70( 70 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. Meropenem 2002 * * * * * * * * * * * * * * * * * * * * * * NTT

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 71( 71 ) * * * * 2003 12 22 Meropenem (MEPM) 28 2002 2557 1500 899 158 (MIC) 1. MEPM Haemophilus influenzae Pseudomonas aeruginosa MEPM MIC 90 imipenem (IPM) ciprofloxacin (CPFX) MEPM methicillinresistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis 2. b - (ESBL) Escherichia coli 4 (3.1%) Klebsiella pneumoniae 2 (1.9%) MEPM MEPM 7

72( 72 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. meropenem (MEPM) 1 3) 1995 4) MEPM 1987 imipenem/cilastatin (IPM/CS) 5) 1993 panipenem/betamipron (PAPM/BP) 6) MEPM biapenem (BIPM) 7) MEPM 8) PAPM, IPM dehydropeptidase-i (DHP-I) 9) MEPM IPM, PAPM 10) MEPM 90 7 2002 28 MEPM I. 1. 9 11 2002 Escherichia coli, Citrobacter spp., Klebsiella pneumoniae, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter spp., Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae b- b-lactamase producing ampicillin (ABPC)-susceptible H. influenzae (BLNAS), b -lactamase non-producing ABPCresistant H. influenzae (BLNAR) Methicillin (DMPPC)-susceptible Staphylococcus aureus (MSSA), DMPPC-resistant S. aureus (MRSA), DMPPC-susceptible Staphylococcus epidermidis (MSSE), DMPPC-resistant S. epidermidis (MRSE), coagulase-negative staphylococci CNS, S. epidermidis penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group (Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci (Streptococcus oralis, Streptococcus mitis, Streptococcus salivarius), Enterococcus faecalis, Enterococcus spp. E. faecalis Bacteroides fragilis group, Prevotella spp., Peptostreptococcus spp., Fusobacterium spp. 2. NCCLS 11) S. aureus oxacillin (MPIPC) MIC 2 m g/ ml MSSA, 4 m g/ml MRSA S. epidermidis, MPIPC MIC 0.25 m g/ml MSSE, 0.5 m g/ml MRSE S. pneumoniae, benzylpenicillin (PCG) MIC 0.06 m g/ml PSSP, 0.12 1 m g/ml PISP, 2 m g/ml

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 73( 73 ) PRSP H. influenzae b- ABPC MIC 2 m g/ml BLNAR, 1 m g/ml BLNAS 3. MIC MEPM, IPM, PAPM, BIPM, cefazolin (CEZ), cefaclor (CCL), cefotiam (CTM), cefmetazole (CMZ), cefotaxime (CTX), ceftriaxone (CTRX), ceftazidime (CAZ), cefozopran (CZOP), cefepime (CFPM), flomoxef (FMOX), MPIPC, PCG, ABPC, piperacillin (PIPC), sulbactam/ampicillin (SBT/ ABPC), sulbactam/cefoperazone (SBT/CPZ), gentamicin (GM), amikacin (AMK), arbekacin (ABK), tobramycin (TOB), aztreonam (AZT), vancomycin (VCM), teicoplanin (TEIC), ciprofloxacin (CPFX), clindamycin (CLDM), minocycline (MINO), linezolid (LZD) 4. NCCLS 11 13) N. gonorrhoeae (MIC) MIC Streptococcus spp., L. monocytogenes N. meningitidis (2 v/v%) cationadjusted Mueller Hinton broth (CAMHB, DIFCO) H. influenzae CAMHB (5 g/l), NAD (15 mg/l), (15 mg/l) (2 v/v%) CAMHB (5 mg/l), K 1 (1 mg/l), (5 v/v%) Brucella broth 128 0.06 m g/ml 5 10 4 CFU/well, 10 5 CFU/well Streptococcus spp., H. influenzae 35 C 20 24 L. monocytogenes 35 C 16 20 N. meningitidis 35 C 24 5% 35 C 16 24 35 C 46 48 N. gonorrhoeae MIC 1% defined growth supplement cysteine GC agar base (BBL) 128 0.001 m g/ml 10 4 CFU/spot 35 C 20 24 5% 5. b - H. influenzae b - 6. b - (ESBL) NCCLS 11) CAZ AZT MIC 2 m g/ml ESBL ESBL PCR b -lactamase Real-time PCR Sequence Detection System 7000, Applied Biosystems, Primer 1 TEM- 14) SHV- 14) Toho- CTX- M-2 15) CTX-M-10 16) CTX-M- 14 17) 5

74( 74 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 1. b- (ESBL) 50 m l 100 C 10 15,000 rpm 5 DNA PCR DNA 1m l, Primer 50 pmol, SYBR Green PCR Master Mix (Applied Biosystems) 25 m l 50 m l 50 C 2 94 C 10 PCR PCR Tm PCR 7. (PFGE) ISHII 18) TENOVER 19) XbaI II. 1. 2557 2 867 (33.9%) 512 (20.0%) (53.9%) 2. MIC 3 37 MIC MIC 50% MIC (MIC 50 ), 90% MIC (MIC 90 ) MIC 90 MEPM (1) 1) E. coli 3: 129 16 MEPM 0.25 m g/ml MEPM CFPM CFPM MIC 16 mg/ml: NCCLS Intermediate Resistant 3 (2.3%) MEPM MIC 90 0.06 m g/ml PAPM 2 IPM BIPM 3 Citrobacter spp. 4: 93 16 MEPM 1 m g/ml MEPM CPFX CPFX (MIC 2 m g/ml) 4 (4.3%) MEPM MIC 90

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 75( 75 ) 2. 0.12 m g/ml IPM, PAPM, BIPM 4 K. pneumoniae 5: 105 16 MEPM 0.25 m g/ml MEPM CFPM, CPFX CFPM (MIC 16 m g/ml) 2 (1.9%) MEPM MIC 90 0.06 m g/ml PAPM 3 IPM BIPM 4 Enterobacter spp. 6: 105 16 MEPM 1 m g/ml MEPM CPFX CPFX (MIC 2 m g/ml) 10 (9.5%) MEPM MIC 90 0.5m g/ml IPM, PAPM BIPM 2 (MIC 8 m g/ml) PAPM 1 (1.0%),

76( 76 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 3. E. coli 129 MIC MIC 50, MIC 90 4. Citrobacter spp. 93 MIC MIC 50, MIC 90 5. K. pneumoniae 105 MIC MIC 50, MIC 90

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 77( 77 ) 6. Enterobacter spp. 105 MIC MIC 50, MIC 90 7. S. marcescens 106 MIC MIC 50, MIC 90 8. P. mirabilis 64 MIC MIC 50, MIC 90

78( 78 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. BIPM 2 (1.9%) S. marcescens 7: 106 16 MEPM MIC 90 1 m g/ml MEPM CFPM, CPFX PAPM MIC 90 4 mg/ml MEPM MIC 90 PAPM 2 IPM BIPM 3 (MIC 8 m g/ml) MEPM 2 (1.9%), IPM 11 (10.4%), PAPM 7 (6.6%), BIPM 14 (13.2%) P. mirabilis 8: 64 16 AZT MEPM, CAZ AZT (MIC 128 m g/ml) 1 (1.6%) MEPM 1 m g/ml MEPM MIC 90 0.25 mg/ml IPM PAPM 4 BIPM 5 AZT, MEPM, CAZ CFPM CFPM (MIC 16 m g/ml) 4 (6.3%) (MIC 8 m g/ml) IPM 6 (9.4%), PAPM 4 (6.3%), BIPM 8 (12.5%) P. vulgaris 9: 38 16 CPFX, MEPM MEPM 1 m g/ml MEPM MIC 90 0.5 m g/ml BIPM 4 IPM PAPM 5 CPFX, MEPM CFPM CFPM (MIC 128 m g/ml) 3 (7.9%) (MIC 8 m g/ml) IPM 9 (23.7%), PAPM 7 (18.4%), BIPM 8 (21.1%) M. morganii 10: 83 16 MEPM CFPM MEPM 1 m g/ml MEPM, CFPM CPFX CPFX (MIC 2 m g/ml) 5 (6.0%) MEPM MIC 90 0.5 m g/ml PAPM BIPM 3 IPM 4 (MIC 8 m g/ml) IPM 9 (10.8%), PAPM 2 (2.4%) Providencia spp. 11: 42 16 AZT, MEPM AZT (MIC 16 m g/ml) 2 MEPM (MIC 8 m g/ml) 1 (2.4%) MEPM 1 AMK, AZT MEPM MIC 90 0.5 m g/ml IPM, PAPM BIPM 3 AZT, MEPM CZOP CFPM 2 (MIC 16 m g/ml) 3 (7.1%) (MIC 8 m g/ml) IPM 3 (7.1%), PAPM 1 (2.4%), BIPM 2 (4.8%) 2) P. aeruginosa 12: 280 16 MEPM, TOB GM MIC 90 8 m g/ml MEPM MIC 90 IPM BIPM 1 PAPM 2 (MIC 16 mg/ml) MEPM 26 (9.3%) IPM 61 (21.8%), PAPM 99 (35.4%), BIPM 38 (13.6%) (IPM 16 m g/ml, CPFX 4 m g/ml, AMK 32 mg/ml) 10 (3.6%)

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 79( 79 ) 9. P. vulgaris 38 MIC MIC 50, MIC 90 10. M. morganii 83 MIC MIC 50, MIC 90 11. Providencia spp. 42 MIC MIC 50, MIC 90

80( 80 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. B. cepacia 13: 24 16 MEPM CPFX CPFX (MIC 2 m g/ml) 15 MEPM 4mg/ml (MIC 8 m g/ml) MEPM MIC 90 4 m g/ml IPM BIPM 1 PAPM 2 (MIC 8 m g/ml) IPM 5 (20.8%), PAPM 21 (87.5%), BIPM 12 (50.0%) Acinetobacter spp. 14 99 16 MINO, BIPM IPM, MEPM MEPM MIC 90 2 m g/ml BIPM MIC 90 0.5 m g/ml IPM 1 MEPM 2 PAPM 3 MINO (MIC 8 m g/ml) 3 (3.0%) (MIC 8 m g/ml) MEPM, IPM, BIPM 2 (2.0%), PAPM 3 (3.0%) 3) M. catarrhalis 15: 77 16 MEPM 0.008 m g/ml MEPM MIC 90 0.008 m g/ml PAPM 2 IPM BIPM 3 CPFX 0.25 m g/ml N. gonorrhoeae 16: 64 16 CTRX, MEPM, PIPC, SBT/CPZ MEPM 0.12 m g/ml MEPM MIC 90 0.12 m g/ml PAPM 2 IPM BIPM 3 CPFX MIC 90 32 m g/ml (MIC 1 m g/ml) 48 (75.0%) N. meningitidis 1 16 4 MIC MEPM 0.008 m g/ml, IPM, BIPM 0.015 m g/ml, PAPM 0.03 m g/ml MIC CTRX, CPFX 0.004 m g/ml, CFPM 0.008 m g/ml, CAZ, CZOP, FMOX, PCG, PIPC, SBT/CPZ 0.06 m g/ml, ABPC 0.12 m g/ml, AMK 8 mg/ml H. influenzae b- 17: 24 16 CPFX, CTRX, MEPM, SBT/CPZ, CTX MEPM 1 m g/ml MEPM MIC 90 1 m g/ml IPM PAPM 1 BIPM 3 (MIC 8 m g/ml) IPM 2 (8.3%), BIPM 5 (20.8%) H. influenzae (BLNAS) 18: 98 16 CTRX, CPFX, CTX, MEPM, PIPC MEPM 0.12 m g/ml MEPM MIC 90 0.12 m g/ml PAPM 3 IPM 4 BIPM 5 BIPM (MIC 8 m g/ml) 8 (8.2%), CPFX (MIC 2 m g/ml) 1 (1.0%) H. influenzae (BLNAR) 19: 68 16 CPFX, PIPC, CTRX, SBT/CPZ, MEPM MEPM 2 m g/ml MEPM MIC 90 1 mg/ml IPM PAPM 2 BIPM 4 (MIC 8 m g/ml) IPM 4 (5.9%), PAPM 3

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 81( 81 ) 12. P. aeruginosa 280 MIC MIC 50, MIC 90 13. B. cepacia 24 MIC MIC 50, MIC 90 14. Acinetobacter spp. 99 MIC MIC 50, MIC 90

82( 82 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 15. M. catarrhalis 77 MIC MIC 50, MIC 90 16. N. gonorrhoeae 64 MIC MIC 50, MIC 90 17. H. influenzae b - 24 MIC MIC 50, MIC 90

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 83( 83 ) 18. H. influenzae (BLNAS) 98 MIC MIC 50, MIC 90 19. H. influenzae (BLNAR) 68 MIC MIC 50, MIC 90 (4.4%), BIPM 39 (57.4%) (2) 1) MSSA 20: 80 21 MEPM 4 0.25 m g/ml 4 MINO MIC 90 0.25 m g/ml MINO (MIC 8m g/ml) 2 (2.5%) MRSA 21: 88 21 MRSA VCM, ABK, TEIC, LZD MIC 90 2 4 m g/ml MIC 90 4 64 m g/ml VCM (MIC 8mg/ml) MSSE 22: 25 21 MEPM 4 0.25 m g/ml 4 MPIPC, ABK MINO MIC 90 0.25 m g/ml

84( 84 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 20. S. aureus (MSSA) 80 MIC MIC 50, MIC 90 21. S. aureus (MRSA) 88 MIC MIC 50, MIC 90 MRSE 23: 101 21 MINO, ABK, VCM, LZD MIC 90 1 4 m g/ml MIC 90 4 16 mg/ml MINO (MIC 8 m g/ml) 8 (7.9%) VCM (MIC 16 m g/ml) CNS S. epidermidis 24: 48 21 ABK, VCM, LZD MIC 90 0.5 4 m g/ml MIC 90 4

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 85( 85 ) 22. S. epidermidis (MSSE) 25 MIC MIC 50, MIC 90 23. S. epidermidis (MRSE) 101 MIC MIC 50, MIC 90 8 m g/ml 4 (MIC 8 m g/ml) MPIPC-resistant CNS 2) PSSP 25: 75 16 MEPM 4 0.06 m g/ml PCG 4 PCG TEIC 0.12 m g/ml PISP 26: 42 16 MEPM 4 0.5 m g/ml TEIC TEIC,

86( 86 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 24. CNS S. epidermidis 48 MIC MIC 50, MIC 90 25. S. pneumoniae (PSSP) 75 MIC MIC 50, MIC 90 4 VCM MIC 90 0.5 m g/ml PRSP 27: 48 16 MEPM 4 0.5 mg/ml TEIC TEIC, 4 VCM MIC 90 0.5 m g/ml S. milleri group 28: 45 16 MEPM 4 0.12 m g/ml PCG TEIC 4 PCG TEIC ABPC MIC 90 0.12 m g/ml S. pyogenes 29: 67 16 MEPM 4 CZOP, CFPM, PCG, ABPC, PIPC, CTX CTRX 0.06 m g/ml

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 87( 87 ) 26. S. pneumoniae (PISP) 42 MIC MIC 50, MIC 90 27. S. pneumoniae (PRSP) 48 MIC MIC 50, MIC 90 28. S. milleri group 45 MIC MIC 50, MIC 90

88( 88 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 29. S. pyogenes 67 MIC MIC 50, MIC 90 30. S. agalactiae 79 MIC MIC 50, MIC 90 TEIC MIC 90 0.12 m g/ml S. agalactiae 30: 79 16 MEPM 4 0.06 m g/ml 4 PCG 0.12 m g/ml Viridans group streptococci 31: 27 16 MEPM 4 4 m g/ml TEIC 4 PCG, ABPC VCM MIC 90 1 mg/ml 3) E. faecalis 32: 102 16 TEIC 1 m g/ml VCM, ABPC, IPM, LZD, PAPM, MEPM, BIPM PIPC MIC 90 2 8 m g/ml VCM (MIC 16 mg/ml) MIC 90 64 m g/ml

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 89( 89 ) 31. Viridans group streptococci 27 MIC MIC 50, MIC 90 32. E. faecalis 102 MIC MIC 50, MIC 90 Enterococcus spp. E. faecalis 33: 70 16 VCM, TEIC, LZD MIC 90 1 4 m g/ml VCM (MIC 16 m g/ml) MIC 90 4 64 m g/ml L. monocytogenes 2 16 4 MIC-range MEPM 0.12 m g/ml, IPM, PAPM 0.06 m g/ml, BIPM 0.06 0.12 m g/ml 4 PCG, ABPC MIC-range 0.25 0.5 m g/ml MIC-range CTX 16 64 m g/ml, CTRX, CFPM 32 64 m g/ml, CZOP, CFPM 16 32 m g/ml, FMOX 8 16 m g/ml, PIPC 2 4 m g/ml, CPFX, VCM 1 mg/ml, AMK 0.5 1 m g/ml

90( 90 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 33. Enterococcus spp. E. faecalis 70 MIC MIC 50, MIC 90 34. B. fragilis group 63 MIC MIC 50, MIC 90 (3) B. fragilis group 34: 63 16 MEPM 4 MEPM MIC 90 4 m g/ml 4 SBT/ABPC, SBT/CPZ MIC 90 16 m g/ml CLDM MIC 90 128 m g/ml MIC 0.06 8 mg/ml 128 128 m g/ml 2 (MIC 8 m g/ml) MEPM IPM 4 (6.3%), PAPM 7 (11.1%), BIPM 3 (4.8%) MEPM (MIC 16 m g/ml) 1 Prevotella spp. 35: 43 16 MEPM 4 MEPM MIC 90 0.25 m g/ml 2 m g/ml 4 SBT/ABPC, SBT/CPZ, FMOX, CMZ MIC 90 8 m g/ml CLDM MIC 90 128 m g/ml MIC 0.06 2 m g/ml 128 mg/ml 2

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 91( 91 ) 35. Prevotella spp. 43 MIC MIC 50, MIC 90 36. Peptostreptococcus spp. 35 MIC MIC 50, MIC 90 37. Fusobacterium spp. 10 MIC MIC 50, MIC 90

92( 92 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. (MIC 8 mg/ml) IPM PAPM 2 (4.7%) Peptostreptococcus spp. 36: 35 16 MEPM 4 MEPM MIC 90 0.25 m g/ml 2 m g/ml 4 ABPC, SBT/ABPC MIC 90 0.5 m g/ml CLDM MIC 90 2 m g/ml (MIC 128 m g/ml) 1 (2.9%) Fusobacterium spp. 37: 10 16 MEPM 4 0.25 m g/ml 4 CLDM PIPC MIC 90 0.06 mg/ml 0.12 m g/ml 3. MIC (1) 1 4 MIC 90 MEPM MIC 90 3 6 2 5 38. ESBL E. coli K. pneumoniae 1. MIC 90

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 93( 93 ) K. pneumoniae 2 (1.9%), E. coli 4 (3.1%) ESBL 38 PCR ESBL K. pneumoniae SHV- - E. coli Toho- CTX-M- b - 2 E. coli 2 (No. 2, No. 3) PFGE No. 2 No. 3 (2) P. aeruginosa 39 CPFX IPM (MIC 16 m g/ml) 61 MEPM CPFX 24 39.3% PAPM, BIPM 96.7%, 62.3% MEPM (MIC 16 m g/ml) 26 CPFX 50% CPFX (MIC 4 m g/ml) 54 BIPM MEPM 24.1% 25.9% IPM PAPM 44.4% 59.3% 3 MEPM MIC MEPM MIC 1 IPM 83.9% 235 /280 PAPM 96.1% 269 /280 BIPM 33.2% 93 /280 2. ESBL E. coli K. pneumoniae PFGE 39.

94( 94 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 3. P. aeruginosa MEPM MIC 40 P. aeruginosa MEPM CPFX MEPM CPFX (3) H. influenzae 4 H. influenzae MIC b - ABPC 4 MIC BLNAR BLNAS MEPM 2 m g/ml BLNAR 5 7 MEPM MIC MEPM MIC 1 b - IPM PAPM 91.7% 22 /24 BIPM 100.0% 24 /24 BLNAS IPM PAPM 94.9% 93 /98 BIPM 96.9% 95 /98 BLNAR IPM 92.6% 63 /68 PAPM 94.1% 64 /68 BIPM 100.0% 68 /68 (4) 16 423 16.5% H. influenzae 78 S. pneumoniae 57 M. catarrhalis 38 P. aeruginosa 37 (49.6%) 10

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 95( 95 ) 40. P. aeruginosa 4. H. influenzae MIC

96( 96 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 5. H. influenzae b-lactamase MEPM MIC 6. H. influenzae (BLNAS) MEPM MIC

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 97( 97 ) 7. H. influenzae (BLNAR) MEPM MIC MEPM MIC-range MIC 50 MIC 90 41 MIC 50 MIC 90 2 30 P. aeruginosa, M. catarrhalis, BLNAS BLNAR IPM, PAPM, CZOP FMOX MIC-range, MIC 50 MIC 90 42 MEPM III. 2002 28 1500 899 158 2557 MEPM MEPM MIC 90 6 3 2 5 (MIC 8 m g/ml) 660 IPM 38 PAPM 22 BIPM 34 MEPM S. marcescens 2 Providencia spp. 1 3 20 22) E. coli MEPM PBP2 PBP3

98( 98 ) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 41. MEPM MIC-range, MIC 50, MIC 90 42. MEPM MIC-range, MIC 50, MIC 90

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 99( 99 ) 23) ESBL E. coli 4 (3.1%) K. pneumoniae 2 (1.9%) YAGI 1997 1 1998 1 196 16805 E. coli 9794 K. pneumoniae ESBL E. coli 0.1%, K. pneumoniae 0.3% ESBL 24) 2000 20) E. coli 0.6% 1 /164 K. pneumoniae 4.0% 2 / 50 21) E. coli 5.0% 5 /100 K. pneumoniae 4.0% 2 /50 22) E. coli 0.9% 1 /110 K. pneumoniae 3.4% 3 /89 ESBL E. coli 4 3 2 ESBL MEPM -b - Providencia spp. 1 AZT, AMK CPFX K. pneumoniae, P. vulgaris 21) P. aeruginosa MEPM MIC 90 4 MEPM OprD 25) MEPM OprD MEPM OprD MexAB-OprM 25) MEPM 21 /26 MIC 16 32 m g/ml -b - OprD 2 CPFX 26) 10 (3.6%) 8 MEPM 42 Acinetobacter spp. -b - 27) (MIC 16 m g/ml) 2 (2.0%) MEPM MEPM MIC 50 MIC 90 H. influenzae BLNAR MIC BLNAS MEPM

100(100) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 2 m g/ml 28) MEPM MIC 4 mg/ml BLNAR IPM 11 b- 2 [8.3%], BLNAR 9 [13.2%] PAPM 12 b - 2 [8.3%], BLNAR 10 [14.7%] BIPM 75 b- 8 [33.3%], BLNAS 12 [12.2%], BLNAR 55 [80.9%] BLNAR H. influenzae H. influenzae MEPM H. influenzae PBP3A PBP3B 29) MEPM CTRX, CPFX CPFX 1 N. gonorrhoeae MEPM CPFX (MIC 1 m g/ml) (75.0%) 30) MEPM MSSA MSSE MRSA, MRSE VCM, TEIC, ABK, LZD VCM-intermediate S. aureus (VISA), VCM-resistant S. aureus (VRSA), VCM-resistant enterococci (VRE) S. pneumoniae MIC 0.5 m g/ml E. faecalis ABPC MEPM MIC 90 8 mg/ml 32 m g/ml, 16 m g/ml 31) B. fragilis group MIC 90 4 CLDM 16 m g/ml MEPM MIC 16 m g/ml 3 (4.8%) MIC 90 4 m g/ml Prevotella spp. MIC 90 8 mg/ml MEPM MIC 90 0.25 m g/ml MEPM MIC 90 0.12 0.25 m g/ml MEPM CLDM 3) B. fragilis group, Prevotella spp. B. fragilis group MEPM -b- 32) MEPM 7 MEPM

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 101(101) 51 15 5 1) Meropenem Jpn. J. Antibiotics 49: 175 193, 1996 2) 1997 Meropenem (MEPM) Jpn. J. Antibiotics 52: 695 720, 1999 3) 1999 Meropenem (MEPM) Jpn. J. Antibiotics 54: 145 170, 2001 4) pp. 43 53, 1995 5) pp. 27 34, 1995 6) pp. 35 42, 1995 7) pp. 54 63, 1995 8) Meropenem Chemotherapy 40 (Suppl. 1): 222 237, 1992 9) Meropenem Chemotherapy 40 (Suppl. 1): 123 131, 1992 10) SUNAGAWA, M.; H. MATSUMURA, Y. SUMITA, et al.: Structure features resulting in convulsive activity of carbapenem compounds: Effect of C-2 side chain. J. Antibiotics 48: 408 416, 1995 11) National Committee for Clinical Laboratory Standards: Performance standards for antimicrobial susceptibility testing; Twelfth informational supplement; M100 S12, 2002 12) National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard-fifth edition; M7-A5, 2000 13) National Committee for Clinical Laboratory Standards: Methods for antimicrobial susceptibility testing of anaerobic bacteria; Approved standard-fifth edition; M11-A5, 2001 14) PERILLI, M.; E. DELL AMICO, B. SEGATORE, et al.: Molecular characterization of extended-spectrum betalactamases produced by nosocomial isolates of Enterobacteriaceae from an Italian nationwide survey. J. Clin. Microbiol. 40: 611 614, 2002 15) YAGI, T.; H. KUROKAWA, K. SENDA, et al.: Nosocomial spread of cephem-resistant Escherichia coli strains carrying multiple Toho-1-like beta-lactamase genes. Antimicrob. Agents Chemother. 41: 2606 2611, 1997 16) STEWARD, C. D.; J. K. RASHEED, S. K. HUBERT, et al.: Characterization of clinical isolates of Klebsiella pneumoniae from 19 laboratories using the National Committee for Clinical Laboratory Standards extendedspectrum beta-lactamase detection methods. J. Clin. Microbiol. 39: 2864 2872, 2001 17) MA, L.; Y. ISHII, F. Y. CHANG, et al.: CTX-M-14, a plasmid-mediated CTX-M type extended-spectrum betalactamase isolated from Escherichia coli. Antimicrob. Agents Chemother. 46: 1985 1988, 2002 18) ISHII, Y.; J. ALBA, S. KIMURA, et al.: Rapid pulsed-field gel electrophoresis technique for determination of genetic diversity of Serratia marcescens. J. Infect. Chemother. 8(4): 368 370, 2002 19) TENOVER, F. C.; R. D. ARBEIT, R. V. GOERING, et al.: Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J. Clin. Microbiol. 33: 2233 2239, 1995 20) Cefoselis b- 2000 Pharma Medica 20(5): 168 193, 2002 21) 2002 51(4): 209 232, 2003 22) 2000 2001 panipenem (PAPM) Jap. J. Antibiotics 55(6): 808 826, 2002 23) Meropenem Chemotherapy 40 (Suppl. 1) 90 102, 1992 24) YAGI, T.; H. KUROKAWA, N. SHIBATA, et al.: A preliminary survey of extended-spectrum b -lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan. FEMS Microbiol. Lett. 184: 53 56, 2000 25) Jpn. J. Antibiotics 53: 479 511, 2000 26) 1998 26 5,180 Jpn. J. Antibiotics 53: 387 408, 2000 27) P. aeruginosa Acinetobacter spp. 75(8): 662 670, 2001 28) SAITO, A.; T. INAMATSU, J. OKADA, et al.: Clinical breakpoints in pulmonary infections and sepsis: new antimicrobial agents and supplemental information for some agents already released. J. Infect. Chemother. 5: 223 226, 1999

102(102) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. 29) KANAZAWA, K.; K. NOUDA, M. SUNAGAWA: Structure-activity relationships of carbapenem compounds to anti- Haemophilus influenzae activity and affinity for penicillin-binding proteins: Effect of 1-methyl group and C-2 side chain. J. Antibiotics 50: 162 168, 1997 30) TANAKA, M.; H. NAKAYAMA, H. TUNOE, et al.: A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan. J. Infect. Chemother. 8: 81 86, 2002 31) 45: 711 726, 1997 32) BANDOH, K.; K. UENO, K. WATANABE, et al.: Susceptibility patterns and resistance to imipenem in Bacteroides fragilis group species in Japan. Clin. Infect. Dis. 16 (Suppl. 4): S382 S386, 1993 NATIONWIDE SURVEILLANCE OF PARENTERAL ANTIBIOTICS CONTAINING MEROPENEM ACTIVITIES AGAINST CLINICALLY ISOLATED STRAINS IN 2002 KEIZO YAMAGUCHI Department of Microbiology, Toho University School of Medicine YOSHIKAZU ISHII and MORIHIRO IWATA* Department of Microbiology, Toho University School of Medicine *Department of Laboratory Medicine, Toho University Omori Hospital NAOKI WATANABE and NOBUYUKI UEHARA Department of Clinical Laboratory Medicine, Division of Laboratory Diagnosis, Sapporo Medical University School of Medicine HIROSHI YOSHIDA and TOSHIO SATOH Department of Clinical Laboratory Medicine and Clinical Laboratories, Fukushima Medical University MASAMI MURAKAMI and AYAKO TAKAHASHI* Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine *Clinical Laboratory Center, Gunma University Hospital MINORU YASUJIMA and TAKESHI KASAI Department of Laboratory Medicine, Hirosaki University, School of Medicine AKIRA SUWABE and RITSUKO OBATA* Department of Laboratory Medicine, Iwate Medical University School of Medicine *Department of Central Clinical Laboratories, Iwate Medical University School of Medicine MITSUO KAKU and KEIJI KANEMITSU Division of Molecular Diagnostics, Tohoku University Graduate School of Medicine KOUICHI ITOH and YASUHIRO SHIBUYA Clinical Laboratory Medicine, Jichi Medical School HARUSHIGE KANNO and SETSUKO KUBO Clinical Laboratory, Chiba University Hospital SHIGEFUMI MAESAKI and GIICHI HASHIKITA* Department of Infectious Disease & Infection Control, Saitama Medical School *Department of Laboratory Medicine, Saitama Medical School

Feb. THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 103(103) JUN IGARI and TOYOKO OGURI* Department of Clinical Pathology, Juntendo University School of Medicine *Department of Clinical Laboratories, Juntendo University Hospital MASANORI AIHARA Department of Clinical Pathology, Tenri Hospital SHOHIRO KINOSHITA Clinical Laboratory, Kobe University Hospital JUN OKADA and YOKO TAZAWA Clinical Laboratory, Kanto Medical Center, NTT EC HIDEKI NAKASHIMA and HIROMU TAKEMURA Department of Microbiology, St. Marianna University School of Medicine TOSHINOBU HORII Department of Laboratory Medicine, Hamamatsu University School of Medicine HISASHI BABA Department of Infectious Diseases, Nagoya University School of Medicine SHIOMI ISHIGO Clinical Laboratory, Ogaki Municipal Hospital TOMOHIKO TAMINATO and KIYOSHI NEGAYAMA Department of Laboratory Medicine, Kagawa Medical University MITSUHARU MURASE and HITOSHI MIYAMOTO Clinical Laboratory, Ehime University Hospital NOBUCHIKA KUSANO and EIICHIROU MIHARA Department of Laboratory Medicine, Okayama University Graduate School of Medicine and Dentistry MASAYUKI KAMBE and HIDEYUKI ITAHA Department of Clinical Laboratory Medicine, Hiroshima University, Faculty of Medicine NAOHISA FUJITA and TOSHIAKI KOMORI Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine JUNKO ONO and HISAE YOSHIMURA Central Clinical Laboratory, Fukuoka University Hospital SATOSHI ICHIYAMA and SHIGETAKA MAEDA Department of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine YOICHI HIRAKATA and JUNICHI MATSUDA Department of Laboratory Medicine, Nagasaki University School of Medicine KIYOHARU YAMANAKA and YOKO MURATA Division of Clinical Laboratory, Ohtemae Hospital TETSUNORI SAIKAWA and KAZUFUMI HIRAMATSU Clinical Laboratory Center, Oita Medical University Hospital The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 899 strains of Gram-positive bacteria, 1500 strains of Gram-negative bacteria, and 158 strains of anaerobic

104(104) THE JAPANESE JOURNAL OF ANTIBIOTICS 57 1 Feb. bacteria obtained from 28 medical institutions during 2002 was measured. The results were as follows; 1. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MIC 90 of MEPM against Pseudomonas aeruginosa was the lowest of the drugs tested. MEPM showed low cross-resistant rate against both imipenem-resistant P. aeruginosa and ciprofloxacin-resistant P. aeruginosa. MEPM was active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE). 2. The proportion of extended-spectrum b -lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli and 1.9% (2 strains) in Klebsiella pneumoniae. Carbapenems including MEPM were active against these ESBL strains. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 7 years after available for commercial use.