日本化学療法学会雑誌第59巻第6号
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1 P P Streptococcus pneumoniae S. pneumoniae Key words Streptococcus pneumoniae
2 Fig. 1. Capsular swelling reaction of S. pneumoniae type 6B. Cells are stained dark blue using a methylene blue. Capsule is observed outside of cell wall. I PRSP Streptococcus pneumoniae μ S. pneumoniae II
3 Table 1. List of 93 capsular polysaccharide serotypes in S. pneumoniae Type group Type group Type group Type group (25F, 25A) (15F, 15A, 15B, 15C) 28 (28F, 28A) 41 (41F, 41A) 4 16 (16F, 16A) (17F, 17A) (6A, 6B, 6C, 6D) 18 (18F, 18A, 18B, 18C) 32 (32F, 32A) 44 7 (7F, 7A, 7B, 7C) 19 (19F, 19A, 19B, 19C) 33 (33F, 33A, 33B, 33C, 33D) (9A, 9L, 9N, 9V) (35F, 35A, 35B, 35C) 47 (47F, 47A) 10 (10F, 10A, 10B, 10C) 22 (22F, 22A) (11F, 11A, 11B, 11C,11D, 11E) 23 (23F, 23A, 23B) (12F, 12A, 12B) 24 (24F, 24A, 24B) 38 Circles indicate the serotypes contained in PCV7. Circles and squares indicate the serotypes contained in PPV23. (%) Proportion of IPD B 1 23F 5 19F 6A 19A 9V 18C 2 4 7F 12F 3 12A B 45 Serotype Fig. 2. Proportion of IPD due to the most common serotypes spread globally in young children. Haemophilus influenzae
4 Number of patients (n) Non-survivors Survivors Sequela ( ) Survivors Sequela ( ) Survivors Sequela (unknown) outcome unknown 0 6M 7M 11M 1y 2y 3y 4y 5 9y 10s 20s 30s 40s 50s 60s 70s 80s 90s Patient age Fig. 3. Number of patients with IPD by age and outcome. III IPD P P
5 (%) Underlying disease ( ) Children Underlying disease ( ) Unknown Underlying disease ( ) P 0.01 Adults Underlying disease ( ) Unknown Fatality Sequelae ( ) outcome unknown Sequelae ( ) Sequelae unknown Fig. 4. Outcomes based on presence or absence of underlying diseases in IPD patients. Median or % (25/75 percentiles) and (no./total) Table 2. Clinical laboratory findings associated with fatal outcome in adults with IPD 40) Non-survivors (n 43) Survivors (n 147) Univariate analysis OR a P value WBC (10 9 cells/l) b 5.1 ( ) (37/43) 13.2 ( ) (136/147) cells/l 48.6% (18/37) 11.0% (15/136) 7.64 ( ) P C-reactive protein (mg/dl) 24.8 ( ) (36/43) 20.6 ( ) (131/147) 15 mg/dl 77.8% (28/36) 65.6% (86/131) 1.83 ( ) P PLT (10 9 cells/l) b 119 (69 171) (36/43) 197 ( ) (134/147) /L 55.6% (20/36) 23.1% (31/134) 4.15 ( ) P a Data are expressed as odds ratio values (95% confidence interval). b WBC, white blood cell count; PLT, platelet count. 25 (%) 20 gpssp: 14.1% gpisp (pbp2b): 1.0% gpisp (pbp2x): 19.9% gpisp (pbp1a 2x): 12.6% gpisp (pbp2x 2b): 6.3% gprsp (pbp1a 2x 2b): 46.1% B 19F 14 23F 4 9V 18C 6A 19A 1 3 7F 12F Other NT PCV7 (75.4%) PCV13 (93.7%) Fig. 5. Serotype distribution and resistance genes identified by PCR in S. pneumoniae isolated from children. Other includes serotypes of 15B, 23A, 8, 24, 34, 35, and 38, respectively. NT, non-typeable
6 25 (%) 20 gpssp: 24.6% gpisp (pbp2b): 12.0% gpisp (pbp2x): 28.6% gpisp (pbp1a 2x): 10.0% gpisp (pbp2x 2b): 7.6% gprsp (pbp1a 2x 2b): 17.3% F 3 6B F 9V 10A 22F 19F 19A 15B 1 Other- 6A 1 PPV23 (85.4%) 23A Other- NT 2 Fig. 6. Serotype distribution and resistance genes identified by PCR in S. pneumoniae isolated from adults. Other-1 includes serotypes of 9N, 11A, 33, 18C, 20, 2, 7F, 8; Other-2 includes serotypes of 35, 7C, 15A, 38, 15C, 31, 16, and 36, respectively. Serotype 0% 20% 40% 60% 80% 100% 3 (n 34) 4 (n 21) 14 (n 23) 6A (n 15) Meningitis Pneumonia Sepsis 6B (n 31) 12F (n 43) 15 (n 13) Meningitis Pneumonia Pneumonia and Sepsis Sepsis Empyema or Pleuritis Other Fig. 7. Relationship between pneumococcal capsular types and the diseases in adults. IV IPD gprsp β pbp1a pbp2x pbp2b pbp1a 2x 2b pbp2x
7 (A) Marker A B C DMarker (B) Osaka : : Ibaragi Tokyo Aichi Kanagawa Fig. 8 A) PFGE patterns digested with ApaI enzyme for chromosomal DNA from serotype 12F isolates. A, gpisp (pbp2b) (Lane 1 19); B, gpssp (Lane 20 24); C, gpisp (pbp2x+2b) (Lane 25, 26); D, gprsp (pbp1a+2x+2b) (Lane 27). B) Plot of serotype 12F isolates in Japan, 2003 to pbp2b pbp2x
8 Table 3. Association of serotypes with multilocus sequence typing profiles and genetic pbp patterns among S. pneumoniae strains 51) Serotype CC ST Genotype No. of strains Allele gene First reported aroe gdh gki recp spi xpt ddl Year Country (city) gpssp x gpssp UK 6A gprsp Korea gprsp China x UN Singapore 6B gprsp Spain gprsp Korea x, 1a 2x Japan (Okayama) gprsp Singapore x, 1a 2x Japan (Kurume) gprsp, 1a 2x UK x Japan (Hyogo) 6C x Japan (Hyogo) x x Japan (Kurume) 9V x, 2x 2b Vietnam x F b UN Japan (Osaka) gprsp Norway gprsp Taiwan gprsp, 1a 2x a 2x Australia, USA a 2x Japan (Hyogo) 15A a 2x Sweden 15B a 2x Netherlands 15C x Netherlands 19F gprsp Taiwan gprsp Taiwan 19A x, 1a 2x USA x Czech 23F gprsp Taiwan gprsp Japan gprsp Sweden gprsp, 2x 2b Colombia 23A gprsp, 2x 2b Colombia New sequence types (STs) are shown in bold face and underlined. CC, clonal complex. Year, first isolation year of the same ST clone referred from the MLST database. Country, first country of isolation for the same ST clone referred from the MLST database. V Apa pbp2b pbp2x 2b
9 Antibiotic pressure Competition between strains Vaccination pressure Genetic mutation or Genetic recombination Selection of strain with high virulence Selection of strain with high resistance Capsular Switching Fig. 9. Evolution of S. pneumoniae under the selective pressures such as antimicrobial agents and vaccines. pbp1a pbp2x VI
10 β pbp μ pbp2x pbp2x pbp1a in vitro Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae β Streptococcus pneumoniae In Streptococcus pneumoniae Streptococcus pneumoniae
11 Streptococcus pneumoniae Haemophilus influenzae Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae
12 Streptococcus pneumoniae Streptococcus pneumoniae Streptococcus pneumoniae P P S. pneumoniae
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1 2 µ Streptococcus pneumoniae µ S. pneumoniae µ S. pneumoniae pbp β β pbp1a pbp2x pbp2b pbp mefe ermb pbp pbp1a pbp2x pbp2b pbp pbp pbp pbp 2x pbp1a pbp2x pbp 2b mefe ermb pbp β pbp2x β β β µ µ pbp3 µ
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