Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis

Scheld, W. Michael; Brodeur, James P.

doi:10.1128/aac.23.1.108

Cited by 38 publications

(11 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study demonstrates that the penetration of amikacin into the CSF is highly dependent on the degree of meningeal inflammation, as assessed by the degree of hypoglycorrhachia. This is consistent with findings for amikacin and other aminoglycosides in animal models of meningitis (18,19). Previous clinical studies found that aminoglycoside penetration of the blood-brain barrier was poor.…”

supporting

confidence: 81%

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Gaillard

Silly

Masne

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of <1, 1 to 2, and >2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is <1 mmol/liter on admission.

show abstract

supporting

confidence: 81%

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Gaillard

Silly

Masne

et al. 1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Although dexamethasone was administered to all patients and CSF vancomycin levels varied widely, we can not exclude the possibility that it had some importance in our vancomycin therapy failures by impairing BBB vancomycin penetration. In experimental models of meningitis, corticosteroids have been shown to reduce meningeal inflammation (22), permeability of the BBB (16), and peak CSF concentrations of multiple antimicrobial agents (25); dexamethasone has rarely been associated with human therapeutic failures (2). However, its recent usage as an early therapeutic adjunctive to cefuroxime or ceftriaxone in a high number of cases of bacterial meningitis in infants and children has not been associated with delayed sterilization of CSF or a significant rate of relapses (21).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

Viladrich

Gudiol

Liñares

et al. 1991

Antimicrob Agents Chemother

238

View full text Add to dashboard Cite

The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.

show abstract

“…The effects of methylprednisolone or dexamethasone on water content of the brain, CSF pressure, and lactate con- (132).…”

Section: Adjunctive Therapeutic Strategiesmentioning

confidence: 99%

Pathogenesis and pathophysiology of bacterial meningitis

1993

Self Cite

View full text Add to dashboard Cite

Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder.

show abstract

Effect of methylprednisolone on entry of ampicillin and gentamicin into cerebrospinal fluid in experimental pneumococcal and Escherichia coli meningitis

Cited by 38 publications

References 19 publications

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

Pathogenesis and pathophysiology of bacterial meningitis

Contact Info

Product

Resources

About