CEFOTAXIME IN THE TREATMENT OF BACTERIAL MENINGITIS

We evaluated the efficacy of cefotaxime in the treatment of bacterial meningitis and the diffusion of the drug into CSF. Eleven children(9 days to 5 yrs) with meningitis due to H. influenzae (7 cases), S. pneumoniae(2) , group B streptococcus (1) , and Salmonella sp.(1), were treated with 40 mg/kg of IV cefotaxime q6hrs. Cefotaxime levels were determined by HPLC. The mean cefotaxime plasma level 3 hrs after a dose early in the treatment was 14.1 mg/L(range 5.1-42.2 mg/L), and the mean CSF level was 3.9 mg/L(0.7-16.6 mg/L). The mean CSF diffusion rate was 26.4%. At the end of treatment, the mean plasma level was 7.9 mg/L(1.5-13.6 mg/L) and the mean CSF level was 1.23 mg/L(0.5-3.1 mg/L) representing a mean diffusion rate of 21.9%. Cefotaxime MBC for the infecting organisms ranged between 0.015 mg/L and 0.25 mg/L. CSF was bactericidal to the infecting organisms at dilutions between 8 and 256. The CSF diffusion correlated positively with the cefotaxime plasma level (r=0.86), CSF protein (r=0.63), CSF leukocyte count (r=0.61) and negatively with CSF sugar (r=-0.37).All patients responded well to treatment with no apparent sequelae. Serial levels were also determined in 5 infants with ventriculostomies. Following a single dose of 40 mg/kg, the mean cefotaxime CSF levels (and mean plasma levels) were 6.6 mg/L(28.4 mg/L) at 2 hrs, 5.7 mg/L(8.9 mg/L) at 4 hrs, and 4.5 mg/L (1.8 mg/L) at 6 hrs. Cefotaxime diffuses sufficiently and consistently into CSF. Further assessment of its efficacy in the treatment of childhood meningitis is warranted.