 4 months, one patient had an 8-year history of otitis media, and two patients had a history of sudden toothache. Clinical manifestations included fever, headache, sudden disturbance of consciousness, and neck stiffness. CSF cytology revealed abnormal inflammatory changes dominated by neutrophils in seven patients. Routine CSF cell counts exceeded 100/uL in only four cases, indicating a higher positive rate of CSF cytology for detecting CSF inflammatory reactions compared to routine cell count. Comparative detection of bacteria through the observation of CSF cytology inflammatory status in BM patients are more useful for diagnosing BM than routine CSF counts.

Pathological and Microbiological Analysis of Cerebrospinal Fluid in Bacterial Meningitis

Background: Meningitis is a life threatening infection with incidences increasing in adults and children. CSF analysis is a key tool to diagnose and differentiate between bacterial, viral, tubercular and fungal meningitis. Identifying the causative bacterial organisms is important to guide antimicrobial therapy. Aims & objectives: The present study was undertaken to analyze CSF parameters and to determine causative organisms of meningeal infection and also to find out their antibiotic susceptibility pattern. Settings and design: Cross sectional study. Methods and Materials: The study includes 100 clinically suspected cases of meningitis. Pathological and Biochemical analysis was done. Bacterial pathogens were identified by conventional methods of culture with sensitivity pattern. Results: Out of 100 cases, 30 cases showed total count >1000cells/ul with neutrophil predominance. 25 cases shows culture growth, with Escherichia coli as predominant organism isolated followed by Streptococcus pneumonia. Imipenem showed 100% sensitivity followed by Pipercillin/Tazobactum 90%. Conclusion: Our results of CSF fluid analysis revealed a total count of >1000 cells /ul with neutrophil predominance. Escherichia coli was the predominant organism isolated. Imipenem showed 100% sensitivity.

Study on the correlation between insulin-like growth factor-I and neuron-specific enolase in cerebrospinal fluid of children with CNS infection

Objective To explore the correlation between insulin-like growth factor-I （IGF-I） and neuron-specific enolase （NSE） in cerebrospinal fluid （CSF） of children with CNS infection. Methods 90 cases were recruited in the study, among which 30 cases were patients with bacterial, meningitis （BM）, 30 cases with viral encephalitis （VM） and the rest belonged to contrast groups. CSF of all 90 cases was collected during the period from 24 to 48 hours after admission. IGF-I and NSE in CSF were measured by FJ-2008 PS γ immunocount instrument. Results Both BM and VM group had a significant difference in IGF-I and NSE as compared with control group （P 〈 0.01）, but there was no significant difference between BM and VM group （P〉0.05）. IGF-I and NSE in CSF of BM and VM group were not correlated with each other. However, IGF-I and NSE showed positive correlation in 15 patients with conscious disturbance （r = 0.94, P 〈 0.01）. Conclusion Our study showed that IGF-I and NSE in CSF of patients with CNS infection increased greatly. IGF-I and NSE in CSF of critically ill children were correlated positively. It suggests that IGF-I play a certain role in protecting and repairing central nervous system. Key words: Central nervous system; Infection; Cerebrospinal fluid; Insulin-like growth factor-I; Neuron-specific enolase

Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells.

Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-gamma, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-gamma on moDC. moDC cultured with MS CSF induced a higher production of IFN-gamma from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.

Increased Activity of Lysosomal Enzymes in the Peritoneal Fluid of Bacterial Peritonitis

The activity of lysosomal enzymes is increased in the cerebrospinal fluid of bacterial meningitis, suggesting that inflammation may cause leakage of lysosomal enzymes into the extracellular fluid. Our objective was to study the activity of 3 lysosomal enzymes in cell-free peritoneal fluid of patients with peritoneal inflammation. The beta-galactosidase, beta-glucuronidase, and alpha-mannosidase activity (nmol 4-methylumbelliferone/mL/h); the total, polymorphonuclear, and mononuclear cell number; and chemical parameters were determined in the peritoneal fluid of 26 patients with culture-positive acute bacterial peritonitis, 13 patients (under antibiotic treatment) with culture-negative bacterial peritonitis, 6 patients with acute mesenteric lymphadenitis, and 26 control subjects who were operated on for surgical conditions without peritoneal inflammation. The median beta-galactosidase activity in the culture-positive bacterial peritonitis, mesenteric lymphadenitis, and controls was 175 (range: 63--2210), 50 (range: 37--56), and 16 (range: 8--32), respectively. The beta-glucuronidase was 488 (range: 79--998), 53 (range: 27--98), and 15 (range: 3--22), respectively. The alpha-mannosidase was 801 (range: 100-3172), 78 (range: 33--157), and 41 (range: 16--63), respectively. The differences of the enzyme activities among the groups of the subjects studied were significant, with the exception of the alpha-mannosidase activity between mesenteric lymphadenitis and controls. There was no significant correlation between the enzyme activities and the cytologic or chemical parameters studied. The elevation of the lysosomal enzymes' activity in the peritoneal fluid of patients with bacterial peritonitis seems to be a reliable index of peritoneal infection. Of the enzymes studied, the beta-glucuronidase and beta-galactosidase activities provide the best means for diagnosing bacterial inflammation of the peritoneal cavity.

C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro.

The appearance of polymorphonuclear and mononuclear leukocytes in the cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis. Chemokines are candidate mediators of cell migration from blood into the subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the csf of patients with pyogenic meningitis were measured by ELISA. Highly significant elevations of chemokine levels in comparison with noninflammatory csf controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth-related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to 18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES (regulated upon activation, normal T cell expressed and secreted). The csf of bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes. Correlation analysis demonstrated a strong association between individual chemokine levels and chemotactic activity mediated by csf. A significant reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth-related gene product alpha Abs, and a reduction of mononuclear cell migration was achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1 alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found between csf leukocyte counts and chemokine concentrations or chemotactic activity mediated by csf, additional factors influence the extent of pleocytosis in vivo.

Increased activity of lysosomal acid hydrolases in the cell-free cerebrospinal fluid of bacterial meningitis.

Because inflammation could affect lysosomal enzyme trafficking, resulting in increased enzyme release from the cells, tissue necrosis, or altered blood- and the brain-cerebrospinal fluid (CSF) barrier, the activity of four lysosomal enzymes in the cell-free CSF of 34 patients with bacterial meningitis, 20 with aseptic meningitis, and 39 control subjects was measured. Activities are expressed in nanomoles of 4-methylumbelliferone mL/h. The median beta-hexosaminidase A activity in bacterial meningitis was 313, in aseptic meningitis it was 173, and in the control subjects it was 175, the median beta-hexosaminidase B activity was 417, 165, and 120; the median alpha-mannosidase activity was 171, 124, and 113; and the median beta-glucuronidase activity was 133.7, 14.3, and 10.0, respectively. The difference of the activities of the four enzymes measured between the bacteria meningitis and the controls is significant (p < 0.000). Also significant is the difference between bacterial and aseptic meningitis (p = 0.005 to < 0.000), but it is not significant between aseptic and control subjects. Both the sensitivity and specificity of the beta-glucuronidase activity between bacterial meningitis and control subjects were 100%, whereas the corresponding values between bacterial and aseptic meningitis were 100% and 90%, respectively. No significant correlation was observed between the activities of the enzymes measured and the number of the polymorphonuclear leukocytes or other laboratory characteristics of the CSF. The increased lysosomal enzyme activities in the CSF of patients with meningitis may result from diffusion across the blood-CSF or the brain-CSF barrier or from enzyme leakage through the cell membranes.

Excess glutamate in the cerebrospinal fluid in bacterial meningitis

We investigated possible neurotoxic components in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. On murine cerebellar neuronal cell cultures, CSF exerted a dose-dependent toxic effect, which was attenuated by the NMDA receptor antagonist MK-801. Glutamate concentrations in the CSF of patients with bacterial meningitis were measured by an enzymatic assay and found to be significantly elevated (p < 0.001) as compared to viral meningitis and non-inflammatory neurological diseases. The concentration of glutamate in the CSF of patients with bacterial meningitis varied considerably and correlated with the severity of the disease as scored by the Glasgow Coma Scale. Cells in the CSF, mainly comprising polymorphonuclear granulocytes, did not release any glutamate into the culture medium, whereas blood monocytes produced remarkable amounts. These findings implicate an important role of monocytic inflammatory cells in bacterial meningitis by the release of glutamate, which may contribute to neuronal cell death.

Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-α and IL-1α and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.

Absence of intrathecal synthesis of some interferon-alpha subtypes in bacterial meningitis.

Sixty-five cerebrospinal fluid (CSF) samples from 54 infants and children with bacterial meningitis were analyzed for the presence of interferon (IFN)-alpha with a biologic assay. Of the 65 samples, 3 were positive (2-4 IU/mL) and only 1 of 56 collected early was at 4 IU/mL. These results suggest that some subtypes of IFN-alpha already reported as present in viral infections of the central nervous system are not detected in bacterial meningitis by our IFN assay. This difference may be helpful in differentiating bacterial from viral infections and also in evaluating the quality of the virologic investigation; moreover, the rarity of IFN-gamma in CSF in bacterial meningitis needs further investigation to understand its role in the pathogenesis of the disease.

α2-macroglobulin and C-reactive protein in cerebrospinal fluid in bacterial meningitis

α2-macroglobulin and C-reactive protein in cerebrospinal fluid in bacterial meningitis

β-Lactamase-producing Branhamella catarrhalis causingotitis media in children

additional 24% are sensitive to the initial therapy, and the majority (57%) have bacteriologically negative middle-ear fluid. Clinical failure in the group without antimicrobial resistance is unexplained. The antimicrobial sensitivity of a given bacterial species is determined in vitro with a fixed inoculum of bacteria, usually in the range of 104 to 105 CFU/ml. If the inoculum exceeds 105 , the concentration of antibiotic required to inhibit the growth of the organism may increase considerably for common bacterial pathogens such as H. influenzae ~ and B. catarrhalis, 2 particularly if they are betalactamase producers. Colony counts in infected body fluids vary considerably. The cerebrospinal fluid in bacterial meningitis commonly has a concentration of bacteria that exceeds 106 and may even reach 108 CFU/ml; the density of bacteremias is usually < l03 CFU/ml. 4-6 In our study the concentration of bacteria in middle-ear fluid of patients with acute otitis media frequently exceeded 104 and occasionally 105 CFU/ ml. As expected, the Gram stain of middle ear fluid was positive in most instances when the colony count exceeded 104 CFU/ml. This observation is consistent with the fact that bacteria in a variety of body fluids (e.g., unspun urine, blood, and cerebrospinal fluid) are not usually easily detected unless they are present in concentrations approximately 105 CFU/ml? The absence of a more perfect correlation between the findings on Gram stain and colony count may be related to the quality of the middle-ear fluid. The volume delivered by a calibrated loop may be less reproducible when the fluid is thick and viscous. In patients with acute otitis media, clinical failures and persistent or recurrent effusions are poorly understood, particularly when tympanocentesis yields antibiotic-sensitive microorganisms. Noncompliance with orally administered antimicrobial regimens or inadequate duration of therapy may explain some instances of clinical failure. It could be speculated that initially high bacterial colony counts may be one of the factors determining outcome in the treatment of acute otitis media. We thank Helen Schorner for secretarial assistance.