上海地区肠杆菌科细菌产超广谱β内酰胺酶情况及药敏监测
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摘要
【目的］了解上海地区肠杆菌科细菌产超广谱β-内酞胺酶
（ESBLs）情况；了解产ESBLs菌对11种常见抗生素的耐药情
况；比较并评价双纸片协同扩散法、Etest法和双纸片增效法对
ESBLs的检出率。
[方法] 收集 1999年 3月～1999年 10月上海地区 4家医院
分离的肠杆菌科细菌 1026株，用Kirby-Bauer法作药敏试验；用
双纸片协同扩散法检测ESBLs；分别用双纸片协同扩散法、Etest
法和双纸片增效法三种方法对10株参考产ESBLs菌株与200株
临床肺炎克雷伯杆菌和大肠埃希菌菌株检测ESBLs。
[结果] 常规药敏试验结果显示，在 11种抗生素中耐药率最
低的是亚胺培南（0．10％）和头孢美唑（13．84％） 耐药率最高的
是环丙沙星（47．56％）和头孢呋新（43．96％） 其中环丙沙星对大
肠埃希菌的耐药率高达68．88％；除头孢他啶外，其它第三代头
孢菌素和氨曲南的耐药率均在 30％以上，高于阿米卡星的耐药率
（2．26％）；在所有肠杆菌科细菌中，阴沟肠杆菌的耐药问题尤
为严重，仅亚胺培南和阿米卡星敏感性较好，分别为 100％和
70．91％。在 1026株肠杆菌科细菌中，用双纸片协同扩散法共检
出产ESBLs菌352株，检出率为34．31％，其中肺炎克雷伯杆菌
为37．40％，大肠埃希菌为30．21％,阴沟肠杆菌为41．82％，产气
肠杆菌和枸橼酸杆菌也分别检测到产ESBLs菌；各种来源标本
上躇站互厂方亦杆勿q产走广办p－o 份况和矽仪士肘－
肠杆茵科细菌产ESBLs率无显著差异，各种杭生素纸片对ESBLs
的检出率也无显著差异；除亚胺培南和头抱美哇外，产ESBLs
菌对其它 9种抗生素的耐药率显著高于非产 ESBLs菌（P＜0．of），
亚胺培南和头抱美哇对产 ESBLS菌的敏感性最高，分别为 100O
和 84．66o。在 10株参考产 ESBLs菌株中，用双纸片协同扩散法、
Etest法和双纸片增效法三种方法分别检出 9株、9株和 10株，
检出率分别为 90％、90％和 100％。i种方法对 200株临床菌株
中产ESBLs菌的检出率分别为刀％、75％和79％，三种方法间
无显著差异。
l结论］上海地区肠杆菌科细菌中产 ESBLs菌流行情况严
重，上海地区临床实验室有必要常规检测肠杆菌科细菌是否产
田＊L引 上海地区肠杆菌科细菌耐药问题严重，产田＊k菌对大
多数抗生素的耐药性比非产ESBLs菌严重得多，亚胺培南和头
袍美哩是治疗由产ESBLs菌引起感染的有效抗生素；双纸片协
同扩散法和双纸片增效法敏感性高、经济、操作简便易行，适宜
在各级医院临床实验室推广普及。
[Objectives] To investigate extended-spectrum beta-
lactamases(ESBLs) production in clinical isolates of the family
Enterobacteriaceae in Shanghai and the resistant rates of ESBLs-
producing strains to antibiotics; To evaluate the isolating rates of
ESBLs by double-disk synergy test, Etest and inhibitor-potentiated
disk-diffusion test respectively.
[Methods] 1026 clinical isolates of the family
Enterobacteriaceae were collected from 4 hospitals in Shanghai from
March 1999 to October 1999. Kirby-Bauer method was used to judge
drug sensitivity; Double-disk synergy test was used to detect ESBLs.
Double-disk synergy test, Etest and inhibitor-potentiated disk-
diffusion test were used to detect ESBLs in 10 reference strains and
200 clinical isolates of Klebsiella pneumoniae and Escherichia coli
respectively.
[Resultu] In 11 antibiotics, Imipenem and Cefmetazole had the
lowest resistant rates of 0.10% and 13.84% respectively, while
Ciprofloxacin and Cefuroxime had the highest resistant rates of
47.56% and 43.96% respectively, and the resistant rate of Escherichia
coli strains to Ciprofloxacin was 68.88%; Except Ceflazidime, the
resistant rates of oxyimino-lactams and monobactatns were more
than 30%, which was higher than that of Amikacin(32.26%). In the
boly Enterobacrtceae, the resistance of Enterobacter clOacae
was especially serious, and only the sensforities of boenem and
Wacin were good, with the sensitive rates being l00% and 70.9l%
respectively In all l026 clforcal isolates of the family
Enterobacteriaceae, 352 stheins were considered ESBLs producers by
double-disk synergy test, with the isolatin rate being 34.3l%.
37.40%, 30.2l% and 41.82% of strains of Klebsiella pneumonltre,
Eschwtia coll and Enterobacter cloacae resPectlyely were
considerd ESBLs producers. ESBLs was also detected in strains of
EnterObacter aerWes and Cbobacter hedi. There was no
evident difference in the isolating rates betWeen differen clforcal
sPecAnens, so was With difor antibiOtic disks. ExcePt bom
and Cefinerezole, the resishat rates of ESBLs-producing strains to
other 9 antibiotics were much higher than that of non-ESBLs-
produCing strains(P < 0.0l). The resistan rates of twenem and
Cebole to ESBLs-producing triins were the loweSt. In l0
reference strains, 9, 9 and l0 shas were considered ESBLs-
producing strains by double-disk Synergy tCst, Etest, inhiitOr
potentiated disk-ditheion test resPectively In 200 clforcal isolates of
Klebsiella pneumoniae and EscheriChia coli, 73%, 75% and 79%
were considered ESBLs producers with the three methods
respechvely which were not differen evidently
IConclusionsl The PrCvalence of ESBLs in clinical isolates of
the boly EnterObacrtceae in Shanghai was high, and it is
necessary for clforcal laboratory to deect ESBLs in clforcal isolates of
the family Enterobacteriaceae in routine. The resistan rates of
ESBLs-producing strains to most antibiotics were much higher than
tha of non-ESBLs-producing strains. Iwienem and CeAnetazole
were the effective anibiotics tO infections caused by ESBLs-
producing stheins. Double-disk synergy test and inhibitorTotentiated
disk-diffosion test are sutable for screening ndins producing ESBLs
in rouine in all hospitals.
（ESBLs）情况；了解产ESBLs菌对11种常见抗生素的耐药情
况；比较并评价双纸片协同扩散法、Etest法和双纸片增效法对
ESBLs的检出率。
[方法] 收集 1999年 3月～1999年 10月上海地区 4家医院
分离的肠杆菌科细菌 1026株，用Kirby-Bauer法作药敏试验；用
双纸片协同扩散法检测ESBLs；分别用双纸片协同扩散法、Etest
法和双纸片增效法三种方法对10株参考产ESBLs菌株与200株
临床肺炎克雷伯杆菌和大肠埃希菌菌株检测ESBLs。
[结果] 常规药敏试验结果显示，在 11种抗生素中耐药率最
低的是亚胺培南（0．10％）和头孢美唑（13．84％） 耐药率最高的
是环丙沙星（47．56％）和头孢呋新（43．96％） 其中环丙沙星对大
肠埃希菌的耐药率高达68．88％；除头孢他啶外，其它第三代头
孢菌素和氨曲南的耐药率均在 30％以上，高于阿米卡星的耐药率
（2．26％）；在所有肠杆菌科细菌中，阴沟肠杆菌的耐药问题尤
为严重，仅亚胺培南和阿米卡星敏感性较好，分别为 100％和
70．91％。在 1026株肠杆菌科细菌中，用双纸片协同扩散法共检
出产ESBLs菌352株，检出率为34．31％，其中肺炎克雷伯杆菌
为37．40％，大肠埃希菌为30．21％,阴沟肠杆菌为41．82％，产气
肠杆菌和枸橼酸杆菌也分别检测到产ESBLs菌；各种来源标本
上躇站互厂方亦杆勿q产走广办p－o 份况和矽仪士肘－
肠杆茵科细菌产ESBLs率无显著差异，各种杭生素纸片对ESBLs
的检出率也无显著差异；除亚胺培南和头抱美哇外，产ESBLs
菌对其它 9种抗生素的耐药率显著高于非产 ESBLs菌（P＜0．of），
亚胺培南和头抱美哇对产 ESBLS菌的敏感性最高，分别为 100O
和 84．66o。在 10株参考产 ESBLs菌株中，用双纸片协同扩散法、
Etest法和双纸片增效法三种方法分别检出 9株、9株和 10株，
检出率分别为 90％、90％和 100％。i种方法对 200株临床菌株
中产ESBLs菌的检出率分别为刀％、75％和79％，三种方法间
无显著差异。
l结论］上海地区肠杆菌科细菌中产 ESBLs菌流行情况严
重，上海地区临床实验室有必要常规检测肠杆菌科细菌是否产
田＊L引 上海地区肠杆菌科细菌耐药问题严重，产田＊k菌对大
多数抗生素的耐药性比非产ESBLs菌严重得多，亚胺培南和头
袍美哩是治疗由产ESBLs菌引起感染的有效抗生素；双纸片协
同扩散法和双纸片增效法敏感性高、经济、操作简便易行，适宜
在各级医院临床实验室推广普及。
[Objectives] To investigate extended-spectrum beta-
lactamases(ESBLs) production in clinical isolates of the family
Enterobacteriaceae in Shanghai and the resistant rates of ESBLs-
producing strains to antibiotics; To evaluate the isolating rates of
ESBLs by double-disk synergy test, Etest and inhibitor-potentiated
disk-diffusion test respectively.
[Methods] 1026 clinical isolates of the family
Enterobacteriaceae were collected from 4 hospitals in Shanghai from
March 1999 to October 1999. Kirby-Bauer method was used to judge
drug sensitivity; Double-disk synergy test was used to detect ESBLs.
Double-disk synergy test, Etest and inhibitor-potentiated disk-
diffusion test were used to detect ESBLs in 10 reference strains and
200 clinical isolates of Klebsiella pneumoniae and Escherichia coli
respectively.
[Resultu] In 11 antibiotics, Imipenem and Cefmetazole had the
lowest resistant rates of 0.10% and 13.84% respectively, while
Ciprofloxacin and Cefuroxime had the highest resistant rates of
47.56% and 43.96% respectively, and the resistant rate of Escherichia
coli strains to Ciprofloxacin was 68.88%; Except Ceflazidime, the
resistant rates of oxyimino-lactams and monobactatns were more
than 30%, which was higher than that of Amikacin(32.26%). In the
boly Enterobacrtceae, the resistance of Enterobacter clOacae
was especially serious, and only the sensforities of boenem and
Wacin were good, with the sensitive rates being l00% and 70.9l%
respectively In all l026 clforcal isolates of the family
Enterobacteriaceae, 352 stheins were considered ESBLs producers by
double-disk synergy test, with the isolatin rate being 34.3l%.
37.40%, 30.2l% and 41.82% of strains of Klebsiella pneumonltre,
Eschwtia coll and Enterobacter cloacae resPectlyely were
considerd ESBLs producers. ESBLs was also detected in strains of
EnterObacter aerWes and Cbobacter hedi. There was no
evident difference in the isolating rates betWeen differen clforcal
sPecAnens, so was With difor antibiOtic disks. ExcePt bom
and Cefinerezole, the resishat rates of ESBLs-producing strains to
other 9 antibiotics were much higher than that of non-ESBLs-
produCing strains(P < 0.0l). The resistan rates of twenem and
Cebole to ESBLs-producing triins were the loweSt. In l0
reference strains, 9, 9 and l0 shas were considered ESBLs-
producing strains by double-disk Synergy tCst, Etest, inhiitOr
potentiated disk-ditheion test resPectively In 200 clforcal isolates of
Klebsiella pneumoniae and EscheriChia coli, 73%, 75% and 79%
were considered ESBLs producers with the three methods
respechvely which were not differen evidently
IConclusionsl The PrCvalence of ESBLs in clinical isolates of
the boly EnterObacrtceae in Shanghai was high, and it is
necessary for clforcal laboratory to deect ESBLs in clforcal isolates of
the family Enterobacteriaceae in routine. The resistan rates of
ESBLs-producing strains to most antibiotics were much higher than
tha of non-ESBLs-producing strains. Iwienem and CeAnetazole
were the effective anibiotics tO infections caused by ESBLs-
producing stheins. Double-disk synergy test and inhibitorTotentiated
disk-diffosion test are sutable for screening ndins producing ESBLs
in rouine in all hospitals.
引文
1. karkainen, Ikaheimo R, Katila ML, et al. P fimbriation of escherichia coli strains from patients with urosepsis demonstrated by a commercial agglutinations test. J Clin Microbiol, 1991, 29: 221-225.
2. Sader HS, Pfaller MA, Jones RN. Prevalence of important pathogens and the antimicrobiol activity of parenteral drags at numerous medical centers in the United States. Diagn Microbiol Infect Dis, 1994, 20: 203-208.
3．王露霞，徐德兴，刘刃等．革兰阴性杆菌超广谱酶、诱导酶及药敏检测结果．中华医院感染学杂志，1998，8：52-54．
4．徐英春，谢秀丽，刘刃等．3236株细菌对头孢美唑和其他10种β-内酰胺药敏感性分析．中华医学检验杂志，1998，21：104-105．
5. Philippon A, Ben RS, Fournier G, et al. Epidemiology of extended-spectrum beta-lactamases. Infection, 1989, 17: 347-354.
6. Knothe H, Shah P, Kremery V, et al. Transferable resistance to Cefotaxime, Cefoxitin, Cefamandole and Cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection, 1983, 11:315-317.
7. Jacoby GA, Medeiros AA. More extended-spectrum betalactamases. Antimicrob Agents Chemother, 1991, 35:1697-1704.
8. Christopher LE, Lisa AW. Detection and clinical significance of extended-spectrum β-lactamases in a tertiary-care medical center. J Clin Microbiol, 1997, 35: 2061-2067.
9. Yuan M, Aucken H, Hall LM, et al. Epidemiological typing of Klebsiellae with extended-spectrum beta-lactamases from
European intensive care units. J Antimicrob Chemother, 1998, 41:527-539.
10. Pai H. The characteristics of extended-spectrum beta-lactamases in Korean isolates of Enterobacteriaceae. Yonsei Med J. 1998, 39: 514-519.
11. Sader HS, Jones RN, Gales AC, et al. Antimicrobial susceptibility patterns for pathogens isolates from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surreillance program(1997). SENTRY Latin American Study Group. Diagn Microbiol Infect Dis, 1998, 32: 289-301.
12. Bou G, Martinez BJ, Cervero G, et al. Biochemical and genetic characteristics of TEM-29B, a novel extended-spectrum betalactamase. FEMS Microbiol Lett, 1999, 174: 185-190.
13．王辉，谢秀丽，徐英春等．革兰阴性杆菌对12种抗生素的耐药监测-Etest法．中华医学检验杂志，1997，20：265-269．
14．熊剑辉．Etest用于革兰阴性杆菌超广谱β-内酰胺酶测定．临床检验杂志，1998，16：138-140．
15．孙长贵，陈汉美，颜秉兴等．评价三种筛选方法检测超广谱β-内酰胺酶及其临床应用．中华医学检验杂志，1999，22：228-231．
16. Blahova J, Lesicka HM, Kralikova K, et al. Further occurrence of extended-spectrum beta-lactamase-producing Salmonella enteritidis. J Chemother. 1998, 10: 291-294.
17. Vercauteren E, Descheemaeker P, Ieven M, et al. Comparison of screening methods for detection of extended-spectrum β-lactamases and their prevalence among blood isolates of Escherichia coli and klebsiella spp. in a Belgian teaching hospital. J Clin Microbial, 1997, 35: 2191-2197.
18． Katsanis GP, Spargo J, Ferraro MJ, et al. Detection of klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum β-lactamases. J Clin Microbiol, 1994,32: 691-696．
19． Prodinger WM, File M, Bauernfeind A, et al. Molecular epidemiology of klebsiella pneumoniae producing SHV-5 β-lactamases: parallel outbreaks due to multiple plasmid transfer. J Clin Microbial, 1996, 34: 564-570．
20． Jacoby GA, Carreras I. Activities of β-lactam antibiotics against Escherichia coli strains producing extended-spectrum β-lactamases. Antimicrob Agents Chemother, 1990, 34: 858-862．
21． Jan IS, Hsueh PR, Teng LT, et al. Antimicrobial susceptibility testing for Klebsiella pneumoniae isolates resistant to extended-spectrum beta-lactam antibiotics. J Formos Med Assoc, 1998, 91: 661-666．
22． Philippon A, Paul G, Vedel G, et al. Resistance plasmidique aux cephalosporines de 3e generation. Presse Med. 1988, 17: 1883-1889．
23． Sirot J, Chanal C, Petit A, et al. Klebsiella pneumoniae and other Enterobacteriaceae producing novel plasmid-mediated β-lactamases markedly active against third-generation cephalosporins: epidemiologic studies. Rev Infect Dis, 1988, 10: 850-859．
24． Thomson KS, Sanders CC. Detection of extended-spectrum β-lactamases in members of the family Enterobacteriaceae: comparison of double-disk and three-dimensional tests. Antimicrob Agents Chemother, 1992, 36: 1877-1882．
25． Rice LB, Willey SH, Papanicolaou GA, et al. Outbreak of Ceftazidime resistance caused by extended-spectrum β-
lactamases at a Massachusetts chronic-care facility. Antimicrob Agents Chemother, 1990,34: 2194-2199．
26． Smith CE, Tillman BS, Howell AW, et al. Failure of Ceftazidime-Amikacin theropy for bacteremia and meningitis due to klebsiella pneumoniae producing an extended-spectrum β-lactamase. Antimicrob Agents Chemother, 1990, 34:2190-2193．
27． Fantin B, Pangon B, Potel G, et al. Activity of sulbactam in combination with Ceftriaxone in Vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like β-lactamase. Antimicrob Agents Chemother, 1990,34:581-586．
28． Caron F, Gutmann L, Bure A, et al. Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 β-lactamase. Antimicrob Agents Chemother, 1990, 34:2070-2074．
29． Sanders CC, Barry AL, Washington JA, et al. Detection of extended-spectrum β-lactamases-producing members of the family Enterobacteriaceae with the Vitek ESBLs test. J Clin Microbiol, 1996, 34: 2997-3001．
30． Ho PL, Chow KH, Yuen KY, et al. Comparison of a novel, inhibitor-potentiated disk-diffusion test with other methods for the detection of extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae. J Antimicrob Chemother, 1998, 42: 49-54．
31． Cormican MG, Marshall SA, Jones RN. Detection of extended-spectrum β-lactamase(ESBLs)-producing strains by the Etest ESBLs screen. J Clin Microbial, 1996, 34: 1880-1884．
2. Sader HS, Pfaller MA, Jones RN. Prevalence of important pathogens and the antimicrobiol activity of parenteral drags at numerous medical centers in the United States. Diagn Microbiol Infect Dis, 1994, 20: 203-208.
3．王露霞，徐德兴，刘刃等．革兰阴性杆菌超广谱酶、诱导酶及药敏检测结果．中华医院感染学杂志，1998，8：52-54．
4．徐英春，谢秀丽，刘刃等．3236株细菌对头孢美唑和其他10种β-内酰胺药敏感性分析．中华医学检验杂志，1998，21：104-105．
5. Philippon A, Ben RS, Fournier G, et al. Epidemiology of extended-spectrum beta-lactamases. Infection, 1989, 17: 347-354.
6. Knothe H, Shah P, Kremery V, et al. Transferable resistance to Cefotaxime, Cefoxitin, Cefamandole and Cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection, 1983, 11:315-317.
7. Jacoby GA, Medeiros AA. More extended-spectrum betalactamases. Antimicrob Agents Chemother, 1991, 35:1697-1704.
8. Christopher LE, Lisa AW. Detection and clinical significance of extended-spectrum β-lactamases in a tertiary-care medical center. J Clin Microbiol, 1997, 35: 2061-2067.
9. Yuan M, Aucken H, Hall LM, et al. Epidemiological typing of Klebsiellae with extended-spectrum beta-lactamases from
European intensive care units. J Antimicrob Chemother, 1998, 41:527-539.
10. Pai H. The characteristics of extended-spectrum beta-lactamases in Korean isolates of Enterobacteriaceae. Yonsei Med J. 1998, 39: 514-519.
11. Sader HS, Jones RN, Gales AC, et al. Antimicrobial susceptibility patterns for pathogens isolates from patients in Latin American medical centers with a diagnosis of pneumonia: analysis of results from the SENTRY Antimicrobial Surreillance program(1997). SENTRY Latin American Study Group. Diagn Microbiol Infect Dis, 1998, 32: 289-301.
12. Bou G, Martinez BJ, Cervero G, et al. Biochemical and genetic characteristics of TEM-29B, a novel extended-spectrum betalactamase. FEMS Microbiol Lett, 1999, 174: 185-190.
13．王辉，谢秀丽，徐英春等．革兰阴性杆菌对12种抗生素的耐药监测-Etest法．中华医学检验杂志，1997，20：265-269．
14．熊剑辉．Etest用于革兰阴性杆菌超广谱β-内酰胺酶测定．临床检验杂志，1998，16：138-140．
15．孙长贵，陈汉美，颜秉兴等．评价三种筛选方法检测超广谱β-内酰胺酶及其临床应用．中华医学检验杂志，1999，22：228-231．
16. Blahova J, Lesicka HM, Kralikova K, et al. Further occurrence of extended-spectrum beta-lactamase-producing Salmonella enteritidis. J Chemother. 1998, 10: 291-294.
17. Vercauteren E, Descheemaeker P, Ieven M, et al. Comparison of screening methods for detection of extended-spectrum β-lactamases and their prevalence among blood isolates of Escherichia coli and klebsiella spp. in a Belgian teaching hospital. J Clin Microbial, 1997, 35: 2191-2197.
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