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Updated: Apr 11, 2026
Real-Time Quantification of Reactive Oxygen Species in Neutrophils Infected with Meningitic Escherichia Coli
Published on: April 20, 2021
Multicenter testing of the rapid quantification of radical oxygen species in cerebrospinal fluid to diagnose
Anne-Claire Lukaszewicz1, Valérie Faivre1, Hélène Bout2
1Department of Anesthesiology and Critical Care, Lariboisière Hospital, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.
Purpose:
Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in febrile patients several days after trauma or surgery.
Methods:
Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts.
Results:
The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) [0.684-0.820]) for steady-state and 0.818 (95% CI [0.655-0.821]) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively.
Conclusion:
The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis.
Insights
Reactive oxygen species (ROS) in cerebrospinal fluid (CSF) can help diagnose meningitis after traumatic brain injury (TBI) or neurosurgery. Elevated ROS levels in CSF effectively rule out bacterial meningitis in febrile patients.
Area of Science:
- Neurology
- Infectious Diseases
- Biochemistry
Background:
- Meningitis is a critical complication following traumatic brain injury (TBI) and neurosurgery.
- Early and accurate diagnosis of meningitis is essential for timely treatment and improved patient outcomes.
Purpose of the Study:
- To evaluate the diagnostic utility of reactive oxygen species (ROS) levels in cerebrospinal fluid (CSF) for identifying meningitis in febrile patients post-TBI or neurosurgery.
- To compare the performance of ROS testing with established CSF diagnostic criteria.
Main Methods:
- Prospective study involving febrile patients (>38°C) after TBI or neurosurgery.
- Measurement of ROS in CSF via luminescence, both in basal state and after phorbol 12-myristate 13-acetate (PMA) stimulation.
- Validation in two cohorts: a single-center training cohort (n=54) and a multicenter testing cohort (n=136).
Main Results:
- Significantly higher ROS production in CSF of meningitis patients compared to non-infected controls.
- ROS testing demonstrated good diagnostic performance, with Area Under the Curve (AUC) values around 0.81 in the training cohort.
- High negative predictive values and low negative likelihood ratios were observed in the testing cohort, particularly after PMA stimulation.
Conclusions:
- Cerebrospinal fluid ROS testing is a promising tool for ruling out bacterial meningitis.
- This assay can aid clinicians in excluding meningitis in febrile patients with a history of TBI or neurosurgery.
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