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Antimicrobial Agents and Chemotherapy, May 2004, p. 1488-1494, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1488-1494.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibiotic Susceptibility in Relation to Penicillin-Binding Protein Genes and Serotype Distribution of Streptococcus pneumoniae Strains Responsible for Meningitis in Japan, 1999 to 2002

Kimiko Ubukata,1* Naoko Chiba,1 Keiko Hasegawa,1 Reiko Kobayashi,2 Satoshi Iwata,3 and Keisuke Sunakawa1

Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku,1 Department of Pediatrics, Tokyo National Medical Center, Higashigaoka, Meguro-ku, Tokyo,3 Pharmaceutical Center, Meiji Seika Kaihsha, Morookacho, Kohoku-ku, Yokohama, Japan2

Received 5 September 2003/ Returned for modification 30 November 2003/ Accepted 31 January 2004

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 (<=17 years old) and 73 from adults (>=18 years old). Isolates with or without abnormal pbp1a, 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 µg/ml); (ii) strains with abnormal pbp2x (22.1%, 0.063 µg/ml); (iii) strains with abnormal pbp2b (1.0%, 0.125 µg/ml); (iv) strains with abnormal pbp2x and pbp2b (7.4%, 0.25 µg/ml); (v) strains with abnormal pbp1a and pbp2x (12.7%, 0.25 µg/ml); and (vi) strains with three abnormal PBP genes (39.7%, 4 µg/ml), which are termed genotypic PEN-resistant S. pneumoniae (gPRSP). Panipenem, a carbapenem, showed an excellent MIC90 (0.125 µg/ml) against gPRSP, followed by meropenem and vancomycin (0.5 µg/ml), cefotaxime and ceftriaxone (1 µg/ml), and ampicillin (4 µg/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.

* Corresponding author. Mailing address: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. Phone: (813) 5791-6385. Fax: (813) 5791-6386. E-mail: ubukatak{at}lisci.kitasato-u.ac.jp.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1488-1494, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1488-1494.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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