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病例报告:关于一例肺移植术后高氨血症综合征:宏基因组下一代测序能否改善临床管理?

Case Report: About a Case of Hyperammonemia Syndrome Following Lung Transplantation: Could Metagenomic Next-Generation Sequencing Improve the Clinical Management?

作者信息

Michel Charlotte, Raimo Michela, Lazarevic Vladimir, Gaïa Nadia, Leduc Nina, Knoop Christiane, Hallin Marie, Vandenberg Olivier, Schrenzel Jacques, Grimaldi David, Hites Maya

机构信息

Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.

Clinic of Infectious Diseases, Cliniques Universitaires de Bruxelles, Erasme Hospital, Brussels, Belgium.

出版信息

Front Med (Lausanne). 2021 Jul 6;8:684040. doi: 10.3389/fmed.2021.684040. eCollection 2021.

Abstract

and spp. are responsible for opportunistic infections in transplant patients, sometimes causing a life-threatening hyperammonemia syndrome. Both pathogens are not identified with standard microbiology techniques, resulting in missed or delayed diagnosis. We present a clinical case that illustrates the added value that next-generation sequencing (NGS) may offer in the diagnosis of respiratory infections in immune-compromised patients. A 55 years-old man with idiopathic pulmonary fibrosis underwent double lung transplantation. He received antibiotic prophylaxis with piperacillin-tazobactam and azythromycin. At day 4 post-transplantation (PTx), the patient presented an acute respiratory distress. A broncho-alveolar lavage (BAL) was performed. At day 5 PTx, the patient presented a status epilepticus due to diffuse cerebral oedema. Serum ammonia concentration was 661 μg/dL. BAL bacterial culture was negative. Because of the clinical presentation, special cultures were performed and identified 100.000 CFU/mL of and spp. and specific PCRs were positive for and . Antibiotic therapy was shifted to therapeutic dose of azithromycin and doxycycline; within 48 h ammonia serum concentrations returned to normal but the coma persisted several weeks, followed by a persistent frontal lobe syndrome. A follow-up BAL was performed on day 11 Ptx. The culture was negative, yet the specific PCRs remained positive. Bacterial culture found 100 CFU/mL of and viral culture was positive for Herpes Simplex Virus-1. These results were confirmed by metagenomic next-generation sequencing (mNGS). In the bacterial fraction, the majority of reads belonged to (34.7%), (24.1%) and (17.1%). Reads assigned to and represented 0.71, 0.13, and 0.04% of the bacterial fraction and corresponded to 6.9 × 10, 9.7 × 10, and 3.7 × 10 genome equivalents per mL of BAL fluid, respectively. These results are in favor of a cure of the atypical infection. mNGS offered added diagnostic and quantitative values compared to PCR tests, which can remain positive after resolved infections. The initiation of appropriate antibiotic therapy would have occurred earlier on, possibly resulting in a better clinical outcome if mNGS had been performed in a routine fashion.

摘要

[病原体名称]和[病原体名称]属导致移植患者发生机会性感染,有时会引发危及生命的高氨血症综合征。这两种病原体无法通过标准微生物学技术鉴定出来,从而导致诊断延误或漏诊。我们报告了一例临床病例,该病例说明了下一代测序(NGS)在免疫功能低下患者呼吸道感染诊断中可能具有的附加价值。一名55岁的特发性肺纤维化男性患者接受了双肺移植。他接受了哌拉西林 - 他唑巴坦和阿奇霉素的抗生素预防治疗。移植后第4天(PTx),患者出现急性呼吸窘迫。进行了支气管肺泡灌洗(BAL)。移植后第5天,患者因弥漫性脑水肿出现癫痫持续状态。血清氨浓度为661μg/dL。BAL细菌培养结果为阴性。鉴于临床表现,进行了特殊培养,鉴定出每毫升含有100,000 CFU的[病原体名称]和[病原体名称]属,且针对[病原体名称]和[病原体名称]的特异性PCR检测呈阳性。抗生素治疗改为阿奇霉素和强力霉素的治疗剂量;48小时内血清氨浓度恢复正常,但昏迷持续了数周,随后出现持续性额叶综合征。移植后第11天进行了随访BAL。[病原体名称]培养结果为阴性,但特异性PCR检测仍为阳性。细菌培养发现每毫升含有100 CFU的[病原体名称],病毒培养显示单纯疱疹病毒1型呈阳性。这些结果通过宏基因组下一代测序(mNGS)得到了证实。在细菌组分中,大多数读数属于[病原体名称](34.7%)、[病原体名称](24.1%)和[病原体名称](17.1%)。分配给[病原体名称]和[病原体名称]的读数分别占细菌组分的0.71%、0.13%和0.04%,分别对应每毫升BAL液中6.9×10、9.7×10和3.7×10个基因组当量。这些结果表明非典型感染已治愈。与PCR检测相比,mNGS提供了额外的诊断和定量价值,PCR检测在感染消除后可能仍呈阳性。如果以常规方式进行mNGS检测,可能会更早开始适当的抗生素治疗,从而可能带来更好的临床结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a857/8290067/045e95e95f0c/fmed-08-684040-g0001.jpg

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