Influence of the blood bacterial load on the meningeal inflammatory response in Streptococcus pneumoniae meningitis

Abstract

Background: Despite bacteraemia is present in the majority of patients with pneumococcal, little is known about the influence of the systemic infection on the meningeal inflammatory response.

Methods: To explore the role of systemic infection on the meningeal inflammation, experimental meningitis was induced by intracisternal injection of approximately 1 x 10(6) CFU Streptococcus pneumoniae, type 3, and the 26 rabbits were either provided with approximately 1 x 10(6) CFU S. pneumoniae intravenously at 0 hour ("bacteraemic" rabbits, n = 9), immunized with paraformaldehyde-killed S. pneumoniae for 5 weeks prior to the experiment ("immunized" rabbits", n = 8), or not treated further ("control" rabbits, n = 9). WBC and bacterial concentrations were determined in CSF and blood every second hour during a 16 hours study period together with CSF IL-8 and protein levels. We also studied CSF and blood WBC levels in 153 pneumococcal meningitis patients with and without presence of bacteraemia.

Results: As designed, blood bacterial concentrations were significantly different among three experimental groups during the 16 hours study period (Kruskal Wallis test, P < 0.05), whereas no differences in CSF bacterial levels were observed (P > 0.05). Blood WBC decreased in bacteraemic rabbits between approximately 10-16 hours after the bacterial inoculation in contrast to an increase for both the immunized rabbits and controls (P < 0.05). The CSF pleocytosis was attenuated in bacteraemic rabbits as compared to the two other groups between 12-16 hours from time of infection (P < 0.017), despite accelerated CSF IL-8 levels in bacteraemic rabbits. In patients with pneumococcal meningitis, no significant difference in CSF WBC was observed between patients with or without bacteraemia at admission (n = 103, 1740 cells/microL (123-4032) vs. n = 50, 1961 cells/microL (673-5182), respectively, P = 0.18), but there was a significant correlation between CSF and blood WBC (n = 127, Spearman rho = 0.234, P = 0.008).

Conclusion: Our results suggest that a decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal meningitis results in an attenuated CSF pleocytosis.

Figure 1

CSF and blood bacterial concentration during experimental pneumococcal meningitis. *Significant difference between groups (Kruskal Wallis test, P < 0.05). There was a significant higher blood bacterial concentration in bacteraemic rabbits (n = 9) than in controls (n = 9) at 2–6 and 12 hours and than in immunized rabbits (n = 8) at 2–16 hours, respectively, and higher in controls than in immunized rabbits at 10–16 hours (Mann Whitney test, P < 0.017). All data are shown as medians (25–75 percentiles).

Figure 2

CSF and blood WBC concentration during experimental pneumococcal meningitis. *Significant difference between groups (Kruskal Wallis test, P < 0.05). Bacteraemic rabbits (n = 9) had significantly lower CSF WBC counts as compared to controls (n = 9) and to immunized rabbits (n = 8) between 12–16 hours (Mann Whitney test, P < 0.017). Bacteraemic rabbits had significantly lower blood WBC levels as compared to controls at 8 hours and between 12–16 hours and to immunized rabbits between 12–16 hours, respectively (Mann Whitney test,P < 0.017). All data are shown as medians (25–75 percentiles).

Figure 3

CSF IL-8 and protein concentration during experimental pneumococcal meningitis. All data are shown as medians (25–75 percentiles). *Significant difference between groups (Kruskal Wallis test, P < 0.05).

Figure 4

Correspondent CSF and blood WBC concentrations in patients with pneumococcal meningitis. Correlation between CSF and blood WBC: all patients (n = 127, rho = 0.234, P = 0.008), patients with a positive blood culture (n = 89, rho = 0.272, P = 0.01) and patients with a negative blood (n = 38, rho = 0.159, P = 0.34). No significant difference in CSF WBC between patients with a positive or a negative blood culture (P > 0.05).