The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis

Article Abstract:

Children who recover from bacterial meningitis often suffer permanent brain damage, which can express itself as loss of hearing, or neurological symptoms including paralysis and hydrocephalus. Much of this damage seems to result not from the bacterial infection of the meninges that cover the brain, but from the inflammation of the meninges that occurs as a part of the body's response to the infection. There have been some experimental studies to suggest that the corticosteroid drug dexamethasone may reduce the likelihood of permanent damage by reducing the inflammatory response. This has now been confirmed in a study involving 101 infants and children with meningitis. All the children were treated with the antibiotic drug cefotaxime to destroy the bacteria causing the meningitis. Fifty-two children also received dexamethasone treatment, while 49 received only a placebo drug in addition to the cefotaxime. As soon as 12 hours after the initiation of treatment, differences could be seen between the two groups. The pressure of the cerebrospinal fluid had already begun to drop in the corticosteroid-treated patients, while the pressure increased in the patients who received only antibiotic and placebo. Likewise, tumor necrosis factor alpha and platelet-activating factor were both reduced in the cerebrospinal fluid of the patients receiving the dexamethasone; these two substances are considered to play important roles in the inflammatory process. After a follow-up period averaging 15 months, permanent brain damage was more common among the patients who did not receive the dexamethasone. Seven of the 51 surviving children treated with dexamethasone suffered at least one symptom of permanent damage. In contrast, neurologic symptoms or hearing loss persisted in 18 of the 48 patients who survived after treatment with antibiotics only. These results add to the mounting body of evidence indicating that the corticosteroid treatment of the inflammatory response is a very important aspect of the treatment of meningitis in children. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prevention, Corticosteroids, Adrenocortical hormones, Neurologic manifestations of general diseases, Neurologic manifestations

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Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis

Article Abstract:

Meningitis (inflammation of the membranes that surround the brain) can be caused by several organisms, including Haemophilus influenzae type B. This bacterium, like all Gram-negative bacteria, is surrounded by an outer membrane containing lipopolysaccharides (LPS) or endotoxins: when these substances contact host tissue, they initiate a powerful inflammatory response that includes inflammation, brain swelling, increased pressure within the skull, and other changes. Haemophilus influenzae type B LPS have certain unique structural properties that may affect results when they are evaluated quantitatively using a standard assay (the Limulus amebocyte lysate assay). This study of endotoxin levels in patients with Haemophilus influenzae type B meningitis was carried out using lipo-oligosaccharide (LOS) instead of LPS as a standard. The patients were 38 children (aged between six weeks and 13 years) with Haemophilus influenzae type B bacteria in their cerebrospinal fluid. The children underwent treatment with cefotaxime sodium and dexamethasone sodium phosphate; the clinical severity of their conditions was monitored daily in the hospital. Results showed a steep drop in LOS levels between the time of admission to the hospital and 17 to 48 hours after therapy started. In general, the concentrations of Haemophilus influenzae type B in CSF predicted the likelihood of complications: patients who developed neurologic abnormalities had high LOS concentrations in the first CSF sample analyzed. LOS levels were also correlated with the levels of interleukin 1B (a factor released by cells of the immune system), protein, and glucose in CSF, as well as with the duration of secondary fever (a temperature of 38.0 degrees Centigrade or higher occurring after a fever-free period). The findings indicate that the level of endotoxin, as determined by the test described, in the CSF of patients with Haemophilus influenzae type B meningitis can be an important prognostic factor. (Consumer Summary produced by Reliance Medical Information, Inc.)

Diagnosis, Complications and side effects, Endotoxins, Hemophilus meningitis

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Cerebrospinal fluid prostaglandins, interleukin 1-beta, and tumor necrosis factor in bacterial meningitis: clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients

Article Abstract:

The death rate among children suffering from bacterial meningitis (infections of the membranes surrounding their brain and spinal cord) ranges from two to five percent. In approximately 20 percent of meningitis cases, the children are left with various neurologic problems. Recent advances in drug manufacture have provided newer and more powerful antimicrobial drugs for the treatment of meningitis, but the outcomes of treatment have not correspondingly improved. Some research has suggested that the endotoxins, or biologic poisons, produced by bacteria also induce the release of molecules by the body to mediate the inflammation of the meninges that characterizes the disease. These include prostaglandins, interleukins and tumor necrosis factor. Other animal experiments have shown that when some of these agents are injected into uninfected animals, injuries to the meninges and brain similar to those produced by bacterial meningitis occur. The levels of these chemical products were measured within the cerebrospinal fluid of patients with bacterial meningitis, before and after treatment with either dexamethasone (a synthetic glucocorticoid, used to control inflammation) or a placebo (an inactive control substance). In addition all patients also received various antibiotic treatments to sterilize their cerebrospinal fluid. Various prostaglandins, interleukins and tumor necrosis factor are found in the cerebrospinal fluid of most bacterial meningitis patients. Treatment for 18 to 30 hours with dexamethasone was found to lower prostaglandins and specific interleukins. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Prostaglandins, Tumor necrosis factor, Interleukin-1, Cerebrospinal fluid

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