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重症免疫功能正常患者的巨细胞病毒再激活

Cytomegalovirus reactivation in critically ill immunocompetent patients.

作者信息

Limaye Ajit P, Kirby Katharine A, Rubenfeld Gordon D, Leisenring Wendy M, Bulger Eileen M, Neff Margaret J, Gibran Nicole S, Huang Meei-Li, Santo Hayes Tracy K, Corey Lawrence, Boeckh Michael

机构信息

Department of Laboratory Medicine, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA 98195-7110, USA.

出版信息

JAMA. 2008 Jul 23;300(4):413-22. doi: 10.1001/jama.300.4.413.

Abstract

CONTEXT

Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined.

OBJECTIVE

To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons.

DESIGN, SETTING, AND PARTICIPANTS: We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models.

MAIN OUTCOME MEASURES

Association of CMV reactivation with prolonged hospital length of stay or death.

RESULTS

The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log(10) copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days.

CONCLUSIONS

These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.

摘要

背景

巨细胞病毒(CMV)感染与免疫抑制患者的不良临床结局相关,但在缺乏免疫抑制证据的重症患者中,CMV再激活的发生率及其与不良结局的关联尚未明确界定。

目的

确定CMV再激活与重症免疫功能正常患者的重症监护病房(ICU)住院时间及住院总时长之间的关联。

设计、地点和参与者:我们前瞻性地通过每三周一次的实时聚合酶链反应(PCR)评估了120名CMV血清学阳性、免疫功能正常的成年患者的血浆CMV DNA血症,并观察其临床结局。这些患者于2004年至2006年期间被收治入美国一家大型三级医疗学术医学中心的2家不同医院的6个ICU中的1个。临床测量由对CMV PCR结果不知情的人员进行评估。通过多变量逻辑回归和比例优势模型评估CMV再激活的危险因素及其与住院和ICU住院时长的关联。

主要结局指标

CMV再激活与延长的住院时长或死亡之间的关联。

结果

120名患者中有45名(35%)在30天时出现持续住院(n = 35)或死亡(n = 10)的主要复合终点。任何水平的CMV病毒血症发生率为33%(39/120;95%置信区间[CI],24% - 41%),中位时间为12天(范围,3 - 57天);CMV病毒血症大于1000拷贝/mL的发生率为20%(24/120;95% CI,13% - 28%),中位时间为26天(范围,9 - 56天)。通过逻辑回归分析,任何水平的CMV感染(调整优势比[OR],4.3;95% CI,1.6 - 11.9;P = 0.005)、大于1000拷贝/mL的CMV感染(调整OR,13.9;95% CI,3.2 - 60;P < 0.001)以及以每毫升log(10)拷贝数计算的CMV曲线下平均面积(AUC)(调整OR,2.1;95% CI,1.3 - 3.2;P < 0.001)均与30天时的住院或死亡独立相关。在多变量部分比例优势模型中,CMV 7天移动平均值(OR,5.1;95% CI,2.9 - 9.1;P < 0.001)和CMV AUC(OR,3.2;95% CI,2.1 - 4.7;P < 0.001)均与至少14天的住院时长独立相关。

结论

这些初步研究结果表明,CMV再激活在重症免疫功能正常患者中频繁发生,且与住院时间延长或死亡相关。在此情况下进行CMV预防的对照试验是必要的。

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