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Correlation of cerebrospinal fluid endotoxinlike activity with clinical and laboratory variables in gram-negative
Abstract:
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.
Insights
The Limulus amebocyte lysate (LAL) assay is a sensitive and specific screening tool for diagnosing gram-negative bacterial meningitis. This cost-effective test offers prognostic value, aiding in patient management and predicting outcomes.
Area of Science:
- Microbiology
- Clinical Diagnostics
- Biochemistry
Background:
- Gram-negative bacterial meningitis diagnosis relies on sensitive and specific methods.
- Limulus amebocyte lysate (LAL) gelation assay shows promise for detecting endotoxinlike activity in cerebrospinal fluid (CSF).
Purpose of the Study:
- To evaluate the diagnostic accuracy and prognostic value of the LAL microassay for gram-negative bacterial meningitis.
Main Methods:
- Prospective screening of 1,503 CSF specimens using a Limulus amebocyte lysate microassay.
- Confirmatory retesting of positive specimens and comparison with bacterial culture results.
- Analysis of correlations between endotoxinlike activity levels and clinical parameters.
Main Results:
- The LAL assay demonstrated high sensitivity (97.3%) and specificity (99.5%) for detecting gram-negative bacterial meningitis.
- Confirmed positive tests showed a positive predictive value of 97.3% and a negative predictive value of 99.9%.
- Higher endotoxinlike activity levels correlated with shorter illness duration, elevated CSF protein, seizures, neutropenia, and mortality.
Conclusions:
- The Limulus amebocyte lysate microslide gelation test is a sensitive, specific, simple, and inexpensive screening test for gram-negative bacterial meningitis.
- The LAL assay possesses prognostic value, correlating with disease severity and patient outcomes.