Antibiotic susceptibility and resistance gene analysis of Streptococcus pneumoniae in clinical tebipenem-pivoxil studies in pediatric using PCR method

Among Streptococcus pneumoniae isolates from pediatric patients in Phase II and III clinical studies of tebipenem pivoxil (TBPM-PI) considered to be causative pathogens, 117 isolates were from patients with acute otitis media, 13 from those with acute sinusitis, and 21 from those with pneumonia, among the 151 strains found. We analyzed for i) pbp and macrolide-resistant genes, ii) susceptibility to antibiotics including TBPM, and iii) capsular type related to pathogenicity. The gPISP (pbp2x) isolate was identified the most at 41.1%, followed by gPRSP (pbp1a + 2x + 2b) at 34.4% and gPISP (pbp1a + 2x) at 12.6%, 94.0% of all strains had some genetic mutation and a macrolide-resistant mef (A) or erm (B) gene. TBPM showed antibacterial activity at 0.001 to 0.008 μ g/mL against gPISP (pbp2x), 0.004 to 0.031 μ g/mL against gPISP (pbp1a + 2x), and 0.008 to 0.125 μ g/mL against gPRSP, making it superior to the activity of most of antibiotics. TBPM antibacterial activity was comparable to that of panipenem. Concerning the capsular type of strains isolated from AOM patients, gPISP (pbp2x) serotype 3 composed 23.1%, followed by serotypes 19F, 6B, 14, and then 23F, among which gPRSP predominated. The coverage of isolates by 7-valent pneumococcal conjugate vaccine (7PCV) was only 48.8%. In conclusion, we expected TBPM to be bacteriological by effective against pneumococcal infection caused by gPISP and gPRSP, including AOM and pneumonia in pediatric patients.