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IF 2 3区医学 Q2 PEDIATRICS

BMC Pediatrics Pub Date : 2025-02-04 DOI:10.1186/s12887-025-05389-y

Jian Zhou, Jingqian Zhou, Min Chen, Pan Lü, Chunming Jiang

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引用次数: 0

摘要

导言：大肠埃希氏菌（E. coli）是新生儿重症监护室（NICU）中新生儿感染的原因。虽然β-内酰胺类抗生素是治疗新生儿感染性疾病的常用药物，但大肠埃希菌对这些药物具有耐药性。因此，我们研究了从新生儿重症监护室分离的大肠杆菌菌株对β-内酰胺类抗生素的耐药性：方法：从 2020 年至 2023 年期间入住新生儿重症监护室的患者中收集大肠杆菌分离株。分析了患者的临床特征。采用琼脂稀释法测定大肠埃希菌的抗菌药敏感性，并利用 PCR 分析其 β-内酰胺酶基因的分布情况。通过共轭实验分析了质粒上抗性基因的水平转移性。提取基因组 DNA 进行全基因组测序，构建质粒物理图谱，定位抗性基因，分析侧翼区和抗性基因相关序列：结果：在整个研究期间，共收集到 110 株不同的大肠杆菌。结果：在整个研究期间，共收集到 110 株不同的大肠埃希氏菌株，其中 62 个病例的菌株对 7 种ß-内酰胺类抗生素中的至少一种产生耐药性，这些病例与呼吸机相关性肺炎（35/62）、导管相关性尿路感染（14/62）、坏死性小肠结肠炎（7/62）、皮肤感染（1/62）和新生儿败血症（5/62）等疾病相关。大肠杆菌分离株对七种 β-内酰胺类抗生素的耐药性从 2.73% 到 56.36%不等。在 62 株菌株（56.36%，62/110）中，发现了 111 个 β-内酰胺酶基因中的 6 个基因型（11 个亚基因型）。共轭实验发现两株携带 blaKPC-2 基因的转共轭物和两株携带 blaOXA-1 基因的转共轭物对碳青霉烯类和其他 β-内酰胺类药物具有抗性。四株菌株的质粒成功共轭并转入受体大肠杆菌 C600。转共轭抗性基因的聚合酶链式反应（PCR）显示，其中两株携带 blaKPC-2 基因，其 MIC 相对于受体提高了 32 倍，另外两株携带 blaOXA-1 基因，其 MIC 提高了 32 倍。对于携带 blaKPC-2、blaCTX-M-64、blaCTX-M-65 和 blaTEM-1 的分离物 ECK03，测序结果表明 blaKPC-2、blaCTX-M-64 和 blaTEM-1 包藏在一个 114-kb pECK03_KPC-2 质粒上，而两个相同的 blaCTX-M-64 基因则包藏在大肠杆菌分离物 ECF13 中。结论：这些发现突显了新生儿重症监护病房人群中存在大肠杆菌的β-内酰胺耐药性，强调了持续监控β-内酰胺酶分离物的必要性，以促进有效的抗生素选择。

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Prevalence of β-lactam antibiotic resistance of Escherichia coli isolated from a neonatal intensive care unit.

Introduction: Escherichia coli (E. coli) causes infections in neonates admitted to neonatal intensive care units (NICUs). Although β-lactam antibiotics are commonly used for neonatal infectious diseases, E. coli has exhibited resistance to them. Therefore, we investigated the resistance of E. coli strains isolated from a NICU to β-lactam antibiotics.

Methods: E. coli isolates were collected from patients admitted to a NICU from 2020-2023. The clinical characteristics of the patients were analyzed. The antimicrobial susceptibility was determined using the agar dilution method, and the distribution of β-lactamase genes was analyzed using PCR. Conjugation experiments were conducted to analyze the horizontal transferability of resistance genes on plasmids. Genomic DNA was extracted for whole genome sequencing, construction of plasmid physical maps, locating resistance genes, and analyzing flanking regions and the resistance gene-related sequences.

Results: Throughout the study period, 110 distinct E. coli strains were collected. Among these, 62 cases presented strains, which were resistant against at least one of seven ß-lactam antibiotics associated with conditions such as ventilator-associated pneumonia (35/62), catheter-associated urinary tract infection (14/62), necrotizing enterocolitis (7/62), skin infection (1/62), and neonatal septicemia (5/62). Resistance of E. coli isolates to seven β-lactam antibiotics ranged from 2.73-56.36%. In 62 strains (56.36%, 62/110), six genotypes (11 sub-genotypes) of 111 β-lactamase genes were identified. Conjugation experiments revealed two transconjugants carrying the bla_KPC-2 gene and two carrying the bla_OXA-1 gene, exhibiting resistance to carbapenems and other β-lactams. The plasmids of four strains were successfully conjugated and transferred to recipient E. coli C600. PCR of the transconjugant resistance genes revealed that two carried a bla_KPC-2 gene with a MIC increased up to 32-fold relative to the recipients, and the other two carried a bla_OXA-1 gene with a 32-fold increased MIC. For isolate ECK03 carrying bla_KPC-2, bla_CTX-M-64, bla_CTX-M-65, and bla_TEM-1, sequencing results showed that bla_KPC-2, bla_CTX-M-64, and bla_TEM-1 were harbored on a 114-kb pECK03_KPC-2 plasmid, whereas two identical bla_CTX-M-64 genes were harbored in E. coli isolate ECF13. CONCLUSION: These findings highlight the existence of E. coli β-lactam resistance within NICU populations, emphasizing the need for continual monitoring of β-lactamase isolates to facilitate effective antibiotic selection.

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来源期刊

BMC Pediatrics PEDIATRICS-

CiteScore

3.70

自引率

4.20%

发文量

683

审稿时长

3-8 weeks

期刊介绍： BMC Pediatrics is an open access journal publishing peer-reviewed research articles in all aspects of health care in neonates, children and adolescents, as well as related molecular genetics, pathophysiology, and epidemiology.