中国细菌耐药现状

• Non-fermenting gram-negative bacilli (non-fermenters)
Antimicrobial Resistance in Streptococcus pneumoniae
History of studies on antimicrobial resistance on Streptococcus pneumoniae
• DNA from related streptococci taken up and incorporated into S. pneumoniae genes
S SXN
PBP 2b
Czechoslovakia (1987)
South Africa (1978) USA (1983)
pen-sensitive S. pneumoniae
l l z me em in me in Su Su Ta in ac SM e m n im ne pi ll ll xi p/ P/ p/ en ci id pe fe ip xa ci ci ta Am CF Pi az ro Ce Im lo pi ra fo Am ik ZTM P
ft
Me Ci
First case of PRSP
Penicillin resistance in S. pneumoniae in China in late 1990’
Year Region Populati on Adults Source Clinical Clinical Carriage Clinical
1967 1970 1978 1980 1991
Global problem
2001
Regional problem
Spread around the world β-lactams (penicillin) Mechanism of PRSP First case of MDR Macrolides Fluoroquinolones

Active efflux
• Phenotype M 4% (7/176)
Antimicrobial Resistance in Staphylococcus spp.
Trends of methicillin resistant Staphylococcus spp. (MRS) in China
68 60
3 13
3 13
0 0
34
124 69
9
7Βιβλιοθήκη Baidu 20
9
42 17
0
28 3
PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae
Am
pe
Ce
Ce
Pi
Wang F. Chin J Infect Chemother 2006; 6: 289
pr
of
Antimicrobial resistance rates of K. pneumoniae in China in 2005 (n=2234)
100 90 80 70 60 50 40 30 20 10 0
Streptococcus ?
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)
2000
2001
2002
2002
2003
2004
Shanghai
100 strains each year
Beijing
More than 100 strains each year
Clinical strains isolated from Children’s Hospital
Reasons causing the rapid increasing of penicillin resistance
Ce f ur ox
Ce ftr i ax
Am ox
Ce f ac
r om yc
Er yth
Te
tra c
yc lin
on
e
v
Mechanism of bacterial resistance: Mosaic PBP Genes in PRSP

Penicillin resistance is due to alterations in endogenous PBPs
l l z me em in me in Su Su Ta in ac SM e m n im ne pi ll ll xi p/ P/ p/ en ci id pe fe ip xa ci ci ta Am CF Pi az ro Ce Im lo pi ra fo Am ik ZTM P
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Me Ci
Clinical
151
79 244 553
15
14 14 14
*
15
11 13 12
0
2 1 2
1997* 99-00
Children
Carriage Clinical
PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae
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
Resistance of S. pneumoniae to macrolides
70%-90% of S. pneumoniae clinical isolates were resistant to erythromycin
Antimicrobial resistance of S. pneumoniae isolated from children in Beijing, Shanghai, Guangzhou and Xi’an（2000－2001）
Am
pe
Ce
Ce
Pi
Wang F. Chin J Infect Chemother 2006; 6: 289
The penicillin resistance rates were much higher in children than that in adults
Year Region Populati on Adults 96-99 Shanghai Children Adults 2004 Shanghai Children 2004 Multiple centers Adults Clinical Clinical Clinical Clinical Source Clinical No. of Strains PNSSP (%) PISP (%) PRSP (%)
Antimicrobial Resistance in Enterobacteriaceae
Antimicrobial resistance rates of E. coli isolated in China in 2005 (n=3758)
90 80 70 60 50 40 30 20 10 0
Guangzhou
No. of Strains
PNSSP (%)
PISP (%)
PRSP (%)
68 60
3 13
3 13
0 0
96-99
1998 1998
Shanghai
Children Children
222
102
14
12
14
12
0
0
Children
Bejing 4 centers
Carriage
55 43 40 41
49 32 34 37
6 11 6 4
3 centers
Children
Clinical
00-01
4 centers
Children
Clinical
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’
Penicillin resistance in S. pneumoniae has been increasing markedly since 2000
Increasing trends of Penicillin
resistance in S. pneumoniae in China
70 60 50 40 1 30 49 20 10 0 34.7 50 6 11
70 60 50
R I
40 5 30 2 20 10 0 23 25 31 0
R I

The increasing consumption of oral penicillins such as amoxicillin
The spead of resistant colonines

Difference of penicillin resistance in S. pneumoniae isolated between adults and children
100 90 80 70 60 50 40 30 20 10 0
nic i Pe
4 0 0.06
84
82
76
0
R I
37 1
7
14
11
15
7 10 7 7
40
0
49
in
TM PSM Z Ch l or am ph en ico l Cip rof lox ac in
im e
llin
e
/C la
lor
• Streptococcus pneumoniae • Staphylococcus spp.

Gram-negative bacilli
• Enterobacteriaceae

Escherichia coli Klebsiella spp. Enterobacter spp., et al.
Year 2001 01-02 00-02 Region Shanghai
Beijing Shenyang
Populati on Children
Source Clinical Clinical
No. of Strains
PNSSP (%)
PISP (%)
PRSP (%)
100 192 887 624
50%-70%
60 50 40 30 20 10 0 1980's 1990's 2000'
35%-60%
5%-24%
Mechanism of MRSA

MRSA contain novel PBP2a, substitutes for native PBPs; low affinity for all -lactams PBP2a is encoded by mecA gene; expression controlled by mecI, mecR1 and other factors

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