非小细胞肺癌患者化疗期间肺部感染分离的产超广谱β-内酰胺酶病原菌耐药基因检测
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摘要
目的分析非小细胞肺癌(NSCLC)患者化疗期间肺部感染分离的产超广谱β-内酰胺酶(ESBLs)病原菌耐药性及基因表型,以指导临床治疗。方法统计2016年6月-2017年10月收治的420例NSCLC患者在化疗期间肺部感染发生情况,采集感染患者临床标本进行细菌培养及药敏试验,采用PCR技术检测产ESBLs病原菌的耐药基因。结果 420例NSCLC患者在化疗期间,97例患者发生肺部感染,感染率为23.10%;共检出革兰阴性菌87株,产ESBLs细菌35株,占40.23%,其中肺炎克雷伯菌占37.14%、大肠埃希菌和铜绿假单胞菌各占28.57%;35株产ESBLs细菌对青霉素及头孢菌素高度耐药,其中对氨苄西林/克拉维酸、氨苄西林、头孢唑林、头孢曲松的耐药率达100.00%,对β-内酰胺类抗菌药物/酶抑制剂复合物部分耐药,耐药率为14.29%～20.00%,对碳青霉烯类抗菌药物保持良好敏感性;TEM型菌株检出率最高,占31.43%,其次为CTX-M-9型菌株,占25.71%,同时携带两种或两种以上基因型的菌株5株,占14.29%。结论 NSCLC化疗患者肺部感染产ESBLs细菌具有多药耐药的基因表型特征,临床应加强对肺部感染产ESBLs细菌的监测,并根据药敏结果指导用药。
OBJECTIVE To analyze the drug resistance of extended spectrumβ-lactamases(ESBLs)-producing pathogens isolated from non-small cell lung cancer(NSCLC)patients with pulmonary infection during chemotherapy and observe the genotypes so as to provide guidance for clinical treatment.METHODS The incidence of pulmonary infection in 420 NSCLC patients who received chemotherapy from Jun 2016 to Oct 2017 was statistically analyzed,the bacterial culture and drug susceptibility testing were performed,and the drug resistance genes in the ESBLs-producing pathogens were detected by using PCR.RESULTS Of the 420 NSCLC patients who received the chemotherapy,97 had pulmonary infection,with the infection rate 23.10%.A total of 87 strains of gram-negative bacteria were isolated,35(40.23%)of which were ESBLs-producing bacteria,and Klebsiella pneumoniae accounted for 37.14%,and Escherichia coli and Pseudomonas aeruginosa accounted for 28.57% and 28.57%,respectively.The 35 strains of ESBLs-producing bacteria were highly resistant to penicillin and cephalosporins,and the drug resistance rates to ampicillin-clavulanic acid,ampicillin,cefazolin and ceftriaxone were as high as100.00%,the drug resistance rates toβ-lactams antibiotics and enzyme inhibitor compounds varied from 14.29%to 20.00%,and the strains maintained high susceptibility to carbapenems antibiotics.The strains carrying with the TEM genotype were dominant,accounting for 31.43%,followed by the strains carrying with the CTX-M-9 genotype(25.71%),and 5 strains carried with two or more than two genotypes,accounting for 14.29%.CONCLUSION The ESBLs-producing bacteria that are isolated from the NSCLC patients with pulmonary infection show multidrug-resistant genetic phenotypes.It is necessary for the hospital to strengthen the surveillance of the ESBLs-producing bacteria causing the pulmonary infection and use antibiotics based on the result of drug susceptibility testing.
OBJECTIVE To analyze the drug resistance of extended spectrumβ-lactamases(ESBLs)-producing pathogens isolated from non-small cell lung cancer(NSCLC)patients with pulmonary infection during chemotherapy and observe the genotypes so as to provide guidance for clinical treatment.METHODS The incidence of pulmonary infection in 420 NSCLC patients who received chemotherapy from Jun 2016 to Oct 2017 was statistically analyzed,the bacterial culture and drug susceptibility testing were performed,and the drug resistance genes in the ESBLs-producing pathogens were detected by using PCR.RESULTS Of the 420 NSCLC patients who received the chemotherapy,97 had pulmonary infection,with the infection rate 23.10%.A total of 87 strains of gram-negative bacteria were isolated,35(40.23%)of which were ESBLs-producing bacteria,and Klebsiella pneumoniae accounted for 37.14%,and Escherichia coli and Pseudomonas aeruginosa accounted for 28.57% and 28.57%,respectively.The 35 strains of ESBLs-producing bacteria were highly resistant to penicillin and cephalosporins,and the drug resistance rates to ampicillin-clavulanic acid,ampicillin,cefazolin and ceftriaxone were as high as100.00%,the drug resistance rates toβ-lactams antibiotics and enzyme inhibitor compounds varied from 14.29%to 20.00%,and the strains maintained high susceptibility to carbapenems antibiotics.The strains carrying with the TEM genotype were dominant,accounting for 31.43%,followed by the strains carrying with the CTX-M-9 genotype(25.71%),and 5 strains carried with two or more than two genotypes,accounting for 14.29%.CONCLUSION The ESBLs-producing bacteria that are isolated from the NSCLC patients with pulmonary infection show multidrug-resistant genetic phenotypes.It is necessary for the hospital to strengthen the surveillance of the ESBLs-producing bacteria causing the pulmonary infection and use antibiotics based on the result of drug susceptibility testing.
引文
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[11]Al-Mayahie S,Al Kuriashy JJ.Distribution of ESBLs among Escherichia coli isolates from outpatients with recurrent UTIs and their antimicrobial resistance[J].J Infect Dev Ctries,2016,10(6):575-583.
[12]徐春泉,吴庆,张雪青,等.大肠埃希菌产超广谱β-内酰胺酶基因型及毒力因子相关性研究[J].疾病监测,2014,29(4):316-320.
[13]El Moujaber G,Osman M,Rafei R,et al.Molecular mechanisms and epidemiology of resistance in Streptococcus pneumoniae in the Middle East region[J].J Med Microbiol,2017,66(7):847-858.
[14]Karlowsky JA,Biedenbach DJ,Kazmierczak KM,et al.Activity of ceftazidime-avibactam against extended-spectrumand ampCβ-lactamase-producing Enterobacteriaceae collected in the INFORM Global Surveillance Study from 2012to 2014[J].Antimicrob Agents Chemother,2016,60(5):2849-2857.
[15]Woerther PL,Burdet C,Chachaty E,et al.Trends in human fecal carriage of extended-spectrumβ-lactamases in the community:toward the globalization of CTX-M[J].Clin Microbiol Rev,2013,26(4):744-758.
[16]张晶晶,谢永富,黄印启,等.超广谱β-内酰胺酶肺炎克雷伯菌底物筛选与耐药性及耐药基因分型研究[J].中国病原生物学杂志,2016,11(7):661-664.
[2]Clinical and Laboratory Standards Institute.Performance standards for antimicrobial susceptibility testing:twenty-second informational supplement[S].2014,M100-S24.
[3]张淼,刘文静,郝璐,等.晚期肺癌合并慢阻肺化疗后肺部感染的病原谱及耐药性分析[J].临床肺科杂志,2015,20(9):1611-1614.
[4]诸君,赵丹妹,陈建国,等.肺癌患者化疗后肺部感染病原菌分布与耐药性分析[J].检验医学与临床,2017,14(21):3170-3172.
[5]Tomono T,Kajita M,Yano K,et al.Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multidrug resistance mediated by P-glycoprotein[J].Biochem Biophys Res Commun,2016,76(4):183-187.
[6]Tabchi S,Weng X,Blais N.Severe agranulocytosis in a patient with metastatic non-small-cell lung cancer treated with nivolumab[J].Lung Cancer,2016,39(9):123-126.
[7]沈旸,涂厉标,李旭梅.产超广谱β-内酰胺酶肺炎克雷伯菌与大肠埃希菌耐药性分析[J].中国现代应用药学,2013,30(4):429-433.
[8]Chandrasekhar D,Chalilparambil J,Kallungal SM,et al.Prevalence,risk factors and antimicrobial susceptibility pattern of extended spectrumβ-lactamase-producing bacteria in a tertiary care hospital[J].J Basic Clin Physiol Pharmacol,2016,27(2):155-162.
[9]Saravanan M,Ramachandran B,Barabadi H.The prevalence and drug resistance pattern of extended spectrumβ-lactamases(ESBLs)-producing Enterobacteriaceae in Africa[J].Microb Pathog,2017,28(12):180-192.
[10]王元元,张昭勇,吕军.下呼吸道感染肺炎克雷伯菌耐药性及产ESBLs株危险因素分析[J].湖北医药学院学报,2014,33(3):248-252.
[11]Al-Mayahie S,Al Kuriashy JJ.Distribution of ESBLs among Escherichia coli isolates from outpatients with recurrent UTIs and their antimicrobial resistance[J].J Infect Dev Ctries,2016,10(6):575-583.
[12]徐春泉,吴庆,张雪青,等.大肠埃希菌产超广谱β-内酰胺酶基因型及毒力因子相关性研究[J].疾病监测,2014,29(4):316-320.
[13]El Moujaber G,Osman M,Rafei R,et al.Molecular mechanisms and epidemiology of resistance in Streptococcus pneumoniae in the Middle East region[J].J Med Microbiol,2017,66(7):847-858.
[14]Karlowsky JA,Biedenbach DJ,Kazmierczak KM,et al.Activity of ceftazidime-avibactam against extended-spectrumand ampCβ-lactamase-producing Enterobacteriaceae collected in the INFORM Global Surveillance Study from 2012to 2014[J].Antimicrob Agents Chemother,2016,60(5):2849-2857.
[15]Woerther PL,Burdet C,Chachaty E,et al.Trends in human fecal carriage of extended-spectrumβ-lactamases in the community:toward the globalization of CTX-M[J].Clin Microbiol Rev,2013,26(4):744-758.
[16]张晶晶,谢永富,黄印启,等.超广谱β-内酰胺酶肺炎克雷伯菌底物筛选与耐药性及耐药基因分型研究[J].中国病原生物学杂志,2016,11(7):661-664.