Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.
BACKGROUND
Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy.


METHODS
In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF).


RESULTS
Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01).


CONCLUSIONS
Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).
Ricard
Jean-Damien
JD
Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médicale, Colombes, 92700, France.
Wolff
Michel
M
Lacherade
Jean-Claude
JC
Mourvillier
Bruno
B
Hidri
Nadia
N
Barnaud
Guilène
G
Chevrel
Guillaume
G
Bouadma
Lila
L
Dreyfuss
Didier
D
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002439:Cefotaxime / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008875:Middle Aged; D014640:Vancomycin / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D014640:Vancomycin; D003907:Dexamethasone; D002439:Cefotaxime