血清降钙素原水平(翻译稿)

1、Serum Procalcitonin LevelsIt Is All About ConfidenceAlbrich and colleagues1 successfully orchestrated an observational, multinational, multicenter, prospective study of the influence of serum procalcitonin (PCT) levels on the care of patients with lower respiratory tract infections (LRTIs). Specific

2、ally, does access to PCT levels plus the use of an interpretative advice algorithm influence the duration of antibiotic therapy? The comparison was between patients whose physicians were compliant with the algorithm vs patients whose physicians were noncompliant. Noncompliance was defined as failure

3、 to follow the algorithm by either initiation of antibiotic therapy or failure to discontinue therapy despite low PCT levels in the absence of predefined criteria that allowed the algorithm to be overruled. In short, the algorithm advice was overruled and managed based on clinical judgment.The prima

4、ry end point was duration of antibiotic therapy. Of 1208 patients who received at least 1 dose of an antibiotic, the mean duration of therapy was 5.9 days when the algorithm was followed and 7.4 days (P<.001) when physicians did not comply with the algorithm. The shorter duration stood the test o

5、f multivariable analyses looking for confounders; of course, some important confounder may have been missed.Of interest, algorithm compliance was substantively better in those centers that had participated in earlier PCT studies. I suggest that algorithm compliance, or lack thereof, is a direct refl

6、ection of the confidence level of physicians in the interpretation of the meaning of serum PCT levels.The study by Albrich et al1 is the latest of several studies of patients with LRTIs and PCT treatment guidance. In most studies, compliance with the PCT algorithm shortened the duration of antibioti

7、c therapy.2,3 Nonetheless, a healthy skepticism persists. Critics worry about the specificity of an increase in PCT levels for bacterial as opposed to viral infection. Physicians wonder what happens to serum PCT levels if there is dual infection, eg, pneumonia due to Streptococcus pneumoniae concomi

8、tant with influenza tracheobronchitis. Why dose the serum PCT level increase in patients after aortocoronary bypass surgery or in patients with cardiogenic shock? In short, does the serum PCT level help the clinician beyond the usual markers of activation of an innate immune response, ie, erythrocyt

9、e sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell and differential counts?With the caveat that we need a lot more information, the emerging data suggest that PCT levels add value. Like ESR and CRP, PCT is part of the early phases of an innate immune response. A virtue of PCT

10、 levels is that they increase within 4 to 6 hours of initiation of bacterial infection or intravenous endotoxin, while increases in CRP level and ESR require 24 or more hours.4,5Serum PCT levels do not increase substantively after uncomplicated viral respiratory tract infections (RTIs). The mechanis

11、m is believed to be viral-induced increases in g-interferon, which in turn represses PCT gene reanscription.6 Retrospective studies of children with RTIs indicate little to no increase in serum PCT levels in response to viral or mycoplasma infection.7 Note also that serum PCT levels increased in pat

12、ients with bacterial meningitis but did not increase in patients with viral meningitis.8 Clearly, there is an urgent need to use the powerful modern tools of molecular diagnostics in patients of all ages with RTIs to establish a more definite microbial etiology (perhaps mixed pathogen etiology) of t

13、he RTI and correlate the results with serum PCT levels.Confidence in PCT levels would also be enhanced if the basic biology was better understood. In vitro, PCT synthesis is stimulated by bacterial lipopolysaccharide (endotoxin), tumor necrosis factor, and interleukin 1.4-6 Of interest, the magnitud

14、e of PCT production was greater in patients with bacteremia due to gram-negative bacteria as opposed to bacteremia with gram-positive bacteria.9 This observation is pertinent to clinical low intestinal perfusion states that are associated with elevations in serum PCT levels.Bacterial endotoxin is de

15、tectable in human serum during and after aortocoronary bypass surgery.10 Bacterial endotoxin is detectable in human serum in profound cardiogenic shock, some general surgery patients, patients with severe pancreatitis, and other patients with poor perfusion of the mucosa of the intestinal tract.4,10

16、 The supposition is that the gut bacteria “translocate” into the submucosa and then to the bloodstream with concomitant elevation of PCT levels as a market of activation of an innate immune response.Understanding the science will increase confidence. However, for serum PCT levels to influence patien

17、t care, the clinician needs the PCT result at point of care. Similar to white blood cell count, it is strongly suggested that, if offered, serum PCT levels should be available at all times with results within 1 hour of receipt of serum in the laboratory. The prompt report of a low PCT level, within

18、the context of the rest of the clinical assessment, could influence the decision to start, continue, or discontinue antibiotic therapy.In the study by Albrich et al,1 compliance with the PCT algorithm in the participating US hospital was only 35%. Compliance would surely increase if physicians had m

19、ore confidence in their understanding of the factors that drive an increase or decrease of serum PCT levels. David Gilbert, MD1. Albrich WC, Dusemund F, Bucher B, et al. Effectiveness and safety of procalcitonin-guided antibiotic therapy in lower respiratory tract infections in “real life”: an inter

20、national, multicenter post-study survey (ProREAL). Arch Intern Med. 2012;172(9):715-722.2. Li H, Luo Y=F, Blackwell TS, Xie C-M. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections. Antimicrob Agent Chemother. 2011;55(12):5900-5906.3. Schuetz P, Chiapp

21、a V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322-1331.4. Becker KL, Nylen ES, White JC, Muller B, Snider RHJr. Clinical review 167

22、: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab. 2004;89(4)1512-1525.5. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: cli

23、nical utility and limitations. Crit Care Med. 2008;36(3):941-952.6. Linscheid P, Seboek D, Nylen ES, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells : a novel product of human adipose tissue. Endocrinology. 2003;144(12):5578-5584.7. Schutzle H, Forster J, Superti-F

24、urga A, Berner R. Is serum procalcitonin a reliable disgnostic marker in children with acute respiratory tract infections? a retrospective analysis. Eur J Pediatr. 2009;168(9):1117-1124.8. Schwarz S, Bertram M, Schwab S, Andrassy K, Hacke W. Serum procalcitonin levels in bacterial and abacterial men

25、ingitis. Crit Care Med. 2000;28(6):1828-1832.9. Charles PE, Ladoire S, Aho S, et al. Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either Gram negative or Gram positive bacteria. BMC Infect Dis. 2008;8:38=46.10. Patham N, Burmester M, Adamovic T, et al

26、. Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease. Am J Respir Crit Care Med. 2011;184(11):1261-1269.血清降钙素原水平一切和信心相关内科医学档案2012年5月14日172卷9号P722-723 Albrich和同事们通过精心策划，成功进行了一个可观测的跨国多中心的前瞻性研究，即血清降钙素原水平对关怀病人而降低下呼吸道感染的影响研究。具体说，降钙素原水平通道会增加一个解释性的规则建议从而抗生素疗法的持续时间

27、吗？这个比较只是针对那些规则遵从性主治医生的病人与非规则遵从性主治医生的病人。非规则遵从性是在抗生素疗法一开始就没能根据规则进行治疗的或是在缺乏预判标准的前提下尽管降钙素原水平偏低却没能中止治疗的情况等，都属于规则无效。简而言之，运算法则已宣布无效并只能设法根据临床诊断而判断。 最早的终点在于抗生素疗法的持续时间。在1208例接受了至少1剂抗生素的病人中，根据运算规则进行的话平均持续时间需要5.9天；而医生没有按照预算规则进行的话则需要7.4天(P<.001)。当然，试验中较短的持续时间维持需要共同创始人的多变量分析，而一些重要的创始人也有可能被漏掉。 有趣的是，那些曾经参与过早期降钙素

28、原研究的中心在规则遵循上实际要好。笔者建议规则遵循，或是缺乏规则遵循，会直接反应医生在解释血清降钙素原水平意义上的信心。 在数个类似的研究中，Albrich等人的研究是下呼吸道感染和血清降钙素原治疗病人的指导上市最新的。许多的研究中，遵循血清降钙素原原则缩短了抗生素疗法的疗程。尽管如此，我们仍需要有一个合理的怀疑态度。批评者担心在细菌的血清降钙素原水平特异性的增加与病毒感染正好相反。医生们想看看如果存在双倍的感染血清降钙素原水平会发生怎样的变化，比如说，急性肺炎病源是由于链球菌肺炎伴随流行性感冒支气管炎。病人在主动脉冠状动脉分流术手术后或有急性心肌炎的情况下血清降钙素原水平上升的原因何在？简而

29、言之，血清降钙素原水平堆临床医生在超出固有免疫反应通常的活化特征中会有帮助吗？如红细胞沉淀率(erythrocyte sedimentation rate， ESR)，C-反应蛋白(C-reactive protein， CRP)，以及白细胞和不同的计数方面等。 对于这样的警告我们需要大量更多的信息，新兴的数据提示血清降钙素原水平价值增加。像对红细胞沉淀率和C-反应蛋白来说，血清降钙素原只是固有免疫反应早期表述的一部分。血清降钙素原水平的长处之一即它们能在4至6小时内增强细菌感染或静脉注射内毒素的起始作用，而增强C-反应蛋白的水平和红细胞沉淀率则需要24小时或者更多的时间。 事实上，血清降钙素

30、原水平在无合并症病毒性呼吸道感染下并不会增强。这种机制被认为是g-感染中病毒诱导的增加，其反过来会抑制降钙素原基因的复制。对患有呼吸道感染儿童的可追溯性研究基本不能暗示血清降钙素原水平在对病毒性或支原体感染反应中没有增强。还需强调的是细菌性脑膜炎患者的血清降钙素原水平会增强，而病毒性脑膜炎患者则不会。显然，这样的结论急切需要使用强有力的现代化分子诊断工具对所有年龄段呼吸道感染病患者进行诊断的支撑，从而建立一个更完整的呼吸道感染的微生物病因学（也许是混合型病原体病因学）及纠正血清降钙素原水平的结果。 如果对基本的生物学有一个更好的理解，那么对血清降钙素原水平的信心也会增强。在试管中，降钙素原合成

31、是通过刺激细菌脂多糖（内毒素），肿瘤坏疽因素，和白细胞介素1。有趣的是，巨大的降钙素原产物对患革兰氏阴性菌血症患者的作用大于革兰氏阳性菌血症患者。这一观察有关临床降低肠灌注状态并与血清降钙素原水平的上升相关联。 细菌内毒素在进行主动脉冠状动脉分流术中或结束后的人的血清中可检测得到。其也可在患有深度急性心肌炎的患者、经历数次手术患者、急性胰腺炎患者以及其他肠粘膜轻度充盈患者的血清中检出。这一猜测是因大肠菌转移到黏膜下层再与伴随物进入血液引起降钙素原水平的上升，如同一个激活原始免疫反应的市场。 了解科学可以增加信心。然而，血清降钙素原水平会影响患者关怀，也正因为这一点，临床医生需要降钙素原的结果。

32、作者强烈建议，如果可能，与白细胞计数相似，血清降钙素原水平将在任何时间段在实验室收集血清样本1小时内得到结果。速得的地降钙素原水平报告，可影响抗生素疗法决定的开始、持续或中断。在Albrich等人的研究中，美国参与医院的降钙素原规则遵循率仅35%。如果医生对他们在自身对因素的了解有更多的信心，遵循率还会增加，并推动血清降钙素原水平的上升或下降。 医学博士David Gilbert参考文献：1. Albrich WC, Dusemund F, Bucher B, et al. Effectiveness and safety of procalcitonin-guided antibiotic

33、therapy in lower respiratory tract infections in “real life”: an international, multicenter post-study survey (ProREAL). Arch Intern Med. 2012;172(9):715-722.2. Li H, Luo Y=F, Blackwell TS, Xie C-M. Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections.

34、Antimicrob Agent Chemother. 2011;55(12):5900-5906.3. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322-1331.4. Becker KL, Nylen ES, White JC, Muller B, Snider RHJr. Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab. 2004;89(4)15