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 bacteriolytic 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 cephalosporin 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.

Time-Kill Studies of Antimicrobial Combinations Including Cefotaxime, Ceftriaxone, Vancomycin and Meropenem against Cephalosporin-Resistant <i>Streptococcus pneumoniae</i>

“…Fuchs et al [28] reported that among 342 clinical isolates of S. pneumoniae, meropenem MICs for penicillin-resistant strains were 0.25-4.0 mg/l, while those of penicillin-susceptible strains were X0.008-0.06 mg/l. Meropenem has already been tested for the treatment of meningitis in both adults and children, but only a small amount of data for patients infected by penicillin-and cephalosporin-resistant S. pneumoniae is available to date [29][30][31]. More clinical data are required before it can be recommended as an effective antimicrobial agent for such cases.…”

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

“…Meropenem has been shown to be effective in several animal models [13]. In clinical trials, it has been used successfully to treat pneumonia [26,29], meningitis [11,21,37], intra-abdominal infections [16,17,20], soft tissue infections [22,30], bacteremia [29], and urinary tract infections [8,29].…”

Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients

“…Worth mentioning is that vancomycin use has become the focus of considerable attention in recent years due to the emergence of vancomycin-resistant enterococci (VRE) and the recent description of Staphylococcus aureus with intermediate resistance to vancomycin (VISA). Importantly, previous vancomycin therapy is a risk factor for the development of VRE infection [17,20,21]. In view of these concerns our observation that meropenem may be associated with a lesser use of vancomycin suggests that meropenem has advantages over ceftazidime in this setting.…”

“…Meropenem, unlike imipenem/cilastatin, is relatively stable to renal dehydropeptidase-I (DHP-I) and therefore does not need to be co-administered with a DHP-I inhibitor such as cilastatin. Meropenem may be a more acceptable alternative to imipenem/cilastatin because it has shown a low incidence of nausea and vomiting and is well tolerated by the central nervous system (CNS) [15,16,17], even in neutropenic patients [7,18].…”