Activities of ertapenem, a new long-acting carbapenem, against penicillin-sensitive or -resistant pneumococci in experimental meningitis

Abstract

The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively. Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 +/- 0.17 and 0.59 +/- 0.22 log(10) CFU/ml x h, respectively, in the viable cell counts in the cerebrospinal fluid. The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain). In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains. Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro.

FIG. 1.

(A) Ertapenem concentrations in CSF for 8 h after one intravenous injection of 60 mg of ertapenem/kg. The concentrations of ertapenem in CSF remained above the MIC during the entire treatment period (MICs, 0.06 and 0.5 mg/liter for the penicillin-sensitive and -resistant strains, respectively). (B) Ertapenem concentrations in serum of rabbits after one injection of 60 mg/kg and in serum of human adults after one injection of 500 mg (MSD, personal communication [∗]).

FIG. 2.

Goodness-of-fit plots of the three-compartment PK model for ertapenem. The upper panels show measured serum concentrations (CONC) versus population and individual predictions (PRED and IPRED, respectively). The lower panels show measured CSF concentrations versus PRED and IPRED. Each solid line in the left panels represents one animal. Fine dashed lines are the lines of identity. The heavy dashed line represents the smoothness of measured concentrations versus PRED and IPRED, respectively.