Treatment of Bacterial Meningitis with Vancomycin
Ricard JD, Wolff M, Lacherade JC, et al. Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study. Clin Infect Dis. 2007 Jan 15;44(2):250-255. Epub 2006 Dec 15.
In 2002, van de Beek and de Gans published a study demonstrating that adjuvant dexamethasone decreased mortality and improved neurological disability when given to patients with bacterial meningitis. Their results changed our treatment paradigm for this disease but left us with several questions. At what point in the treatment course does giving corticosteroids become ineffective? Do their results apply to all bacterial pathogens? Can the results be applied to the use of vancomycin in treating penicillin-resistant strains of Streptococcus pneumoniae? This final question arises from the disturbing ability of vancomycin to penetrate the cerebrospinal fluid (CSF). Previous data support this concern; thus, bactericidal titers may be inadequate within the CSF. Because meningeal inflammation exerts a strong influence over whether or not vancomycin enters the CSF, administering steroids may decrease its ability to do so. This study brings some clarity to the issue.
In this observational open multicenter trial from France, 14 adults were admitted to intensive care units with suspected pneumococcal meningitis. They were treated with intravenous cefotaxime, vancomycin, and dexamethasone. The vancomycin was given as a loading dose of 15 mg per kg of body weight followed by administration of a continuous infusion of 60 mg per kg of body weight per day. The diagnosis of pneumococcal meningitis was made using a CSF pleocytosis as well as one or more of the following: a positive culture from either the blood or CSF, a Gram stain showing Gram-positive diplococci, or pneumococcal antigens in the CSF as demonstrated by latex agglutination. Patients had a second lumbar puncture on either day two or three to measure vancomycin levels—among other markers of disease activity—in the CSF. Serum levels of vancomycin were drawn simultaneously.
Thirteen of the 14 patients had pneumococcal meningitis; one patient was found to have meningitis from Neisseria meningitidis. Seven patients had pneumococcal strains resistant to penicillin. Ten of the 14 patients required mechanical intubation. The second lumbar puncture demonstrated marked improvements in leukocyte counts, protein levels, and glucose levels. All subsequent cultures from the CSF were negative. Three patients died, two had neurological sequelae, and the remainder were discharged from the hospital without complications. Vancomycin concentrations in the serum ranged from 14.2 to 39.0 mg/L, with a mean of 25.2 mg/L; concentrations in the CSF ranged from 3.1 to 22.3 mg/L, with a mean of 7.9 mg/L. There was a significant correlation between vancomycin levels in the serum and those in the CSF (r = 0.68; P = 0.01). The concentration of vancomycin in the CSF was between four and 10 times the mean inhibitory concentrations (MICs). A linear correlation exists between penetration of vancomycin into CSF and serum levels. No evidence of drug toxicities was observed.
The results demonstrate that a therapeutic concentration of vancomycin can be achieved in the CSF. The continuous infusion of vancomycin with a loading dose, which has not been standard practice, has previously been shown to achieve targeted serum levels more quickly than intermittent dosing. Levels of serum vancomycin were likely higher in this study than when troughs of 15-20 mg/L are the goal. This data strongly suggests, however, that this same treatment regimen can obtain adequate vancomycin levels in the CSF while treating pneumococcal meningitis with adjunctive steroids.