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2018年11月19日 研究点评, 进展交流 暂无评论


Procalcitonin-Guided Antibiotic Use

N Engl J Med 2018; 379:1971-1973

DOI: 10.1056/NEJMc1811150


The null result for the use of procalcitonin level to guide the prescription of antibiotics, reported by Huang et al. (July 19 issue),1 is incongruent with our experience as an early emergency department (ED) adopter. Rapid procalcitonin assays have been ordered for more than 4000 patients since 2014. The ability of procalcitonin to differentiate viral from bacterial infections is most helpful when there is uncertainty as to whether a diagnosis of bronchitis or pneumonia should be made.2-4 Since both conditions often have viral causes, the results of a procalcitonin assay, if used as a guide, have the potential to substantially reduce ED antibiotic prescribing.5 Unfortunately, less than half of the trial participants had these diagnoses. For bronchitis, procalcitonin guidance was followed in most cases, yielding a 14.8% reduction in ED antibiotic prescribing.1 Conversely, in patients with pneumonia, the procalcitonin result was almost universally disregarded (77.7% of patients had a negative result on the procalcitonin assay, yet 71.9% received antibiotics).1 Simply put, clinicians did not trust procalcitonin even among a cohort of patients in which the majority had a Pneumonia Severity Index (PSI) score indicating low risk (with 60% having PSI Class I or II pneumonia), a factor that attenuated the observed 4.4% reduction in ED antibiotic prescribing for pneumonia.1Future work should focus on the usefulness and implementation of the procalcitonin assay for patients in whom pneumonia is suspected.


Michael S. Pulia, M.D.
Lucas T. Schulz, Pharm.D.
Barry C. Fox, M.D.
University of Wisconsin–Madison, Madison, WI



Huang et al. evaluated the implementation of procalcitonin guidance for the management of lower respiratory tract infections. Implementation of rapid molecular diagnostics for infectious disease is suggested to incorporate both diagnostic and antimicrobial stewardship,1 but implementation in the absence of an antimicrobial stewardship program (ASP) may fail to provide a clinical benefit.2 In the intervention group, even though 746 of 808 patients (92.3%) had an initial procalcitonin level that suggested antibiotics were not necessary, 34.1% and 57.0% of patients received antibiotics in the ED and by day 30, respectively. This observation suggests an opportunity for an ASP to provide real-time feedback on the interpretation of procalcitonin assays and the decision to discontinue antibiotics. Although we agree that the adherence to protocol exercised in trials such as ProHOSP (Procalcitonin Guided Antibiotic Therapy and Hospitalisation in Patients with Lower Respiratory Tract Infections)3 is not feasible in the real world, active ASP involvement, including the use of prospective audit and feedback, is possible, and we have had success with this strategy.4 Thus, the conclusion drawn should not be that procalcitonin is not useful but rather that its introduction in the absence of adequate ASP support may lead it to fall short of the desired outcome.


Derek N. Bremmer, Pharm.D.
Nathan R. Shively, M.D.
Thomas L. Walsh, M.D.
Allegheny General Hospital, Pittsburgh, PA


The failure of procalcitonin to decrease antibiotic use in the trial conducted by Huang et al. contradicts the findings from a meta-analysis of 26 randomized, controlled trials in which procalcitonin was reported to reduce antibiotic prescriptions, adverse events, and even mortality.1 According to the meta-analysis, antibiotics were administered to 86% of patients for a median of 8 days in control groups and to 72% of patients for a median of 6 days in procalcitonin groups.1 In contrast, in the trial conducted by Huang et al., an unusually low percentage of controls (<62%), and just one third of these patients in the ED, were treated with antibiotics for an average of only 4 days. In comparison, less than 10% of hospitals in California had antibiotic prescribing rates of less than 62% for patients with acute bronchitis in the state’s ongoing Medicaid pay-for-performance program. Thus, it may not be possible to extrapolate the new results to most settings, in which antibiotics are prescribed more intensively at baseline and in which procalcitonin may have better performance. Furthermore, in the trial conducted by Huang et al., more than 90% of the procalcitonin values were within ranges that “discouraged” or “strongly discouraged” antibiotic use, yet the majority of patients still received antibiotics, suggesting that stewardship support and training regarding the use of procalcitonin were inadequate.

在Huang等人的研究中,降钙素原无法减少减少抗生素使用,这一结果与26项随机对照试验的meta分析结果相反。meta分析发现,降钙素原能够减少抗生素使用,避免抗生素不良事件,甚至改善病死率。meta分析显示,对照组86%的患者使用抗生素,中位疗程8天,降钙素原组72%的患者使用抗生素,中位疗程6天。与此相反,在Huang等人的研究中,对照组患者接受抗生素治疗的比例异常低(< 62%),在急诊科就诊时仅1/3使用抗生素,中位疗程仅为4天。相比之下,不足10%的加州医院对急性支气管炎患者的抗生素处方率低于62%。因此,我们无法将研究结果推广到多数情况,即基线情况下抗生素使用更为普遍,此时降钙素原的作用更为明显。而且,Huang等人的研究中,尽管超过90%的降钙素原结果提示“不鼓励”或“强烈不鼓励”,但多数患者仍在使用抗生素,提示抗生素管理及有关降钙素原的培训不足。

Brad Spellberg, M.D.
Los Angeles County and University of Southern California Medical Center, Los Angeles, CA

Neil Gaffin, M.D.
Ridgewood Infectious Diseases Associates, Ridgewood, NJ


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