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肺移植受者中诺卡菌感染的预防、治疗和结局:一项匹配病例对照研究。

Nocardia prophylaxis, treatment, and outcomes of infection in lung transplant recipients: A matched case-control study.

机构信息

Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Glendale, AZ, USA.

Division of Transplant Pulmonology, Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

出版信息

Transpl Infect Dis. 2021 Apr;23(2):e13478. doi: 10.1111/tid.13478. Epub 2020 Oct 13.

Abstract

BACKGROUND

Lung transplant recipients are at heightened risk for nocardiosis compared to other solid organ transplant recipients, with incidence rates as high as 9% and up to 30% associated mortality. No controlled studies assessing risk factors for nocardiosis in this high-risk population have been reported.

METHODS

Patients undergoing lung transplantation at a single center between 2012 and 2018 and diagnosed with nocardiosis post-transplant were matched 1:2 to uninfected control subjects on the basis of age, transplant date, and sex.

RESULTS

The incidence of nocardiosis in this lung transplant population was 3.4% (20/586), occurring a median of 9.4 months (range 4.4-55.2) post-transplant. In multivariable analysis, consistent use of trimethoprim/sulfamethoxazole (TMP/SMX) in the 12 weeks prior to diagnosis was independently associated with protection against nocardiosis (OR 0.038; 95% CI 0.01-0.29; P = .002). Augmented immunosuppression in the 6 months prior to diagnosis was independently associated with the development of nocardiosis (OR 9.94; 95% CI 1.62- 61.00; P = .013). Six case patients (30%) had disseminated disease; all-cause 6-month mortality was 25%. The most common species was Nocardia farcinica (7/17 isolates), which was associated with dissemination and mortality. The most active antibiotics were TMP/SMX (100%), linezolid (100%), and amikacin (76%). Imipenem was only active against 4/17 isolates (24% susceptibility), with two isolates becoming non-susceptible later in therapy.

CONCLUSIONS

Trimethoprim/sulfamethoxazole prophylaxis was shown to be protective against nocardiosis in lung transplant recipients, while augmented immunosuppression conferred increased risk. Institutional epidemiologic data are needed to best guide empiric therapy for Nocardia, as historical in vitro data may not predict local susceptibilities.

摘要

背景

与其他实体器官移植受者相比,肺移植受者罹患诺卡氏菌病的风险更高,发病率高达 9%,死亡率高达 30%。目前尚未报道在这一高危人群中评估诺卡氏菌病危险因素的对照研究。

方法

本研究对 2012 年至 2018 年在单中心接受肺移植且术后确诊为诺卡氏菌病的患者进行了回顾性队列研究,并根据年龄、移植日期和性别与未感染对照患者 1:2 匹配。

结果

在该肺移植人群中,诺卡氏菌病的发病率为 3.4%(20/586),中位发病时间为移植后 9.4 个月(范围 4.4-55.2)。多变量分析显示,在诊断前 12 周持续使用复方磺胺甲噁唑(TMP/SMX)与诺卡氏菌病的发生呈独立负相关(比值比 0.038;95%可信区间 0.01-0.29;P=0.002)。在诊断前 6 个月内增强免疫抑制与诺卡氏菌病的发生呈独立正相关(比值比 9.94;95%可信区间 1.62-61.00;P=0.013)。6 例患者(30%)发生播散性疾病;全因 6 个月死亡率为 25%。最常见的菌种是星形诺卡氏菌(17 株分离株中的 7 株),与播散性疾病和死亡率相关。最有效的抗生素是复方磺胺甲噁唑(100%)、利奈唑胺(100%)和阿米卡星(76%)。亚胺培南仅对 17 株分离株中的 4 株(4 株的敏感性为 24%)有效,其中 2 株在治疗过程中对药物的敏感性降低。

结论

复方磺胺甲噁唑预防可降低肺移植受者发生诺卡氏菌病的风险,而增强免疫抑制则增加了发病风险。需要机构流行病学数据来最佳指导诺卡氏菌经验性治疗,因为历史体外数据可能无法预测当地的敏感性。

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