MRSA PRSP BLNAR 40. Key words: antimicrobial resistance, respiratory tract infection, community-acquired infection MRSA (PC) (CP)

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1 MRSA PRSP BLNAR 40 Key words: antimicrobial resistance, respiratory tract infection, community-acquired infection ) MRSA ( ) TEL: FAX: ubukatak@lisci.kitasato-u.ac.jp ) (PC) (ML) (TC) (CP) 2) 15 1

2 76 1. A 1975 T12 emm12 macrolide tetracycline, chloramphenicol 4), 5) TEM b-lactamase 6) b mm 7) MIC BLNAR 2. b- 16 mm A (GAS) 1 GAS ML T-12 emm12 GAS ML TC CP 3) MRSA MRSA 1980 MRSA 8) meca 3 ML meca PBP2 9) 2

3 77 12) (GPC) GNB MRSA 1980 MRSA b- meca 10), 11) MRSA MIC 1970 (GNB) MIC PBP3 PBP1A 1B 4 MIC 4. PRSP MRSA ) PRSP b- PRSP 14), 15) 1993 PRSP 3 16) 4,

6 PBP PBP1A PBP2X 2A 2B 20) PBP1A 2B 2X 2A b- PBP1A, PBP2X, PBP2B 3 PBP 6.

4 78 5. PRSP penicillin G (n 4,255) b- 17) 2 mg/ml (PRSP) 0.063mg/ml (PSSP) NCCLS CLSI b- 1 PISP PSSP PCR genotype (g) 18) PCR 19) b- (PBP) 6 PBP PBP1A PBP2X 2A 2B 20) PBP1A 2B 2X 2A b- PBP1A, PBP2X, PBP2B 3 PBP 6. PBP1A PBP2X PBP2B b- b- (Ser) PBP PBP 6 PBP (Ser) PBP PCR PBP PCR MIC 90 3 MIC 21) PBP2X 22) ML erm(b) 4

5 BLNAR PBP3 BLNAR(Low-BLNAR) BLNAR ampicillin cefcapene 2006 (n 365) BLNAR PBP3 ML mef(a) EM CAM AZM 1 8 mg/ml ML 20 PRSP 16) (AWS) 23) 24) 5. BLNAR 5 10 b (Hib) NT MIC mutant selection window (MSW) mutant prevention concentration (MPC) 6. ML ML ML 5

telithromycin 23S rrna 30) PCR 9 31) 33) 10 20 PCR 75 32) PCR 11.

6 PCR PCR 3, azithromycin (n 380) erythromycin, clarithromycin, telithromycin 23S rrna 30) PCR 9 31) 33) PCR 75 32) PCR 11. macrolide AZM EM, CAM, TEL, JM ML MIC ML 23S rrna V ) ML 35) ML MINO ML 7. MRSA, PRSP, BLNAR, ML (i) PBP DNA (ii) (iii) 6

pneumoniae (vi) Legionella pneumophila lyta mip GAS 16S rrna 38) 10 2 12 (AdV)

7 81 36) b- ML 8. Real-time PCR 5 37) realtime PCR 12 (i) (ii) (iii) (iv)gas b (v) Chlamydophila pneumoniae (vi) Legionella pneumophila lyta mip GAS 16S rrna 38) (AdV) A B(Flu) RSV (PIV)1, 2, 3, (RV) (EV) (CoV) (hmpv) (HBoV) AdV HBoV RNA RNA cdna ) 12. real-time PCR 2 DNA/RNA 13. real-time PCR PCR 7

82 14. 9. 14 2001 1) 2004. 14: 1 23. 2) 1977 2 30: 1513 1520. 3) Ubukata, K., M. Konno, R. Fujii. 1975.

8 ) : ) : ) Ubukata, K., M. Konno, R. Fujii Transduction of drug resistance to tetracycline, chloramphenicol, macrolides, lincomycin, and clindamycin with phages induced from Streptococcus pyogenes. J. Antibioitics 28: ) Haemophilus influenzae 1 Chemotherapy 26: ) Chemotherapy 26: ) ampicillin Haemophilus influenzae Chemotherapy 26: ) Haemophilus influenzae 4 Chemotherapy 26: ) 1991.MRSA 9) Ubukata, K., N. Yamashita, M. Konno Occurrence of a b-lactam-inducible penicillinbinding protein in methicillin-resistant staphylococci. Antimicrob. Agents Chemother. 27: ) Matsuhashi, M., M. D. Song, F. Ishino, et al Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to b-lactam antibiotics in Staphylococcus aureus. J.Bacteriol. 167: ) Ubukata, K., R. Nonoguchi, M. Matsuhashi, et al Expression and inducibility in Staphylococcus aureus of the meca gene, which encodes a methicillin-resistant S. aurues-specific penicillin-binding protein. J. Bacteriol. 171:

9 83 12) b- MIC 47: ) b- 1 62: ) Appelbaum, P. C Streptococcus pneumoniae resistant to penicillin and chloramphenicol. Lancet ii: ) Klugman, K. P., H. J. Koornhof Drug resistance patterns and serogroups or serotypes of pneumococcal isolates from serebrospinal fluid or blood, J. Infect. Dis. 158: ) ) Ubukata, K., Y. Asahi, K. Okuzumi, et al Incidence of penicillin-resistant Streptococcus pneumoniae in Japan, J. Infect. Chemother. 2: ) Ubukata, K., T. Muraki, A. Igarashi, et al Identification of penicillin and other b-lactam resistance in Streptococcus pneumoniae by PCR. J. Infect. Chemother. 3: ) Nagai, K., Y. Shibasaki, K. Yamamoto, et al Evaluations of the primers for PCR to screen Streptococcus pneumoniae islates, b- lactam resistance and to detect common macrolide resistance determinants. J. Antimicrob. Chemother. 48: ) Kobayashi, R., M. Konomi, K. Hasegawa, et al In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillinnonsusceptible Streptococcus pneumoniae. Antimicrob. Agents Chemother. 49: ) Chiba, N., R. Kobayashi, K. Hasegawa, et al Antibiotic susceptibility according to genotype of penicillin-binding protein and macrolide resistance genes and serotype of Streptococcus pneumoniae isolates from community-acquired pneumonia in children. J. Antimicrob. Chemother. 56: ) Ubukata, K Problems associated with high prevalence of multidrug-resistant bacteria in patients with community-acquired infections. J. Infect. Chemother. 9: ) : ) Yokota, S., K. Sato, S. Yoshida, N. Fujii Molecular epidemiology of fluoroquinoloneresistant Streptococcus pneumoniae in Japan 78: ) Ubukata, K., Y. Shibasaki, K. Yamamoto, et al Association of amino acid substitution in penicillin-binding protein 3 with b-lactam resistance in b-lactamase-negative ampicillinresistant Haemophilus influenzae. Antimicrob. Agents Chemother. 45: ) Hasegawa, K., et al Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States. Microbial Drug Resistance 9: ) Hasegawa, K., N. Chiba, R. Kobayashi, et al Rapidly increasing prevalence of b- lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae type b in meningitis. Antimicrob. Agents Chemother. 48: ) Haemophilus influenzae : ) Hasegawa, K., R. Kobayashi, E. Nakayama, et al High prevalence of type b b- lactamase-nonproducing ampicillin-resistant Haemophilus influenzae in meningitis: the situation in Japan where Hib vaccine has not been introduced. J. Antimicrob. Chemother. 57: ) : ) Okazaki, N., M. Narita, S. Yamada, et al Characteristics of macrolide-resistant Mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro. Microbiol. Immunol. 45: ) Morozumi, M., K. Hasegawa, N. Chiba, et al Application of PCR for Mycoplasma pneumoniae detection in children with communityacquired pneumonia. J. Infect. Chemother. 10: ) Morozumi, M., A. Ito, S. Y. Murayama, et al Assessment of real-time PCR for diagnosis of Mycoplasma pneumoniae pneumonia in pediatric patients. Can. J. Microbiol. 52: ) 2005 PCR 21: ) Morozumi, M., K. Hasegawa, R. Kobayashi, et al Emergence of macrolides-resistant Mycoplasma pneumoniae with a 23S rrna gene mutation. Antimicrob. Agents Chemother. 49:

10 84 35) Morozumi, M., S. Iwata, K. Hasegawa, et al Increased macrolide resistance of Mycoplasma pneumoniae in pediatric patients with community-acquired pneumonia. Antimicrob. Agents Chemother. 52: ) : ) : ) Morozumi, M., E. Nakayama, S. Iwata, et al Simultaneous detection of pathogens in clinical samples from patients with community-acquired pneumonia by real-time PCR with pathogen-specific molecular beacon probes. J. Clin. Microbiol. 44: ) Nakayama, E., K. Hasegawa, M. Morozumi, et al Rapid optimization of antimicrobial chemotherapy given to pediatric patients with community-acquired pneumonia using PCR techniques with serology and standard culture. J. Infect. Chemother. 13: Fundamentals of Rapidly-progressing Antimicrobial Resistance in Bacterial Pathogens Causing Community-acquired Respiratory Tract Infections Kimiko Ubukata Laboratory of Molecular Epidemiology for Infectious Agents, Graduate School of Infection Control Sciences & Kitasato Institute for Life Sciences, Kitasato University This is a substantial revision of the content of the Chairperson s Lecture at the 19th Japanese Society for Clinical Microbiology and states the fundamentals of antimicrobial resistance of bacterial pathogens causing respiratory tract infections which has become or is becoming clinical problems in Japan. Going back to a series of researches which the author has been involved in over 40 years, it is emphasized that precise and quick identification of causative microorganisms in onset of diseases is most required at present in bacteriological examinations. Which technique our laboratory is using to try to measure such situation is also described in detail. In microbiological examinations, it is important to identify causative microorganisms quickly and report it to the side of clinical practice for selection of the most appropriate antibacterial drugs based upon the results. The author also states that this is the e#ective method not only for treatment but also for preventing development of resistant bacteria. 10

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