Li Debao, Li Keyang, Dong Hongliang, Ren Dongmei, Gong Dandan, Jiang Fuguo, Shi Chunhua, Li Junmin, Zhang Qi, Yan Wenjuan, Li Yi
Department of Clinical Laboratory, Jiaozuo People's Hospital, Jiaozuo, Henan, People's Republic of China.
Department of Clinical Pharmacy, Jiaozuo People's Hospital, Jiaozuo, Henan, People's Republic of China.
Infect Drug Resist. 2021 May 10;14:1725-1731. doi: 10.2147/IDR.S306095. eCollection 2021.
Carbapenem-resistant (CRKP) represents a serious problem worldwide. Herein, we describe the evolution of ceftazidime-avibactam (CZA) resistance by sequencing clinical isolates from a patient with CRKP infection undergoing CZA treatment.
In this study, six CRKP strains were isolated from sputum and blood samples of a patient with CRKP infection after intracerebral hemorrhage. Two strains were selected for whole-genome analysis.
Drug susceptibility testing showed that the MIC of CZA for CRKP strains isolated after 6 days of CZA treatment was 64-fold higher than that for three CRKP strains isolated before CZA treatment (4 vs >256 μg/mL), whereas the MIC of imipenem and meropenem was 128-fold (>32 vs 0.25 μg/mL) and 16-fold (> 32 vs 2 μg/mL) lower relatively, respectively. Multilocus sequence typing showed that all six CRKP strains isolated from the patient were ST11 and pulsed-field gel electrophoresis confirmed that they were of the same clone. Two strains were selected for whole-genome analysis. The aspartic acid residue at position 179 in the Ω loop was replaced by a tyrosine residue in the resistant strain, and the plasmid carried a to mutation. The results of the modified carbapenem inactivation method and the carbapenemase inhibitor enhancement and colloidal gold enzyme immunochromatographic assays for were negative.
This is the first report from Henan to show that treatment with CZA for 6 days can cause mutations and change the phenotype from CZA sensitive to resistant. Therefore, routine testing for drug susceptibility and carbapenemase phenotypes should be conducted during treatment with CZA, and genotype determination is essential.
耐碳青霉烯类肺炎克雷伯菌（CRKP）在全球范围内都是一个严重问题。在此，我们通过对一名接受头孢他啶-阿维巴坦（CZA）治疗的CRKP感染患者的临床分离株进行测序，描述了CZA耐药性的演变。
在本研究中，从一名脑出血后CRKP感染患者的痰液和血液样本中分离出6株CRKP菌株。选择其中2株进行全基因组分析。
药敏试验显示，CZA治疗6天后分离出的CRKP菌株对CZA的最低抑菌浓度（MIC）比CZA治疗前分离出的3株CRKP菌株高64倍（4 vs >256 μg/mL），而亚胺培南和美罗培南的MIC相对分别降低了128倍（>32 vs 0.25 μg/mL）和16倍（> 32 vs 2 μg/mL）。多位点序列分型显示，从该患者分离出的所有6株CRKP菌株均为ST11，脉冲场凝胶电泳证实它们属于同一克隆。选择2株进行全基因组分析。耐药菌株中Ω环第179位的天冬氨酸残基被酪氨酸残基取代，质粒发生了 到 的突变。改良碳青霉烯灭活法以及碳青霉烯酶抑制剂增强和胶体金酶免疫层析法检测 的结果均为阴性。
这是河南的首例报告，表明CZA治疗6天可导致突变并使表型从CZA敏感变为耐药。因此，在CZA治疗期间应常规进行药敏试验和碳青霉烯酶表型检测，基因型测定至关重要。
