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1.400038 重庆,陆军军医大学(第三军医大学)第一附属医院:预防保健科
2.400038 重庆,陆军军医大学(第三军医大学)第一附属医院:老年病科
3.400038 重庆,陆军军医大学(第三军医大学)第一附属医院:药剂科
[熊玮,E-mail: xiongwei64@126.com XIONG Wei, E-mail: xiongwei64@126.com
收稿:2020-05-19,
修回:2020-07-01,
纸质出版:2020-10-30
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宋洁, 陈先华, 朱科, 等. 头孢他啶/阿维巴坦与氨曲南联合对临床分离碳青霉烯耐药肺炎克雷伯菌的协同作用[J]. 第三军医大学学报, 2020,42(20):2026-2030.
Jie SONG, Xianhua CHEN, Ke ZHU, et al. Synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant
宋洁, 陈先华, 朱科, 等. 头孢他啶/阿维巴坦与氨曲南联合对临床分离碳青霉烯耐药肺炎克雷伯菌的协同作用[J]. 第三军医大学学报, 2020,42(20):2026-2030. DOI: 10.16016/j.1000-5404.202005151.
Jie SONG, Xianhua CHEN, Ke ZHU, et al. Synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant
目的
2
探讨头孢他啶/阿维巴坦与氨曲南联合对碳青霉烯耐药肺炎克雷伯菌的协同作用。
方法
2
采用琼脂平板倍比稀释法测定细菌的最低抑菌浓度,PCR扩增碳青霉烯酶基因和超广谱β-内酰胺酶基因,RT-PCR检测碳青霉烯酶基因的表达量,多位点序列分型分析菌株的基因型,棋盘法测定头孢他啶/阿维巴坦与氨曲南的协同作用。
结果
2
10株碳青霉烯高耐药菌株除对替加环素敏感性较高外,对其他实验药物均具有较高的耐药性。β-内酰胺酶基因NDM、CTX-M和SHV在菌株中分布广泛,且对碳青霉烯耐药高的菌株其碳青霉烯酶基因表达也较高(
r
=0.805,
P
=0.029)。菌株共有4个ST型,ST11是最流行的基因型,NDM基因存在于3种不同的基因型菌株中。头孢他啶/阿维巴坦与氨曲南联合对7株碳青霉烯耐药肺炎克雷伯菌具有协同作用,3株为无关作用。
结论
2
碳青霉烯耐药肺炎克雷伯菌的高耐药与其携带的耐药基因相关,头孢他啶/阿维巴坦与氨曲南有较高的协同作用。
Objective
2
To explore the synergistic effect of ceftazidime/avicarbam combined with aztreonam against carbapenem-resistant isolates of
Klebsiella pneumoniae
(CRKP).
Methods
2
We collected 10 clinical isolates of CRKP from our hospital and determined the minimal inhibitory concentrations of the commonly used antibiotics in these isolates using agar plate double-dilution method. The carbapenemase genes and extended-spectrum β-lactamase genes of the bacteria were amplified by PCR
and the expression of carbapenemase genes was detected by RT-PCR. The bacterial genotypes were analyzed with multilocus sequence typing. The synergistic effect of ceftazidime/avicarbam combined with aztreonam against these CRKP isolates was determined using the checkerboard method.
Results
2
The 10 CRKP isolates were all sensitive to tigecycline but highly resistant to all the other antibiotics tested. The β-lactamase genes (NDM
CTX-M and SHV) were widely distributed in these isolates
and the strains with a high resistance to carbapenem also had high expression levels of carbapenemase genes (r=0.805
P
=0.029). Four distinct ST genotypes were identified among the CRKP strains
and the genotype ST11 had the highest epidemic potential; NDM gene was present in the strains of 3 different ST genotypes. Cefta
zidime/avicarbam combined with aztreonam showed a synergistic inhibitory effect in 7 CRKP strains and produced irrelevant effects in the other 3 strains.
Conclusion
2
The high resistance of CRKP strains can be attributed to the resistance genes they carry
and the combination of ceftazidime/avicarbam and aztreonam can produce a strong synergistic inhibitory effect in these strains.
HU F P, GUO Y, YANG Y, et al . Resistance reported from China antimicrobial surveillance network (CHINET) in 2018[J ] . Eur J Clin Microbiol Infect Dis, 2019, 38(12): 2275-2281 . DOI: 10.1007/s10096-019-03673-1.
LAGACÉ-WIENS P, WALKTY A, KARLOWSKY J A. Ceftazidime-avibactam : an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections[J ] . Core Evid, 2014, 9: 13-25. DOI: 10.2147/CE.S40698.
FRITZENWANKER M, IMIRZALIOGLU C, HEROLD S, et al . Treatment options for Carbapenem-resistant gram-Negative infections [J ] . Dtsch Arztebl Int, 2018, 115(20/21): 345-352. DOI: 10.3238/arztebl.2018.0345.
CHEN Z H, LI H X, FENG J, et al . NDM-1 encoded by a pNDM-BJ01-like plasmid p3SP-NDM in clinical Enterobacter aerogenes[J ] . Front Microbiol, 2015, 6: 294. DOI: 10.3389/fmicb.2015.00294..
XIE S J, FU S M, LI M W, et al . Microbiological characteristics of carbapenem-resistant Enterobacteriaceae clinical isolates collected from county hospitals[J ] . Infect Drug Resist, 2020, 13: 1163-1169. DOI: 10.2147/IDR.S248147..
BONAPACE C R, BOSSO J A, FRIEDRICH L V, et al . Comparison of methods of interpretation of checkerboard synergy testing[J ] . Diagn Microbiol I nfect Dis, 2002, 44(4): 363-366. DOI: 10.1016/s0732-8893(02)00473-x.
ODDS F C. Synergy, antagonism, and what the chequerboard puts between them[J]. J Antimicrob Chemother, 2003, 52(1): 1. DOI: 10.1093/jac/dkg301.
WANG Q, WANG X J, WANG J, et al . Phenotypic and genotypic characterization of carbapenem-resistant Enterobacteriaceae: data from a longitudinal large-scale CRE study in China (2012-2016)[J ] . Clin Infect Dis, 2018, 67(suppl_2): S196-S205. DOI: 10.1093/cid/ciy660.
TIAN D, PAN F, WANG C, et al . Resistance phenotype and clinical molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae among pediatric patients in Shanghai [J ] . Infect Drug Resist, 2018, 11: 1935-1943. DOI: 10.2147/IDR.S175584.
YONG D, TOLEMAN M A, GISKE C G, et al . Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India[J ] . Antimicrob Agents Chemother, 2009, 53(12): 5046-5054. DOI: 10.1128/AAC.00774-09..
ZHOU H, ZHANG K, CHEN W, et al . Epidemiological characteristics of carbapenem-resistant Enterobacteriaceae collected from 17 hospitals in Nanjing district of China[J ] . Antimicrob Resist Infect Control, 2020, 9: 15. DOI: 10.1186/s13756-019-0674-4..
CHEN Y, LIAO K, HUANG Y, et al . Determining the susceptibility of carbapenem resistant Klebsiella pneumoniae and Escherichia coli strains against common disinfectants at a tertiary hospital in China [J ] . BMC Infect Dis, 2020, 20(1): 88. DOI: 10.1186/s12879-020-4813-6..
ALATOOM A, ELSAYED H, LAWLOR K, et al . Comparison of antimicrobial activity between ceftolozane-tazobactam and ceftazidime-avibactam against multidrug-resistant isolates of Escherichia coli , Klebsiella pneumoniae, and Pseudomonas aeruginosa[J ] . Int J Infect Dis, 2017, 62: 39-43. DOI: 10.1016/j.ijid.2017.06.007..
HOBSON C A, BONACORSI S, FAHD M, et al . Successful treatment of Bacteremia due to NDM-1-producing Morganella morganii with aztreonam and ceftazidime-avibactam combination in a pediatric patient with Hematologic Malignancy [J ] . Antimicrob Agents Chemother, 2019, 63(2): e02463-18. DOI: 10.1128/AAC.02463-18.
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