Vol.57 No.S-1 March 2009
Mechanism for tebipenem antimicrobial activity against Streptococcus pneumoniae and Haemophilus influenzae
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka, Kohoku-ku, Yokohama, Kanagawa, Japan
Abstract
Tebipenem(TBPM), an active form of the oral carbapenem tebipenem pivoxil, showed strong antibacterial activity against Streptococcus pneumoniae, and inhibited the growth of all S. pneumoniae strains including penicillin-resistant strains with altered penicillin-binding protein gene (pbp1a, pbp2x and pbp2b) at 0.12 μg/mL or less. TBPM showed higher binding affinity even for mutated PBP1A, PBP2X and PBP2B of S. pneumoniae than cefditoren(CDTR), faropenem(FRPM) or amoxicillin(AMPC). In vitro activity of TBPM against Haemophilus influenzae, including β-lactamase-nonproducing ampicillin-resistant strains with altered ftsI gene encoding PBP3, was stronger than that of FRPM or AMPC, and such activity was not so much affected by additional substitutions of amino acid. TBPM showed the high binding affinity for PBPs of H. influenzae ATCC49766. Frequencies of single-step mutation of S. pneumoniae and H. influenzae caused by TBPM were from 1.7×10-5 to <1.8×10-9 at 1 to 2 times the MIC. As in the case of other β-lactam antibiotics, TBPM prevented the emergence of resistant S. pneumoniae and H. influenzae strains at 4 times the MIC or less (0.008 to 0.12 μg/mL and 0.5 to 2 μg/mL, respectively). The susceptibilities of S. pneumoniae and H. influenzae to TBPM, CDTR or FRPM were decreased by 1/2-1/4 after 14-time repeated subcultures in the presence of TBPM, CDTR or FRPM, respectively, at sub-MIC, whereas that to levofloxacin (LVFX) was decreased by 1/2-1/32 in the presence of LVFX.
Key word
tebipenem, Streptococcus pneumoniae, Haemophilus influenzae, PBPs
Received
October 28, 2008
Accepted
February 6, 2009
Jpn. J. Chemother. 57 (S-1): 15-29, 2009
