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Bacterial Resistance in China

Bacterial Resistance in China. Minggui Wang, M.D. Institute of Antibiotics Huashan Hospital, Fudan University. Outline. Antimicrobial Resistance and It’s Mechanisms Gram-positive cocci Streptococcus pneumoniae Staphylococcus spp. Gram-negative bacilli Enterobacteriaceae Escherichia coli

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Bacterial Resistance in China

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  1. Bacterial Resistance in China Minggui Wang, M.D. Institute of Antibiotics Huashan Hospital, Fudan University

  2. Outline Antimicrobial Resistance and It’s Mechanisms • Gram-positive cocci • Streptococcus pneumoniae • Staphylococcus spp. • Gram-negative bacilli • Enterobacteriaceae • Escherichia coli • Klebsiella spp. • Enterobacter spp., et al. • Non-fermenting gram-negative bacilli (non-fermenters)

  3. Antimicrobial Resistance in Streptococcus pneumoniae

  4. Global problem Regional problem Spread around the world Mechanism ofPRSP First case of MDR First case of PRSP History of studies on antimicrobial resistance on Streptococcus pneumoniae 1967 1970 1978 1980 1991 2001 β-lactams (penicillin) Macrolides Fluoroquinolones

  5. Penicillin resistance 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

  6. Penicillin resistance in S. pneumoniae in China in early 2000’ Penicillin resistance in S. pneumoniae has been increasing markedly since 2000 PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae

  7. Increasing trends ofPenicillin resistance in S. pneumoniae in China Shanghai 100 strains each year Beijing More than 100 strains each year Clinical strains isolated from Children’s Hospital

  8. Reasons causing the rapid increasing of penicillin resistance • The increasing consumption of oral penicillins such as amoxicillin • The spead of resistant colonines

  9. Difference of penicillin resistance in S. pneumoniae isolated between adults and children The penicillin resistance rates were much higher in children than that in adults PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae

  10. Resistance of S. pneumoniae to macrolides 70%-90% of S. pneumoniae clinical isolates were resistant to erythromycin

  11. Antimicrobial resistance ofS. pneumoniaeisolated from children in Beijing, Shanghai, Guangzhou and Xi’an（2000－2001）

  12. S SXN PBP 2b Czechoslovakia (1987) South Africa (1978) USA (1983) pen-sensitive S. pneumoniae Streptococcus ? Mechanism of bacterial resistance:Mosaic PBP Genes in PRSP • Penicillin resistance is due to alterations in endogenous PBPs • DNA from related streptococci taken up and incorporated into S. pneumoniae genes

  13. 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)

  14. Antimicrobial Resistance in Staphylococcus spp.

  15. Trends of methicillin resistant Staphylococcus spp. (MRS) in China 50%-70% 35%-60% 5%-24%

  16. Mechanism of MRSA • MRSA contain novel PBP2a, substitutes for native PBPs; low affinity for all -lactams • PBP2a is encoded by mecAgene; expression controlled by mecI, mecR1 and other factors

  17. SummaryAntimicrobial 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

  18. Antimicrobial Resistance in Enterobacteriaceae

  19. Antimicrobial resistance rates of E. coli isolated in China in 2005 (n=3758) Wang F. Chin J Infect Chemother 2006; 6: 289

  20. Antimicrobial resistance rates of K. pneumoniae in China in 2005 (n=2234) Wang F. Chin J Infect Chemother 2006; 6: 289

  21. Extended-spectrum β-lactamases (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 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

  22. Quinolone resistance rates in clinical isolates of E. coli in Shanghai

  23. Mechanisms involved in quinolone resistance • Alterations in drug target enzymes (DNA gyrase and/or topoisomerase IV) • Alterations in drug accumulation (active efflux system) Both result from chromosomal mutations Efflux Target modification

  24. Conjugation R R S R Transformation S R R Plasmid-mediated quinolone resistance: qnr determinats qnr qnrA: Lancet, 1998, the U.S. qnrB: AAC, 2006, the U. S. qnrS: AAC, 2005, Japan qnrC: 7th NCCM, 2007, China

  25. Plasmid-mediated quinolone resistance • qnr family: qnrA, qnrB, qnrS, qnrC Protection of quinolone targets • aac(6’)-Ib-cr (2006) aminoglycoside acetyltransferase • qepA (2007) quinolone efflux pump

  26. SummaryAntimicrobial resistance in gram-negative bacilli • ESBLs-producing strains 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

  27. Antimicrobial Resistance in Non-fermenting gram-negative bacilli (non-fermenters)

  28. Importance 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 antimicrobials • The infections of non-fermenters are difficult to treat with high mortality

  29. 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

  30. High incidence of non-fermenters in Gram-negative bacilli • 45% (6686/15244) 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 Surveillance) study program in China (Wang H, Chen MJ. Natl Med J China 2003; 83:385)

  31. Resistance profile of 6123 strains of non-fermenters against 8 antimicrobials in CHINET in 2005 (Wang F. Chin J Infect Chemother 2006; 6:289 )

  32. Trends in antimicrobial resistance rates among strains of P. aeruginosa isolated from Shanghai hospitals(%) * Testing year, number of isolates in the parentheses

  33. Decreased permeability Inactivation Efflux X Mechanisms of resistance to imipenem in P. aeruginosa • Producing of β-lactamases: • carbapenemases • IMP, VIM, OXA, KPC, GIM, SPM families • ESBLs • AmpC • Decreased permeability: lost of porin D2 • Active efflux

  34. Trends in antimicrobial resistance rates among strains of Acinetobacter spp. isolated from Shanghai hospitals(%) * Testing year, number of isolates in the parentheses

  35. 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: 1295)

  36. 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, Imi 5% in 1995 → 67% in 2002 in BJ 20% in 1998 → 57% in 2002 in GZ • 90%(35/39) strains produced OXA-23 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

  37. Outbreak of COS-AB in Shanghai(Yang L, et al. Natl Med J China 2006; 86: 592) • Outbreak of COS-AB (colistin-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 A Lane 3-4, 12, PFGE type B

  38. Trends in antimicrobial resistance rates among strains of S. maltophilia isolated from Shanghai hospitals(%)

  39. SummaryAntimicrobial 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 • There were reports of outbreak of carbapenem-resistant A. baumannii

  40. 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

  41. Huashan Hospital, Bird View THANK YOU

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