Correlation of Cerebrospinal Fluid Endotoxinlike Activity with Clinical and Laboratory Variables in Gram-negative Bacterial Meningitis in Children

Detection of endotoxinlike activity in cerebrospinal fluid by Limulus amebocyte lysate gelation has been suggested as a useful technique for the diagnosis of gram-negative bacterial meningitis. We prospectively screened 1,503 cerebrospinal fluid specimens with a Limulus amebocyte lysate microassay. The limit of sensitivity of the assay was 0.01 ng/ml. All specimens that were positive for endotoxinlike activity were subjected to confirmatory retesting, after which 38 (86%) remained positive. Comparison with available culture results revealed that 33 of 38 specimens (86%) were culture positive; 3 of the 5 culture-negative specimens were from patients on therapy for gram-negative bacterial meningitis, and 1 was from a neonate. The overall specificity of confirmed positive tests was 99.5%, with a positive predictive value of 97.3%. There was one false-negative specimen, giving an overall sensitivity of 97.3% and a negative predictive value of 99.9%. Endotoxinlike activities of greater than or equal to 150 ng/ml correlated with present illness of less than 2 days' duration (P = 0.024), elevated cerebrospinal fluid protein (P less than 0.05), and seizures (P = 0.004); levels of greater than or equal to 3,000 ng/ml correlated with neutropenia (P = 0.032), and levels of greater than or equal to 3.2 X 10(6) ng/ml correlated with death (P = 0.001). We conclude that the Limulus amebocyte lysate microslide gelation test has prognostic value as a sensitive, specific, simple, inexpensive screening test for gram-negative bacterial meningitis.