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

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Abstract
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-log 10 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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