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全基因组测序确诊免疫功能低下患者由乔治西里亚星诺卡菌引起的播散性感染

Disseminated Infection Caused by Nocardia cyriacigeorgica in Immunocompromised Patient Confirmed by Whole Genome Sequencing.

作者信息

Varda Brkić Dijana, Babel Jakša, Budimir Ana, Butić Iva, Gužvinec Marija, Jurić Dragan, Ferenčak Ivana, Bošnjak Selma, Mareković Ivana

机构信息

Clinical Department of Clinical Microbiology, Infection Prevention and Control, University Hospital Centre Zagreb, Zagreb, Croatia.

Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.

出版信息

Chemotherapy. 2025;70(1):1-8. doi: 10.1159/000539977. Epub 2024 Aug 10.

Abstract

INTRODUCTION

Nocardia spp. is an opportunistic pathogen capable of causing localized and disseminated infections in immunocompromised hosts. It is critical for serious infections to have an early and accurate identification of this pathogen in order to enable timely and focused combination antimicrobial treatment.

CASE PRESENTATION

We describe the case of an 87-year-old patient previously treated for myasthenia gravis with corticosteroids and azathioprine. Patient was admitted at the emergency department with clinical signs of sepsis with cellulitis of right hand associated with injury acquired after gardening and trimming roses and did not respond to empirical antimicrobial treatment. Computerized tomography revealed pulmonary infiltrates with inflammatory etiology. Nocardia cyriacigeorgica was cultivated from blood culture, skin swab, abscess aspirate, and endotracheal aspirate and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing, and whole genome sequencing (WGS). Susceptibility testing was performed with E-test (bioMerieux, Marcy-l'Étoile, France), and corresponding resistance genes were detected by WGS. Resistance to amoxicillin-clavulanate, azithromycin, ciprofloxacin, and vancomycin was detected by both methods. Despite all interventions and the patient receiving antimicrobial treatment including imipenem-cilastatin, amikacin, and trimethoprim-sulfamethoxazole, the course and outcome of infection were unfavorable.

CONCLUSION

We would like to emphasize the need to consider the possibility of disseminated Nocardia infection in immunocompromised patients, especially in patients receiving long-term corticosteroid treatment with skin infections and/or cavitary lung lesions, especially if these do not improve with standard antimicrobial treatment. Precise species identity provides a critical guide for physicians in the choice of targeted treatment. Thanks to MALDI-TOF MS, Nocardia spp. identification is now available in routine lab work. WGS is still inevitable for the identification of uncommon and novel species due to the high sequence similarities between closely related species and the genetic diversity of that genus.

摘要

引言

诺卡菌属是一种机会致病菌,能够在免疫功能低下的宿主中引起局部和播散性感染。对于严重感染而言,早期准确鉴定这种病原体至关重要,以便能够及时进行有针对性的联合抗菌治疗。

病例报告

我们描述了一名87岁患者的病例,该患者曾用皮质类固醇和硫唑嘌呤治疗重症肌无力。患者因败血症临床症状、右手蜂窝织炎伴园艺修剪玫瑰后受伤而入住急诊科,经验性抗菌治疗无效。计算机断层扫描显示肺部有炎症性病因的浸润影。从血培养、皮肤拭子、脓肿抽吸物和气管内抽吸物中培养出乔治西里亚基诺卡菌,并通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)、16S rRNA测序和全基因组测序(WGS)进行鉴定。使用E-test(法国马赛-埃托瓦勒生物梅里埃公司)进行药敏试验,并通过WGS检测相应的耐药基因。两种方法均检测到对阿莫西林-克拉维酸、阿奇霉素、环丙沙星和万古霉素耐药。尽管采取了所有干预措施,且患者接受了包括亚胺培南-西司他丁、阿米卡星和甲氧苄啶-磺胺甲恶唑在内的抗菌治疗,但感染的病程和结局仍不理想。

结论

我们想强调,需要考虑免疫功能低下患者发生播散性诺卡菌感染的可能性,尤其是接受长期皮质类固醇治疗且有皮肤感染和/或空洞性肺部病变的患者,特别是如果这些病变在标准抗菌治疗下没有改善。精确的菌种鉴定为医生选择靶向治疗提供了关键指导。多亏了MALDI-TOF MS,现在常规实验室工作中可以进行诺卡菌属的鉴定。由于密切相关菌种之间的高序列相似性以及该属的遗传多样性,对于罕见和新菌种的鉴定,WGS仍然是必不可少的。

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