窄谱β-内酰胺酶和Omp突变导致肠杆菌科细菌对头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的敏感性降低

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2022-06-19 DOI:10.33073/pjm-2022-023

Fengzhen Yang, Qi Zhao, Lipeng Wang, Jinying Wu, Lihua Jiang, Li Sheng, Leyan Zhang, Zhaoping Xue, Maoli Yi

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Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla SHV-1 only, and four harbored bla SHV-1 and bla TEM-1B. Two Escherichia coli strains carried bla TEM-1B only, while two Klebsiella oxytoca isolates harbored bla OXY-1-3 and bla OXY-1-1, respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae. Antibiotic susceptibility tests Antibiotics Breakpoint, (μg/ml) Klebsiella pneumoniae Escherichia cou Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO ≤1≥4 ≤0.5 ≤0.5 ≤0.5 ≤0.5 1 ≤0.5 1 ≤0.5 ≤0.5 1 1 CAZ 4 ≥16 1 2 1 4 4 4 4 2 4 1 1 FEP ≤2 216 1 1 0.25 1 2 2 2 0.5 2 1 1 AMC ≤8 ≥32 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 CSL ≤16 ≥64 64 64 64 64 ≥128 128 ≥128 64 128 128 ≥128 TZP ≤16 ≥128 ≥256 ≥256 ≥256 ≥256 2256 2256 ≥256 ≥256 ≥256 ≥256 ≥256 FPT ≤2 ≥16 1 0.5 0.06 0.125 2 1 2 0.25 1 0.125 0.25 FPZ ≤2 216 0.25 0.25 0.06 0.125 0.25 0.25 1 0.125 0.25 0.125 0.125 CZA ≤8 216 1 0.5 0.25 0.25 1 0.25 1 0.5 0.5 0.5 0.25 CZT ≤2 28 2 1 0.5 1 2 2 2 1 1 2 2 CROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results Number Strain ST p-Lactamase gene Promoter sequence mutation Omp mutation El Kpn 45 blaSHV-1, blaTEM-lB none OmpK36, OmpK3 7 E3 Kpn 45 blaSHV-1, blaTEM-lB none OmpK36. OmpK3 7 E4 Kpn 2854 blaSHV-1 none OmpK36, OmpK3 7 E7 Kpn 2358 blaSHV-1 - blaTEM-lB none OmpK36, OmpK3 7 E9 Kpn 2358 blaSHV-1. blaTEM-lB none OmpK36. OmpK3 7 E10 Kpn 18 9 blaSHV-1 none OmpK36. OmpK3 7 Ell Kpn 45 blaSHV-1 none OmpK36, OmpK3 7 E6 Eco 88 blaTEM-lB none none ES Eco 409 blaTEM-1B none none E2 Kox 194 blaOXY-1-3 none OmpK36 mutations. OmpK35 and OmpK 37 deficiency E5 Kox 11 blaOXY-1-1 none no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found.","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"251-256"},"PeriodicalIF":4.6000,"publicationDate":"2022-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/42/pjm-71-251.PMC9252146.pdf","citationCount":"0","resultStr":"{\"title\":\"Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation.\",\"authors\":\"Fengzhen Yang, Qi Zhao, Lipeng Wang, Jinying Wu, Lihua Jiang, Li Sheng, Leyan Zhang, Zhaoping Xue, Maoli Yi\",\"doi\":\"10.33073/pjm-2022-023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. 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OmpK3 7 E4 Kpn 2854 blaSHV-1 none OmpK36, OmpK3 7 E7 Kpn 2358 blaSHV-1 - blaTEM-lB none OmpK36, OmpK3 7 E9 Kpn 2358 blaSHV-1. blaTEM-lB none OmpK36. OmpK3 7 E10 Kpn 18 9 blaSHV-1 none OmpK36. OmpK3 7 Ell Kpn 45 blaSHV-1 none OmpK36, OmpK3 7 E6 Eco 88 blaTEM-lB none none ES Eco 409 blaTEM-1B none none E2 Kox 194 blaOXY-1-3 none OmpK36 mutations. 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引用次数: 0

摘要

头孢哌酮/舒巴坦(CSL)和哌拉西林/他唑巴坦(TZP)因其良好的抗菌活性在中国临床中被广泛使用。CSL和tzp非敏感肠杆菌科通常对头孢曲松(CRO)等广谱头孢菌素耐药。2020年1 - 12月共收集到11株对CSL和TZP耐药但对CRO敏感的非重复肠杆菌科菌株。进行了抗生素敏感性试验和全基因组测序来阐明这种罕见表型的机制。药敏试验结果显示，所有分离株均对头孢他啶、头孢吡肟、头孢吡肟/他唑巴坦、头孢吡肟/齐德巴坦、头孢他啶/阿维巴坦、头孢甲苯/他唑巴坦耐阿莫西林/克拉维酸，敏感。全基因组测序结果显示，7株肺炎克雷伯菌中3株仅携带bla SHV-1, 4株同时携带bla SHV-1和bla TEM-1B。2株大肠埃希菌仅携带bla TEM-1B, 2株产氧克雷伯菌分别携带bla OXY-1-3和bla OXY-1-1。β-内酰胺酶基因及启动子序列未见突变。外膜蛋白(Omp)基因检测结果显示，所有肺炎凯布菌均存在大量的OmpK36和OmpK37错义突变。结果表明，在一株菌株中发现了大量的OmpK36、OmpK35错义突变和OmpK37缺失，而在另一株菌株中未发现OmpK基因。大肠杆菌分离株中未发现Omp突变。这些结果表明，窄谱β-内酰胺酶、TEM-1、SHV-1和OXY-1单独或联合Omp突变参与了cro敏感肠杆菌科细菌对CSL和TZP的抗性。抗生素敏感性试验(μg / ml)肺炎克雷伯菌大肠再Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO≤1≥4≤0.5≤0.5≤0.5≤0.5 - 1≤0.5 1≤0.5≤0.5 CAZ 4≥16 1 1 1 2 1 4 4 4 4 2 4 1 1聚全氟乙丙烯≤2 216年1 1 0.5 0.25 1 2 2 2 2 1 1 8 AMC≤≥32≥128≥128≥128≥128≥128≥128≥128≥128≥128≥128≥128 CSL≤16≥≥64 64 64 64 64 128 128≥128 64 128 128≥128 TZP≤16≥128≥256≥256≥256≥256 256 2256 2256 256≥≥≥256≥256≥256把≤2≥16 1 0.25 0.5 0.06 0.125 - 2 1 2 1 0.125 - 0.25 FPZ≤216 0.25 0.25 0.06 0.125 0.250.25 - 1 0.125 0.25 0.125 0.125 CZA≤8 216 1 0.5 0.25 0.25 0.25 0.5 0.5 0.5 0.25 CZT≤2 28 2 1 0.5 - 1 2 2 2 1 1 2 2 CROceftriaxone CAZceftazidime, FEPcefepime, AMC:阿莫西林clavulanic-acid, CSLcefoperazone / sulbactam TZP: piperadllin / tazobactam,把需要:头孢吡肟tazobactam, FPZ:头孢吡肟/ zidebactam CZA:头孢他啶/ avibactam CZTceftolozane / tazobactam基因测序结果数株圣p-Lactamase基因启动子序列突变Omp突变El Kpn 45 blaSHV-1 blaTEM-lB OmpK36,OmpK3 7 E3 Kpn 45 blaSHV-1、blaTEM-lB无OmpK36。ompk37 E4 Kpn 2854 blaSHV-1无OmpK36, ompk37 E7 Kpn 2358 blaSHV-1 - blaTEM-lB无OmpK36, ompk37 E9 Kpn 2358 blaSHV-1。blem - lb none OmpK36。OmpK3 7 E10 Kpn 18 9 blaSHV-1无。ompk37 7 Ell Kpn 45 blaSHV-1无OmpK36、ompk37 7 E6 Eco 88 blaTEM-lB无无ES Eco 409 blaTEM-1B无无E2 cox 194 blaOXY-1-3无OmpK36突变。OmpK35和OmpK37缺乏症E5 Kox 11 blaOXY-1-1无发现OmpK (OmpK35、OmpK36和OmpK37)基因。

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Diminished Susceptibility to Cefoperazone/Sulbactam and Piperacillin/Tazobactam in Enterobacteriaceae Due to Narrow-Spectrum β-Lactamases as Well as Omp Mutation.

Cefoperazone/sulbactam (CSL) and piperacillin/tazobactam (TZP) are commonly used in clinical practice in China because of their excellent antimicrobial activity. CSL and TZP-nonsusceptible Enterobacteriaceae are typically resistant to extended-spectrum cephalosporins such as ceftriaxone (CRO). However, 11 nonrepetitive Enterobacteriaceae strains, which were resistant to CSL and TZP yet susceptible to CRO, were collected from January to December 2020. Antibiotic susceptibility tests and whole-genome sequencing were conducted to elucidate the mechanism for this rare phenotype. Antibiotic susceptibility tests showed that all isolates were amoxicillin/clavulanic-acid resistant and sensitive to ceftazidime, cefepime, cefepime/tazobactam, cefepime/zidebactam, ceftazidime/avibactam, and ceftolozane/tazobactam. Whole-genome sequencing revealed three of seven Klebsiella pneumoniae strains harbored bla _SHV-1 only, and four harbored bla _SHV-1 and bla _TEM-1B. Two Escherichia coli strains carried bla _TEM-1B only, while two Klebsiella oxytoca isolates harbored bla _OXY-1-3 and bla _OXY-1-1, respectively. No mutation in the β-lactamase gene and promoter sequence was found. Outer membrane protein (Omp) gene detection revealed that numerous missense mutations of OmpK36 and OmpK37 were found in all strains of K. pneumoniae. Numerous missense mutations of OmpK36 and OmpK35 and OmpK37 deficiency were found in one K. oxytoca strain, and no OmpK gene was found in the other. No Omp mutations were found in E. coli isolates. These results indicated that narrow spectrum β-lactamases, TEM-1, SHV-1, and OXY-1, alone or in combination with Omp mutation, contributed to the resistance to CSL and TZP in CRO-susceptible Enterobacteriaceae. Antibiotic susceptibility tests Antibiotics Breakpoint, (μg/ml) Klebsiella pneumoniae Escherichia cou Klebriehd axyoca E1 E3 E4 E7 E9 E10 E11 E6 E8 E2 E5 CRO ≤1≥4 ≤0.5 ≤0.5 ≤0.5 ≤0.5 1 ≤0.5 1 ≤0.5 ≤0.5 1 1 CAZ 4 ≥16 1 2 1 4 4 4 4 2 4 1 1 FEP ≤2 216 1 1 0.25 1 2 2 2 0.5 2 1 1 AMC ≤8 ≥32 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 ≥128 CSL ≤16 ≥64 64 64 64 64 ≥128 128 ≥128 64 128 128 ≥128 TZP ≤16 ≥128 ≥256 ≥256 ≥256 ≥256 2256 2256 ≥256 ≥256 ≥256 ≥256 ≥256 FPT ≤2 ≥16 1 0.5 0.06 0.125 2 1 2 0.25 1 0.125 0.25 FPZ ≤2 216 0.25 0.25 0.06 0.125 0.25 0.25 1 0.125 0.25 0.125 0.125 CZA ≤8 216 1 0.5 0.25 0.25 1 0.25 1 0.5 0.5 0.5 0.25 CZT ≤2 28 2 1 0.5 1 2 2 2 1 1 2 2 CROceftriaxone, CAZceftazidime, FEPcefepime, AMC:amoxicillin clavulanic-acid, CSLcefoperazone/sulbactam, TZP:piperadllin/tazobactam, FPT:cefepime tazobactam, FPZ:cefepime/zidebactam, CZA:ceftazidime/avibactam, CZTceftolozane/tazobactam Gene sequencing results Number Strain ST p-Lactamase gene Promoter sequence mutation Omp mutation El Kpn 45 blaSHV-1, blaTEM-lB none OmpK36, OmpK3 7 E3 Kpn 45 blaSHV-1, blaTEM-lB none OmpK36. OmpK3 7 E4 Kpn 2854 blaSHV-1 none OmpK36, OmpK3 7 E7 Kpn 2358 blaSHV-1 - blaTEM-lB none OmpK36, OmpK3 7 E9 Kpn 2358 blaSHV-1. blaTEM-lB none OmpK36. OmpK3 7 E10 Kpn 18 9 blaSHV-1 none OmpK36. OmpK3 7 Ell Kpn 45 blaSHV-1 none OmpK36, OmpK3 7 E6 Eco 88 blaTEM-lB none none ES Eco 409 blaTEM-1B none none E2 Kox 194 blaOXY-1-3 none OmpK36 mutations. OmpK35 and OmpK 37 deficiency E5 Kox 11 blaOXY-1-1 none no OmpK (OmpK3 5, OmpK36 and OmpK37) gene found.

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.