Cerebrospinal fluid bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in children with meningitis treated with high-dosage cefotaxime.
We determined cefotaxime and desacetyl-cefotaxime concentrations in children with bacterial meningitis receiving high-dose cefotaxime (300 mg/kg of body weight/day) and concomitant dexamethasone therapy. The median peak cerebrospinal fluid cefotaxime and desacetyl-cefotaxime concentrations were 4.7 and 8.1 microg/ml, respectively. In vitro bactericidal activity (>99.9% killing in 6 h) was found in 17 (94%), 13 (72%), and 8 (44%) of 18 cerebrospinal fluid specimens against cefotaxime-susceptible, -intermediate (MIC, 1 microg/ml), and -resistant (MIC, 4 microg/ml) strains, respectively. High-dose cefotaxime, while safe, is not reliably sufficient therapy for cephalosporin-nonsusceptible pneumococcal meningitis, and combination therapy is recommended.
Friedland
I R
IR
Department of Pediatrics, Baragwanath Hospital, and The University of Witwatersrand, Johannesburg, South Africa. ifried@mednet.swmed.edu
Klugman
K P
KP
D002439:Cefotaxime / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use*; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D011008:Pneumococcal Infections; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D002511:Cephalosporins; C029281:desacetylcefotaxime; D002439:Cefotaxime