Antibiotic susceptibility in relation to penicillin-binding protein genes and serotype distribution of Streptococcus pneumoniae strains responsible for meningitis in Japan, 1999 to 2002

The antibiotic susceptibilities, genotypes of penicillin (PEN)-binding protein genes (pbp), and serotype distributions of Streptococcus pneumoniae isolates from meningitis patients were investigated by a nationwide surveillance group in Japan between 1999 and 2002. We analyzed 146 isolates from children (less than or equal to17 years old) and 73 from adults (greater than or equal to18 years old). Isolates with or without abnormal pbpla, pbp2x, or pbp2b genes identified by PCR were classified into six genotype patterns and 90% MIC (MIC90) values for PEN: (i) strains with three normal genes (17.2% of isolates; MIC90, 0.031 mug/ml); (ii) strains with abnormal pbp2x (22.1%, 0.063 mug/ml); (iii) strains with abnormal pbp2b (1.0%, 0.125 mug/ml); (iv) strains with abnormal pbp2x and pbp2b (7.4%, 0.25 mug/ml); (v) strains with abnormal pbpla and pbp2x (12.7%, 0.25 mug/ml); and (vi) strains with three abnormal PBP genes (39.7%, 4 mug/ml), which are termed genotypic PEN-resistant S. pneumoniae (gPRSP). Panipenem, a carbapenem, showed an excellent MIC,, (0.125 mug/ml) against gPRSP, followed by meropenem and vancomycin (0.5 mug/ml), cefotaxime and ceftriaxone (1 mug/ml), and ampicillin (4 mug/ml). Strains of gPRSP were significantly more prevalent in children (45.2%) than in adults (27.4%). The most frequent serotypes were 6B, 19F, 23F, 6A, and 14 in children and 23F, 22, 3, 10, 6B, and 19F in adults. Serotypes 6B, 6A, 19F, 23F, and 14 predominated among gPRSP. In children, 7- and 11-valent pneumococcal conjugate vaccines would cover 76.2 and 81.3% of isolates, respectively, although coverage would be lower in adults (43.9 and 56.0%, respectively). These findings suggest the need for early introduction of pneumococcal conjugate vaccines and continuous bacteriological surveillance for meningitis.