Risk factors for fluoroquinolone resistance in nosocomial Escherichia coli and Klebsiella pneumoniae infections

BACKGROUND: The incidence of fluoroquinolone (FQ) resistance has increased markedly in recent years. Even in the common nosocomial pathogens Escherichia coli and Klebsiella pneumoniae, in which the emergence of FQ resistance was believed to be unlikely, increasing resistance to these agents has been noted. Risk factors for FQ resistance in these pathogens remain unknown. Although FQs are important components of the present antimicrobial arsenal, their continued usefulness is threatened by rising FQ resistance. OBJECTIVE: To identify risk factors for nosocomial FQ resistance. METHODS: A case-control study of hospitalized patients with infections due to FQ-resistant and FQ-susceptible E coli and K pneumoniae occurring between January 1, 1998, and June 30, 1999. RESULTS: We included 123 patients with nosocomial FQ-resistant infections and 70 randomly selected patients with nosocomial FQ-susceptible infections. Independent risk factors (adjusted odds ratio [95% confidence interval]) for FQ resistance were (1) recent FQ use (5.25 [1.81-15.26]); (2) residence in a long-term care facility (3.65 [1.64-8.15]); (3) recent aminoglycoside use (8.86 [1.71-45.99]); and (4) older age (1.03 [1.01-1.06]). CONCLUSIONS: Recent FQ use, residence in a long-term care facility, recent aminoglycoside use, and older age were all noted to be independent risk factors for FQ resistance among patients with nosocomial E coli and K pneumoniae infections. Efforts should be directed at recognition and modification of these risk factors to curb the rise in FQ resistance and preserve the utility of these agents in the treatment of common nosocomial gram-negative infections.     

Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.     

老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌耐药性分析

目的：监测老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌的耐药性。为临床合理应用抗生素提供依据。方法：对我院下呼吸道感染患者中分离出的肺炎克雷伯菌和大肠埃希菌240株，以Kirby-Bauer(K-B)琼脂扩散法作药敏试验；以美国临床实验室标准委员会（NCCLS）1999年推荐的表型确认试验检测超广谱β－内酰胺酶（ESBLs）。结果：老年组和非老年组肺炎克雷伯菌和大肠埃希菌对14例抗生素的耐药率分别为阿莫西林93．2％和87．3％，哌拉西林57．1％和42．9％、头孢呋新51．4％和33．3％、头孢噻肟40．1％和17．5％、头孢他啶13．6％和3．2％、头孢曲松39．0％和17．5％、头孢哌酮37．3％和15．9％，头孢吡肟10．2％和3．2％、阿米卡星47．5％和34．9％，环丙沙星54．2％和38．1％、亚胺培南15．9％、头孢吡肟10．2％和3．2％、阿米卡星47．5％和34．9％、环丙沙星54．2％和38．1％，亚胺培南0和0、头孢哌酮／舒巴坦0和0、哌拉西林／三唑巴坦1．1％和0、头孢美唑9．6％和4．8％。78株肺炎克雷伯菌和大肠埃希菌被证实为产ESBLs菌，ESBLs检测出率为32．5％（78／240），其中老年组ESBLs检出率为38．4％（68／177），非老年组ESBLs检出率为15．9％（10／63）。亚胺培南，头孢哌酮／舒巴坦，哌拉西林／三唑巴坦和头孢美唑对产ESBLs菌的耐药率最低，分别为0、0、2．6％和12．8％。结论：老年下呼吸道感染患者肺炎克雷伯菌和大肠埃希菌的耐药率和ESBLs检出率均显著高于非老年患者；亚胺培南，头孢哌酮／舒巴坦、哌拉西林／三唑巴坦和头孢美唑是治疗由产ESBLs菌引起感染的有效抗生素。     

老年肝胆疾病患者大肠埃希菌血流感染的临床特点分析

目的：分析老年肝胆疾病患者大肠埃希菌血流感染的临床特点及耐药性,为临床治疗提供依据。方法回顾性分析2009年－2012年于解放军三二医院住院的57例老年肝胆疾病患者血流感染大肠埃希菌的临床特点及药敏试验结果。计量资料组间比较采用 t 检验,计数资料组间比较采用χ2检验。结果57例老年肝胆疾病患者血流感染大肠埃希菌,其中基础疾病以肝硬化为主,感染来源以自发性细菌性腹膜炎为主,超广谱β－内酰胺酶（ESBL）阳性24株,阳性率为42．1％。二者在年龄、性别、基础疾病、原发病灶、体温峰值、白细胞计数及中性粒细胞百分比等方面比较,差异均无统计学意义（P 值均＞0．05）。除亚胺培南／西司他丁、美罗培南、头孢哌酮／舒巴坦、替卡西林／克拉维酸及米诺环素外,ESBL 阳性大肠埃希菌的耐药性均高于 ESBL 阴性大肠埃希菌,差异具有统计学意义（P 值均＜0．05）。发生感染性休克、肝性脑病及急性肾损伤患者的病死率要高于无发生者,差异有统计学意义（χ2值分别为9．541、7．622、9．733,P 值均＜0．05）。结论老年肝胆疾病患者血流感染大肠埃希菌 ESBL 阳性耐药性高,出现严重并发症者预后不良,应尽早联合抗感染治疗及预防,控制严重并发症以降低病死率。     

大肠埃希菌和肺炎克雷伯菌耐药性和耐药质粒谱分析

目的研究大肠埃希菌(Escherichiacoli)和肺炎克雷伯菌(Klebsiella peumoniae)临床分离株耐药性及其质粒谱变化。方法对福建医科大学2所附属医院分离的E.coli和K.peumoniae共53株行药敏试验,检出产超广谱β-内酰胺酶(ESBLs)的菌株用碱变性法提取质粒,采用0.8%琼脂糖凝胶电泳分析质粒谱。结果产ESBLs菌株对多数青霉素和头孢菌素类抗生素耐药,对碳青霉烯类和酶抑制剂敏感(P0.05)。不产ESBLsE.coli菌对喹诺酮类的敏感性高于产酶菌株(P0.01)。受检菌株对丁胺卡那霉素的敏感性较高。产ESBLs菌株60.0%检出质粒,其中50%携带0.9 kb质粒。对环丙沙星耐药的E.coli,50%携带4.2 kb质粒;4株对丁胺卡那霉素耐药的E.coli中,2株携带9.4kb质粒。结论E.coli和K.peumoniae产ESBLs主要由质粒介导。0.9 kb质粒可能与产ESBLs有关;4.2 kb的质粒可能与环丙沙星耐药有关;9.4 kb质粒可能与丁胺卡那霉素耐药有关。     

Perspectives of beta-lactamases inhibitors in therapy of infections caused by Escherichia coli or Klebsiella with plasmidic resistance to third generation cephalosporins

Summary New plasmidic -lactamases inactivating so far stable cephalosporins, aztreonam and cephamycins restrict the use of these antibiotics in therapy of infections, e.g., byEscherichia coli and Klebsiella. Thus, combinations of -lactamase inhibitors and -lactam antibiotics were investigatedin vitro with regard to their therapeutic perspectives. Minimal inhibitory concentrations and the kinetics of killing in a pharmacodynamic model were determined. Extended broad spectrum betalactamases (EBS--lactamases) representative both for the TEM- and SHV-type were included. None of the available fixed combinations of penicillins and -lactamase inhibitors appears useful for therapy of infections caused by producers of EBS--lactamases. In contrast, combinations of piperacillin and tazobactam or sulbactam plus cephalosporins (cefoperazone, cefotaxime, ceftazidime) or aztreonam are highly active (both by their MICs and bactericidal activity) against TEM-type EBS--lactamases, but less promising for the SHV-type EBS--lactamases, and plasmidic cephamycinase. Of the -lactams available, the monobactam carumonam and the carbapenems (imipenem, meropenem) remain safe in infections caused byE. coli and Klebsiella EBSBase producers.

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Therapeutische Perspektiven von -Laktamase-Inhibitoren bei Infektionen durch Escherichia coli oder Klebsiella mit plasmid-determinierter Resistenz gegenüber Drittgenerationscephalosporinen

Zusammenfassung Neue plasmid-kodierte -Laktamasen inaktivieren bisher stabile Cephalosporine, Aztreonam und Cephamycine. Sie schränken damit die therapeutische Sicherheit dieser Antibiotika bei Infektionen zum Beispiel durchEscherichia coli oder Klebsiellaarten ein. Deshalb wurden die therapeutischen Perspektiven von Kombinationen aus -Laktamase-Inhibitoren und -Laktam-Antibiotikain vitro analysiert. Die minimalen Hemmkonzentrationen (MHK) wurden gemessen. Zu einem pharmakokinetischen Modell wurde die Abtötungskinetik bestimmt. Einbezogen wurden Enzyme sowohl aus der TEM- als auch der SHV-Reihe. Keine der beiden zugelassenen festen Kombinationen aus Penicillinen und -Laktamase-Inhibitoren erwies sich als erfolgversprechend für die Therapie von Infektionen durch Stämme, welche -Laktamasen mit erweitertem Spektrum produzieren. Demgegenüber waren Kombinationen aus Piperacillin und Tazobactam oder Sulbactam mit Cephalosporinen (Cefoperazon, Cefotaxim, Ceftazidim) oder Aztreonam sowohl aufgrund ihrer MHK-Werte als auch ihrer bakteriziden Aktivität im pharmakodynamischen Modell hochaktiv gegenüber TEM--Laktamasen mit erweitertem Spektrum, jedoch weniger wirksam bei Stämmen mit neuen Enzymen der SHV-Reihe und plasmid-kodierter Cephamycinasen. Unter den derzeit vorhandenen -Laktam-Antibiotika kommt anhand ihrerIn-vitro-Aktivität dem Monobactam Carumonam sowie den Carbapenemen (Impipenem, Meropenem) auch ohne -Laktamase-Inhibitor die größte therapeutische Sicherheit bei Infektionen durchE. coli und Klebsiella-Stämme mit der Fähigkeit zur Synthese von -Laktamasen mit erweitertem Spektrum zu.

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Symposium 2nd Biennial Conference on Chemotherapy of Infectious Diseases and Malignancies, Montreux, March 5^th–8^th, 1989.

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Supported by Pfizer GmbH, Karlsruhe, FR Germany.     

Escherichia coli and Klebsiella vaccines and immunotherapy

A polyvalent vaccine has been prepared from the capsular polysaccharide of 24 different serotypes of Klebsiella spp. Nearly 200 volunteers have received this vaccine. It is very well tolerated and elicits both binding (ELISA) and functional antibody to 21 of 24 antigens. Antibodies were also detected against 10 serotypes not included in the vaccine. An immunoglobulin for intravenous use (IVIG) was more protective in mouse lethality assays and enhanced opsonophagocytic killing of bacteria more than standard, nonhyperimmune globulin. A monovalent E. coli conjugate vaccine against O18ac antigen was safe and highly immunogenic in humans. A 12-valent conjugate vaccine elicits good levels of antibody in rabbits, and will soon undergo phase I testing in humans. These vaccines might best be used for inducing antibody in donor plasma that could be made into IVIG for passive administration.     

严重肝病伴糖尿病患者大肠埃希菌血流感染临床分析

目的：分析严重肝病伴糖尿病患者大肠埃希菌血流感染的临床特点及耐药性,为临床合理应用抗菌药物提供依据。方法回顾性分析2009年至2012年住院的严重肝病合并糖尿病血流感染大肠埃希菌患者的临床特点及药敏结果。结果严重肝病合并糖尿病血流感染大肠埃希菌患者共47例,基础疾病以肝硬化为主,感染来源以自发性细菌性腹膜炎为主,ESBL阳性22株,阳性率46．81％。ESBL阳性大肠埃希菌耐药性高于 ESBL 阴性大肠埃希菌,但两者在年龄、性别、基础疾病、原发病灶、体温峰值、白细胞计数及中性粒细胞百分比等方面比较均差异无统计学意义,发生感染性休克者的病死率要高于无感染性休克者。结论严重肝病合并糖尿病患者血流感染病情危重,预后不良,应尽早进行正确的综合治疗和抢救以降低病死率。     

Reovirus-like agent and enterotoxigenic Escherichia coli infections in pediatric diarrhea in the Philippines.

Of 82 children hospitalized with diarrhea in the Philippines during January-June 1976, 14 (17%) had infections due to a reovirus-like agent as determined by detection of viral particles in stools by electron microscopy (12 [15%] of 82) and/or by a rise in titer of antibody to the serologically related Nebraska calf diarrhea virus (eight [20%] of 39). Escherichia coli producing heat-labile enterotoxin were found in six (7%) of 82 ill children and two (4%) of 49 healthy control children, while E. coli producing heat-stable enterotoxin were isolated from three children with diarrhea and two without gastroenteritis. Thirty-eight percent of enterotoxigenic E. coli isolated from children with diarrhea, but only 6% of isolates from healthy control, were of serotypes similar to those of enterotoxigenic E. coli isolated in previous studies of these pathogens by other investigators in geographically diverse areas (serotypes O6:H16, O8:H9, and O78:H12) (P less than 0.05). Eight (10%) of the children had infections with multiple enteric pathogens.     

CTX-M-producing Escherichia coli and Klebsiella pneumoniae isolated from community-acquired urinary tract infections in Valledupar,Colombia

ObjectiveDescribe the presence of CTX-M-1 phylogenetic subgroup extended-spectrum β-lactamases (ESBL), associated with TEM and SHV genes, and the gene encoding cephalosporinase, CMY-2 in Escherichia coli and Klebsiella pneumoniae isolates from community-acquired urinary tract infections.Methods102 E. coli and 21 K. pneumoniae were collected from patients with culture-proven urinary tract infection (UTI), during February and March, 2011. Antimicrobial susceptibility test was performed by disk diffusion according to the standards of the Clinical Laboratory Standard Institute. Screening for cephalosporins-resistant E. coli and K. pneumoniae was performed by PCR assay for bla_TEM, bla_SHV, bla_CTX-M-1,_-2,_-8,_-9, bla_PER-2 and bla_CMY-2 genes. Statistical analysis was performed by chi-squared test and multivariate logistic regression analysis.ResultsESBL production was detected in 12 (11.7%) E. coli and four (19%) K. pneumoniae isolates. TEM ESBLs were detected in seven E. coli and three K. pneumoniae isolates. SHV ESBLs were found in four K. pneumoniae isolates. CTX-M-1 phylogenetic subgroup was positive in seven E. coli and three K. pneumoniae isolates. CMY-2 β-lactamase gene was detected in nine E. coli and one K. pneumoniae isolates. A signi?cant association of ESBL expression in E. coli was observed with resistance to tobramycin (p ≤ 0.001), tetracycline (p = 0.043), and ciprofloxacin (p ≤ 0.001). In K. pneumoniae isolates, significant association was found with resistance to tobramycin and ciprofloxacin (p = 0.006), and trimethoprim-sulfamethoxazole (p = 0.043). Multivariate analyses did not show association between ESBL production in E. coli and K. pneumoniae, and resistance to non-β-lactams drugs.ConclusionsCTX-M ESBL in uropathogens isolated from the community is cause for concern due to the enormous potential for multidrug resistance from strains that produce these enzymes, which could lead to failure of empirically-administered therapies and development of complicated UTIs.     

产超广谱β-内酰胺酶大肠埃希菌和肺炎克雷伯菌的分布及耐药性分析

目的了解医院产超广谱β-内酰胺酶（ESBLs）大肠埃希菌和肺炎克雷伯菌的分布及耐药性特点。方法对我院2004年7月～2006年7月间各类临床标本分离出的大肠埃希菌307株和肺炎克雷伯菌202株，用CLSI／NCCLS推荐的表型确证法检测其ESBLs，采用K-B纸片琼脂扩散法进行药敏试验，分析产ESBLs菌株的分布及耐药性。结果大肠埃希菌和肺炎克雷伯菌产ESBLS菌株的检出率分别为38．4％（118／307）和31．7％（64／202），主要分布于尿和痰、咽拭子中，病区主要集中于肺科、神经外科、感染科、泌尿外科、ICU室。产ESBLs菌株对亚胺培南和美罗培南呈高度敏感，对哌托西林／三唑巴坦、头孢哌酮／舒巴坦、头孢西丁耐药率较低，对其他抗菌药物均出现较高耐药。结论产ESBLS的大肠埃希菌和肺炎克雷伯菌分布在不同病区的不同标本中，碳青霉烯类抗生素亚胺培南和美罗培南是治疗产ESBLS菌株感染的较佳药物。     

Conjugal transfer of multiple antibiotic resistance from hospital isolates of Klebsiella to Escherichia coli

Six independent isolates of Klebsiella from hospital environmental sources in Malaysia were found to be resistant to at least ampicillin, carbenicillin, cefoperazone, chloramphenicol, gentamicin and tetracycline. On the basis of their antibiograms, they were divided into four antibiogroups. They transferred all or part of their multiple antibiotic resistance traits to E. coli by conjugation. The results suggest that these Klebsiella strains harbour self-transmissible R plasmids. The significance of these findings are discussed.     

The clinical characteristics analysis of Escherichia coli bloodstream infection

<正>Objective To explore the clinical features of Escherichia coli bloodstream infection.Methods The clinical data of underlying diseases,antimicrobial susceptibility,temperature at blood sampling,results of routine blood tests,venous catheterization,therapy and prognosis of Escherichia coli bloodstream infection in the First Affilia-     

Comparison of Escherichia coli and Klebsiella pneumoniae liver abscesses

BACKGROUND: Escherichia coli and Klebsiella pneumoniae are the most common causative pathogens of pyogenic liver abscesses. The objective of this study was to compare outcome between patients with liver abscesses due to E coli and those with liver abscesses caused by K pneumoniae; we also aimed to identify separately the predictors of mortality in the 2 groups. METHODS: We conducted a retrospective study of 202 patients who presented with pyogenic liver abscesses caused by either E coli or K pneumoniae from July 2000 to June 2005. Outcome of the patients was analyzed by exact logistic regression with adjustment for baseline and clinical covariates. Significant predictors of mortality in the E coli and the K pneumoniae groups were investigated by multivariate analysis of demographic and clinical variables in each group. RESULTS: Of the 202 patients (128 men and 74 women; age range, 19 to 89 years), pyogenic liver abscess was due to E coli infection in 55 patients and K pneumoniae in 147 patients. In contrast to patients with K pneumoniae, patients with E coli liver abscess were more likely to be older and female, have a biliary abnormality or malignancy, pleural effusion, polymicrobial infection with anaerobic or multi-drug-resistant organisms, a higher APACHE II score, and to have been treated initially with ineffective antibiotics; they were also less likely to have diabetes mellitus. The cause of K pneumoniae liver abscess was often cryptogenic. The sensitivity, specificity, positive predictive value, and likelihood ratio of the presence of biliary disorders and coexisting malignancy as a predictive parameter of E coli liver abscess were 25%, 96%, 67%, and 5.45/1, respectively. The sensitivity, specificity, positive predictive value, and likelihood ratio of the presence of diabetes mellitus with an abscess of cryptogenic origin as a predictive parameter of K pneumoniae liver abscess were 39%, 84%, 81%, and 2.36/1, respectively. There was no significant difference in mortality between patients with E coli and those with K pneumoniae infections (26% vs 4%; adjusted OR, 4.2; 95% CI, 0.63 to 27; P = 0.105). However, for patients with liver abscess caused by E coli, the APACHE II score at admission (OR, 1.7; 95% CI, 1.1 to 2.6; P = 0.021), malignancy (OR, 26; 95% CI, 1.8 to 370; P = 0.016), and right-lobe abscess (OR, 0.0029; 95% CI, 0.00010 to 0.15; P = 0.004) were significant predictors of death, whereas uremia (OR, 52; 95% CI, 3.5 to 750; P = 0.004) and multi-drug-resistant isolates (OR, 26; 95% CI, 2.3 to 290; P = 0.009) were significant predictors of death in the K pneumoniae group. CONCLUSIONS: A higher APACHE II score at admission and a higher frequency of coexisting malignancy may have contributed to the higher, although not significant, mortality rate in patients with liver abscess caused by E coli infection. Clinicians should begin with broad antibiotic coverage such as a second-generation cephalosporin and an aminoglycoside with metronidazole when treating liver abscesses with E coli as the likely pathogen due to the high frequency of multi-drug-resistant isolates among E coli isolates.     

Outbreak of catheter-associated Klebsiella oxytoca and Enterobacter cloacae bloodstream infections in an oncology chemotherapy center

BACKGROUND: In March 2004, the Chicago Department of Public Health was notified of a cluster of bloodstream infections with Klebsiella oxytoca and Enterobacter cloacae at a chemotherapy center. Our purpose was to identify the source of the outbreak and prevent further cases. METHODS: The investigation included 103 oncology patients seen at an outpatient oncology chemotherapy center in Chicago during the 16 days before its closure. The outbreak investigation included case identification, retrospective cohort study, review of medical records, microbiologic testing of blood specimens, environmental cultures, and pulsed-field gel electrophoresis. The main outcome measure was infection with K oxytoca, E cloacae, or both, and the Mantel-Haenszel chi(2) test was used to assess risk of infection in relation to presence of central venous catheter. RESULTS: Among the 103 patients, risk of infection was associated with the presence of central venous catheter (relative risk undefined, P<.001). Twenty-seven patients had blood cultures that grew K oxytoca, E cloacae, or both, and all had central venous catheters that were flushed with isotonic sodium chloride solution at the clinic from February 17 through March 3, 2004. Isolates of K oxytoca and E cloacae were matched by pulsed-field gel electrophoresis to K oxytoca and E cloacae isolates obtained from multiple predrawn syringes and from the intravenous fluid and administration set in use in the clinic at the time of its closing. CONCLUSIONS: The injection of contaminated isotonic sodium chloride solution through the venous catheters of attendees at the clinic likely provided the opportunity for bloodstream infections in these 27 case patients. This outbreak highlights the need for continued emphasis on safe injection practices and suggests the need for guidelines and recommendations tailored to outpatient settings.     

产超广谱β内酰胺酶菌株中质粒头孢菌素酶的研究

目的 调查产超广谱β内酰胺酶(ESBLs)的大肠埃希菌和肺炎克雷伯菌中质粒头孢菌素酶(AmpC酶)的发生率及其基因型。方法 收集北京朝阳医院2001年1～12月头孢西丁耐药的产ESBLs的24株大肠埃希菌、8株肺炎克雷伯菌,采用等电聚焦电泳测定β内酰胺酶的等电点;接合试验证实酶基因有无可转移性;脉冲场凝胶电泳(PFGE)确定耐药株的亲缘关系;对AmpC酶基因进行多重PCR及序列分析确定其基因型。结果 2001年北京朝阳医院ESBLs的发生率,大肠埃希菌为16.8％(49／292),肺炎克雷伯菌为160.5％(35／212);ESBLs株中质粒AmpC酶的发生率,大肠埃希菌为2．0％(1／49),肺炎克雷伯菌为17．1％(6／35)。这7株菌均产生DHA-1型AmpC酶;1株肺炎克雷伯菌可将头孢西丁耐药性传给受菌体。该7株菌都产TEM-1酶、5株产CTX-M-3型ESBL、2株产SHV-12型ESBL;该7株菌携带质粒2～5个,且都有约33～36kb的大质粒。PFGE发现这7株菌来自多个不同的克隆株。结论 北京朝阳医院ESBL阳性的大肠埃希菌和肺炎克雷伯菌中,有7株既产DHA-1型质粒AmpC酶,又产CTX-M-3或SHV-12 ESBL。这7株菌来自多个不同的克隆株。