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“数小时内即可得出结果”:一项使用纳米孔测序进行胆管培养的前瞻性临床研究。

"Answers in hours": A prospective clinical study using nanopore sequencing for bile duct cultures.

机构信息

Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN.

Division of Surgical Research, Department of Surgery; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN.

出版信息

Surgery. 2022 Mar;171(3):693-702. doi: 10.1016/j.surg.2021.09.037. Epub 2021 Dec 29.

DOI:10.1016/j.surg.2021.09.037
PMID:34973809
Abstract

BACKGROUND

Surgical site infection is a major source of morbidity in patients undergoing pancreatic head resection and is often from organisms in intraoperative bile duct cultures. As such, many institutions use prolonged prophylactic antibiotics and tailor based on bile duct cultures. However, standard cultures take days, leaving many patients unnecessarily on prolonged antibiotics. Nanopore sequencing can provide data in hours and, thus, has the potential to improve antibiotic stewardship. The present study investigates the feasibility of nanopore sequencing in intraoperative bile samples.

METHODS

Patients undergoing pancreatic head resection were included. Intra-operative bile microbial profiles were determined with standard cultures and nanopore sequencing. Antibiotic recommendations were generated, and time-to-results determined for both methods. Organism yields, resistance patterns, antibiotic recommendations, and costs were compared.

RESULTS

Out of 42 patients, 22 (52%) had samples resulting in positive standard cultures. All positive standard cultures had microbes detected using nanopore sequencing. All 20 patients with negative standard cultures had negative nanopore sequencing. Nanopore sequencing detected more bacterial species compared to standard cultures (10.5 vs 4.4, p < 0.05) and more resistance genotypes (10.3 vs 2.7, p < 0.05). Antimicrobial recommendations based on nanopore sequencing provided coverage for standard cultures in 27 out of 44 (61%) samples, with broader coverage recommended by nanopore sequencing in 13 out of 27 (48%) of these samples. Nanopore sequencing results were faster (8 vs 98 hours) than standard cultures but had higher associated costs ($165 vs $38.49).

CONCLUSION

Rapid microbial profiling with nanopore sequencing is feasible with broader organism and resistance profiling compared to standard cultures. Nanopore sequencing has perfect negative predictive value and can potentially improve antibiotic stewardship; thus, a randomized control trial is under development.

摘要

背景

手术部位感染是接受胰头切除术患者发病率的主要来源,通常来自术中胆管培养物中的微生物。因此,许多机构使用延长的预防性抗生素,并根据胆管培养物进行调整。然而,标准培养需要数天时间,导致许多患者不必要地长期使用抗生素。纳米孔测序可以在数小时内提供数据,因此有可能改善抗生素管理。本研究调查了术中胆汁样本中纳米孔测序的可行性。

方法

纳入接受胰头切除术的患者。使用标准培养和纳米孔测序确定术中胆汁微生物谱。生成抗生素建议,并确定两种方法的结果时间。比较了生物体产量、耐药模式、抗生素建议和成本。

结果

在 42 名患者中,有 22 名(52%)患者的样本培养出阳性标准培养物。所有阳性标准培养物均通过纳米孔测序检测到微生物。所有 20 名标准培养物阴性的患者的纳米孔测序均为阴性。与标准培养物相比,纳米孔测序检测到更多的细菌种类(10.5 比 4.4,p < 0.05)和更多的耐药基因型(10.3 比 2.7,p < 0.05)。基于纳米孔测序的抗生素建议在 44 个样本中的 27 个(61%)提供了标准培养物的覆盖范围,在这 27 个样本中的 13 个(48%)中提供了更广泛的覆盖范围。纳米孔测序的结果比标准培养物更快(8 小时比 98 小时),但相关成本更高(165 美元比 38.49 美元)。

结论

与标准培养物相比,纳米孔测序快速微生物分析具有更广泛的生物体和耐药性分析,是可行的。纳米孔测序具有完美的阴性预测值,有可能改善抗生素管理;因此,正在开展一项随机对照试验。

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