Antibiotic susceptibility and resistance gene analysis of Haemophilus influenza in clinical tebipenem-pivoxil studies in pediatric patients using PCR method

We isolated 158 Haemophilus influenzae strains from pediatric patients enrolled in Phase II and III clinical studies of tebipenem pivoxil(TBPM-PI), and identified them as causative pathogens. These consisted of 112 isolates from patients with acute otitis media(AOM), 16 from those with acute sinusitis, and 30 from those with pneumonia. Mutation(s) of the ftsI gene encoding PBP3 involved in β-lactam resistance were identified in all isolates and classified into six groups based on genetic mutation. gBLNAR strains predominated at 51.9%, followed by gLow-BLNAR at 8.2%, gBLPACR-II at 1.9%, and gBLPACR-I at 0.6%. gBLNAS accounted for only 36.7%. The TBPM MIC₉₀ against gBLNAR was 1.0 μg/mL, an excellent result, following that of cefditoren at 0.25 μg/mL. MIC₉₀ of other oral antibiotics against gBLNAR were 8 μg/mL for ampicillin and faropenem and 32 μg/mL for amoxicillin and cefdinir. Of H. influenzae strains, 94.9% were nontypable, without a polysaccharide capsule. Sequencing of the ftsI gene suggested that further substitution of amino acids at other sites had gradually begun. A comparison of the DNA restriction pattern by PFGE after digestion with SmaI for randomized gBLNAR showed significant diversity. These results suggest that TBPM is bacteriologically efficacious against AOM and other pediatric respiratory infections caused by gBLNAR.