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实体器官移植受者诺卡菌病的危险因素及预防:一项巢式病例对照研究。

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case-control study.

作者信息

Yetmar Zachary A, Chesdachai Supavit, Duffy Dustin, Smith Byron H, Challener Douglas W, Seville Maria Teresa, Bosch Wendelyn, Beam Elena

机构信息

Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA.

出版信息

Clin Transplant. 2023 Sep;37(9):e15016. doi: 10.1111/ctr.15016. Epub 2023 May 11.

Abstract

BACKGROUND

Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis.

METHODS

We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients.

RESULTS

One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35).

CONCLUSIONS

Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

摘要

背景

诺卡菌是一种机会致病菌,主要影响免疫功能低下的个体,包括实体器官移植(SOT)受者。高达2.65%的SOT受者会发生诺卡菌病;然而,很少有研究探讨诺卡菌病的危险因素和预防措施。

方法

我们对2000年至2020年期间成年SOT受者中经培养确诊为诺卡菌病的患者进行了一项多中心、匹配的巢式病例对照研究。对照按性别、首次移植器官、移植年份、移植中心和移植后充分随访情况以2:1的比例进行匹配。采用多变量条件逻辑回归分析与诺卡菌病的相关性。采用Cox比例风险回归比较感染患者和未感染患者的12个月死亡率。

结果

123例SOT受者与245例未感染对照进行了匹配。钙调神经磷酸酶抑制剂水平升高、急性排斥反应、巨细胞病毒感染、淋巴细胞减少、泼尼松剂量较高和年龄较大与诺卡菌病显著相关,而甲氧苄啶-磺胺甲恶唑预防具有保护作用(比值比[OR]0.34;95%置信区间[CI]0.13 - 0.84)。在仅包括每周给药超过两次的预防措施的敏感性分析中,或限于2015 - 2020年的分析中,预防措施的效果相似,尽管并非总是具有统计学意义(OR 0.30;95% CI 0.11 - 0.80)或(OR 0.33,95% CI 0.09 - 1.21)。诺卡菌病与12个月死亡率增加相关(风险比5.47;95%置信区间2.42 - 12.35)。

结论

多种免疫抑制措施以及缺乏甲氧苄啶-磺胺甲恶唑预防与SOT受者的诺卡菌病相关。预防措施的有效性可能与甲氧苄啶-磺胺甲恶唑的剂量或频率有关。在免疫抑制增强或免疫功能低下迹象明显的SOT受者中,应优先使用甲氧苄啶-磺胺甲恶唑而非其他替代药物。

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