1、Bacterial Resistance in China,Minggui Wang, M.D.Institute of Antibiotics Huashan Hospital, Fudan University,Outline,Antimicrobial Resistance and Its Mechanisms Gram-positive cocci Streptococcus pneumoniae Staphylococcus spp. Gram-negative bacilli Enterobacteriaceae Escherichia coli Klebsiella spp. E
2、nterobacter spp., et al. Non-fermenting gram-negative bacilli (non-fermenters),Antimicrobial Resistance in Streptococcus pneumoniae,History of studies on antimicrobial resistance on Streptococcus pneumoniae,1967 1970 1978 1980 1991 2001,-lactams (penicillin) Macrolides Fluoroquinolones,Penicillin re
3、sistance in S. pneumoniae in China in late 1990,PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae,* AAC 1998; 42: 2633,Penicillin resistance in S. pneumoniae in China in early 2000,PNSSP, penicillin non-susceptible
4、S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae,Penicillin resistance in S. pneumoniae has been increasing markedly since 2000,Increasing trends of Penicillin resistance in S. pneumoniae in China,Shanghai 100 strains each year,Beijing More than 10
5、0 strains each year,Clinical strains isolated from Childrens Hospital,Reasons causing the rapid increasing of penicillin resistance,The increasing consumption of oral penicillins such as amoxicillinThe spead of resistant colonines,Difference of penicillin resistance in S. pneumoniae isolated between
6、 adults and children,PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae,The penicillin resistance rates were much higher in children than that in adults,Resistance of S. pneumoniae to macrolides,70%-90% of S. pneumon
7、iae clinical isolates were resistant to erythromycin,Antimicrobial resistance of S. pneumoniae isolated from children in Beijing, Shanghai, Guangzhou and Xian（20002001）,Mechanism of bacterial resistance: Mosaic PBP Genes in PRSP,Penicillin resistance is due to alterations in endogenous PBPs DNA from
8、 related streptococci taken up and incorporated into S. pneumoniae genes,Mechanisms of resistance to macrolides (Wang M. Diagn Microbial Infect Dis 2001; 39:187),Target modification Phenotype cMLS, 90% (159/176) Phenotype iMLS, 6% (10/176)Active efflux Phenotype M 4% (7/176),Antimicrobial Resistance
9、 in Staphylococcus spp.,Trends of methicillin resistant Staphylococcus spp. (MRS) in China,5%-24%,35%-60%,50%-70%,Mechanism of MRSA,MRSA contain novel PBP2a, substitutes for native PBPs; low affinity for all -lactamsPBP2a is encoded by mecA gene; expression controlled by mecI, mecR1 and other factor
10、s,Summary Antimicrobial resistance in gram-positive cocci,Penicillin resistance in S. pneumoniae has been increasing markedly since 2000 in China The resistance rates of S. pneumoniae to macrolides such as erythromycin are very high Methicillin-resistant staphylococci are highly prevalent,Antimicrob
11、ial Resistance in Enterobacteriaceae,Antimicrobial resistance rates of E. coli isolated in China in 2005 (n=3758),Wang F. Chin J Infect Chemother 2006; 6: 289,Antimicrobial resistance rates of K. pneumoniae in China in 2005 (n=2234),Wang F. Chin J Infect Chemother 2006; 6: 289,Extended-spectrum -lac
12、tamases (ESBLs) in Enterobacteriaceae in China,ESBL-producing strains Hospital-acquired infections1: E. coli, 11-47% K. pneumoniae, 14-51% Community-acquired infections2: E. coli, 16% K. pneumoniae, 17% The main genotype of ESBLs is CTX-M1, typically provides resistance to ceftaxime but often not to
13、 ceftazidime or aztreonam3,1, Xiong Z. Diagn Microbiol Infect Dis 2002; 44: 195 2, Ling TK. AAC 2006; 50: 374 3, Jacoby GA. Chin J Infect Chemother 2006; 6: 361,Quinolone resistance rates in clinical isolates of E. coli in Shanghai,Mechanisms involved in quinolone resistance,Alterations in drug targ
14、et enzymes (DNA gyrase and/or topoisomerase IV) Alterations in drug accumulation (active efflux system)Both result from chromosomal mutations,Target modification,Efflux,Plasmid-mediated quinolone resistance: qnr determinats,qnr,qnrA: Lancet, 1998, the U.S. qnrB: AAC, 2006, the U. S. qnrS: AAC, 2005,
15、 Japan qnrC: 7th NCCM, 2007, China,Plasmid-mediated quinolone resistance,qnr family: qnrA, qnrB, qnrS, qnrCProtection of quinolone targets aac(6)-Ib-cr (2006)aminoglycoside acetyltransferase qepA (2007)quinolone efflux pump,Summary Antimicrobial resistance in gram-negative bacilli,ESBLs-producing st
16、rains of E. coli and K. pneumoniae are common, and spreading from hospital to community Quinolone resistance rates in E. coli are especially high New mechanisms of plasmid-mediated quinolone resistance emerged,Antimicrobial Resistance in Non-fermenting gram-negative bacilli (non-fermenters),Importan
17、ce of non-fermenters,Non-fermenting gram-negative bacilli (non-fermenters) include: Pseudomonas aeruginosa Acinetobacter spp. Stenotrophomonas maltophilia Alcaligenes spp. Burkholderia spp Flavobacterium (Chryseobaterium) spp. , et al Non-fermenters are highly resistant to commonly used antimicrobia
18、ls The infections of non-fermenters are difficult to treat with high mortality,Percentage of non-fermenters in gram-negative bacilli in Shanghai hospitals (Wang F, et al. Int J Antimicrob Agents 2003; 22: 444),Year,No of strains,High incidence of non-fermenters in Gram-negative bacilli,45% (6686/152
19、44) of GNB were non-fermenters in CHINET (Resistance surveillance network in China) surveillance program in China in 2005 (Wang F. Chin J Infect Chemother 2006; 6: 289) Non-fermenters increased from 41% in 1999 to 48% in 2001 in ICU clinical isolates of GNB in NPRS (Nosocomial Pathogens Resistance S
20、urveillance) study program in China(Wang H, Chen MJ. Natl Med J China 2003; 83:385),Resistance profile of 6123 strains of non-fermenters against 8 antimicrobials in CHINET in 2005 (Wang F. Chin J Infect Chemother 2006; 6:289 ),Trends in antimicrobial resistance rates among strains of P. aeruginosa i
21、solated from Shanghai hospitals(%),* Testing year, number of isolates in the parentheses,Mechanisms of resistance to imipenem in P. aeruginosa,Producing of -lactamases:carbapenemases IMP, VIM, OXA, KPC, GIM, SPM families ESBLs AmpC Decreased permeability: lost of porin D2 Active efflux,Trends in ant
22、imicrobial resistance rates among strains of Acinetobacter spp. isolated from Shanghai hospitals(%),* Testing year, number of isolates in the parentheses,Antimicrobial resistance rates among ICU strains of Acinetobacter spp. in China between 2003 and 2004(%) (Wang H, et al. Chin J Lab Med 2005; 28:
23、1295),Outbreak of carbapenem-resistant A. baumannii in Beijing and Guangzhou (Wang H, et al. Chin J Lab Med 2005; 28: 636),MDR-AB, resistant to 3 of the following 5 drugs: Pip/TAZ, CAZ, Sul/CFP, Gen, Cip, Imi5% in 1995 67% in 2002 in BJ20% in 1998 57% in 2002 in GZ 90%(35/39) strains produced OXA-23
24、 carbapenemase PFGE results indicated resistance colonies spread in each of 4 hospitals, mainly in patients with VAP and surgical infections,Lane 1-3, 5, 8, 11-16 PFGE type A, indicating same colony,Outbreak of COS-AB in Shanghai (Yang L, et al. Natl Med J China 2006; 86: 592),Outbreak of COS-AB (co
25、listin-only-sensitive A. baumannii) in some hospitals PFGE type B strains caused outbreak of COS-AB in burn ward in a Shanghai hospital PFGE type A strains of COS-AB spread in surgical wards,Lane 5-10, 13-14, PFGE type ALane 3-4, 12, PFGE type B,Trends in antimicrobial resistance rates among strains
26、 of S. maltophilia isolated from Shanghai hospitals(%),Summary Antimicrobial resistance in non-fermenters,The isolation of non-fermenters has been increasing in recent years The resistance rates of non-fermenters have been increasing More than 20% strains of P. aeruginosa are resistant to imipenem T
27、here were reports of outbreak of carbapenem-resistant A. baumannii,Conclusions,Antimicrobial resistance becomes a big problem in the field of Infectious Diseases in China Rational use of antimicrobials is the most important way to decrease or hinder antimicrobial resistance,Huashan Hospital, Bird View,THANK YOU,
