Cerebrospinal fluid endotoxin levels in children with H. influenzae meningitis before and after administration of intravenous ceftriaxone

Bacterial meningitis due to Hemophilus influenzae remains a serious, frequently fatal disease. There has not been a significant reduction in case fatality rates, despite the availability of new and more potent antibiotics or chemotherapeutics. This adverse reaction may be due to the interaction between host cells and substances released when antibiotics destroy the bacteria. These products appear to stimulate pathophysiologic changes in the central nervous system (CNS), which can lead to irreversible injury to tissues in the system and produce long-term complications. Gram-negative organisms have high endotoxin (lipopolysaccharide, or LPS) concentrations in the outer membrane of the cell. Some antibiotic activity produces significant alterations in LPS levels in CNS fluids. A rise in LPS has been correlated with increased CNS injury. Ceftriaxone therapy resulted in a marked increase in free LPS in the cerebrospinal fluid of patients being treated for Hemophilus influenzae meningitis. This elevated LPS level correlated with increased CNS injury resulting in seizures, brain edema (swelling), and increased inflammation of the subarachnoid space (under the membrane surrounding the brain). The data reported here emphasize the need to evaluate therapy in which the antibacterial action causes the release of cellular products and components, which frequently are as toxic as the action of the intact bacterial cells. (Consumer Summary produced by Reliance Medical Information, Inc.)