Objective: To measure levels of defensin and lactoferrin in the CSF of children with bacterial meningitis.

Study design: Prospective descriptive study involving children undergoing lumbar puncture during evaluation for meningitis.

Methods: CSF concentrations of defensin and lactoferrin were determined using enzyme-linked immunosorbent assays on 14 children with bacterial meningitis and 20 control children found to have normal CSF during the evaluation for meningitis. Pertinent clinical and laboratory data were gathered on all children.

Results: CSF concentrations of both defensin and lactoferrin were markedly elevated in children with bacterial meningitis as compared to controls (p < 0.0001). Defensin levels in patients with bacterial meningitis ranged from 128 ng/ml to 99,430 ng/ml with a mean of 31,196 ng/ml(SD +/- 32,396) and a median of 22,188 ng/ml. No control subject had detectable levels of defensin in the CSF. Lactoferrin levels ranged from 184 ng/ml to 21,733 ng/ml with a mean of 9158 ng/ml (SD +/- 6770) and a median of 8649 ng/ml. Lactoferrin was undetectable in the CSF of 19 of 20 controls. A significant correlation was found between defensin levels in the CSF and the total leukocyte count in the CSF (rs =.65, p =.01). In addition, defensin levels correlated with the absolute neutrophil count in the CSF (rs =.66, p =.01). Lactoferrin levels in the CSF failed to correlate with either total leukocyte count or absolute neutophil count in the CSF (rs = -.12, p =.66 and rs =.04, p =.9 respectively). Neither defensin or lactoferrin levels in the CSF correlated with peripheral blood total leukocyte(rs =.15, p =.6 and rs =.01,p =.97 respectively) or absolute neutrophil counts(rs = -.13, p =.71 and rs =.08,p =.81 respectively).

Conclusions: Significant elevations of defensin and lactoferrin found in the CSF of children with bacterial meningitis are indicative of endogenous antimicrobial peptide and polypeptide release. We speculate elevations in defensin and lactoferrin may better reflect the intensity of the host response than traditional CSF studies. Defensin appears to parallel neutrophil activation more closely than does lactoferrin. Further investigation is warranted to determine the utility of these antimicrobial molecules as a diagnostic tool and therapeutic monitor in the evaluation of children with bacterial meningitis. Rapid bedside assays for both molecules are being developed and we are currently quantifying these antimicrobial molecules in aseptic meningitis.