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Antimicrobial Agents and Chemotherapy, March 2005, p. 889-894, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.889-894.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In Vitro Activity of Tebipenem, a New Oral Carbapenem Antibiotic, against Penicillin-Nonsusceptible Streptococcus pneumoniae

Laboratory of Infectious Agents Surveillance, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Shirokane, Minato-ku,¹ Laboratory of Electron Microscopy, Japan Women's University, Mejirodai, Bunkyo-ku, Tokyo,² Department of Infectious Diseases, School of Medicine, Kitasato University, Kitasato, Sagamihara-shi, Kanagawa, Japan³

Received 17 May 2004/ Returned for modification 10 August 2004/ Accepted 25 October 2004

The in vitro activity of tebipenem (TBM), a new oral carbapenem antibiotic, against Streptococcus pneumoniae clinical isolates (n = 202) was compared with those of 15 reference agents. The isolates were classified into five genotypic classes after PCR identification of abnormal pbp1a, pbp2x, and pbp2b genes: (i) penicillin-susceptible S. pneumoniae (PSSP) isolates with no abnormal pbp genes (n = 34; 16.8%), (ii) genotypic penicillin-intermediate S. pneumoniae (gPISP) isolates with only an abnormal pbp2x gene [gPISP (2x)] (n = 48; 23.8%), (iii) gPISP isolates with abnormal pbp1a and pbp2x genes (n = 32; 15.8%), (iv) gPISP isolates with abnormal pbp2x and pbp2b genes (n = 16; 7.9%), and (v) genotypic penicillin-resistant S. pneumoniae (gPRSP) isolates with three abnormal pbp genes (n = 72; 35.6%). The majority of the strains tested had mefA (n = 59; 29.2%) or ermB (n = 91; 45%) gene-mediating macrolide resistance. For these isolates the MIC at which 90% of isolates are inhibited was significantly lower for TBM than for the reference oral antibiotics, as follows: 0.002 µg/ml for PSSP, 0.004 µg/ml for gPISP (2x), 0.016 µg/ml for gPISP (isolates with abnormal pbp1a and pbp2x genes and isolates with abnormal pbp2x and pbp2b genes), and 0.063 µg/ml for gPRSP. In addition, TBM showed excellent bactericidal activity against gPRSP isolates, which exhibited a 3-log₁₀ decrease within 2 h when they were incubated with a concentration greater than or equal to the MIC. Inhibition of cell wall synthesis toward the long axis and subsequent cell lysis were observed by scanning electron microscopy after a short-term exposure to TBM, unlike the effects seen with cephalosporins. These data suggest that TBM has potent activity against multidrug-resistant S. pneumoniae, the causative pathogen of community-acquired respiratory tract infections.

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