A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults

Abstract

Third-generation cephalosporins are presently the agents of choice for the empirical antimicrobial therapy of bacterial meningitis. However, a number of factors associated with these agents, namely the development of resistance by pneumococci, limited activity against some Enterobacteriaceae and Pseudomonas spp., and the possible adverse effects of their bactenolytic mode of action, indicate that newer classes of antimicrobial agents be evaluated for the treatment of bacterial meningitis. Meropenem is a carbapenem antibiotic which is highly active against the major bacterial pathogens causing meningitis, and penetrates well into the cerebrospinal fluid. Two prospective randomised studies in 56 adult bacterial meningitis patients have compared meropenem 40 mg/kg 8-hourly, up to a maximum of 6 g/day (n = 28) with cephalo-sporin treatment, i.e. cefotaxime (n = 17) or ceftriaxone (n = 11). Patients were assessed by neurological examination, Glasgow Coma Score and Herson-Todd score. Clinical cure was observed in all 23 evaluable patients treated with meropenem (100%) and with 17 of the 22 evaluable cephalosporin-treated patients (77%). All pre-treatment isolates were eradicated except one isolate of Staphylococcus aureus in a cefotaxime-treated patient. Neurological sequelae were noted in three meropenem and four cephalosporin-treated patients. No patients in either treatment group experienced seizures after the start of therapy. This was despite the fact that a patient in each group had experienced seizures before therapy, several had underlying CNS disorders, and that doses of 6 g/day of meropenem were given. Hearing impairment was recorded in 11 meropenem and nine cephalosporin treated patients. Three patients in the meropenem group and one in the cephalosporin group died during treatment for reasons unrelated to study therapy. Overall, the results of this study indicate that meropenem is an effective and well-tolerated antibiotic for the treatment of bacterial meningitis in adults.