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[NEJM读者来信]:降钙素原指导抗生素使用
2018年11月19日 研究点评, 进展交流 暂无评论

CORRESPONDENCE

Procalcitonin-Guided Antibiotic Use

N Engl J Med 2018; 379:1971-1973

DOI: 10.1056/NEJMc1811150

TO THE EDITOR

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.

Huang等人报告根据降钙素原水平指导抗生素处方的阴性结果与我们作为最早应用这一指标的急诊科的经验并不一致。2014年以来,我们已经对超过4000名患者进行了降钙素原快速检测。当无法确定支气管炎或肺炎诊断时,降钙素原对于病毒及细菌感染的鉴别能力就显得十分有帮助。由于上述两种情况均可因病毒感染引起,因此,降钙素原检测结果作为指导,能够显著减少急诊科抗生素的使用。遗憾的是,研究人群中接近半数符合这两种诊断。多数支气管炎患者依从降钙素原指导,急诊科抗生素使用减少14.8%。相反,对于肺炎患者,降钙素原检测结果几乎都被忽视(77.7%的患者降钙素原结果为阴性,但71.9%的患者使用抗生素)。简言之,即使多数患者肺炎严重程度指数(PSI)评分提示为低危(60%的患者PSI分级为I或II级肺炎),临床医生并不相信降钙素原结果,这可以解释急诊科用于治疗肺炎的抗生素仅仅减少4.4%的结果。今后的研究应当着眼于降钙素原检测用于疑似肺炎患者的价值。

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

 

TO THE EDITOR

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.

Huang等人评价了降钙素原指导对于下呼吸道感染诊疗的作用。已有建议将感染性疾病的快速分子诊断方法纳入诊断及抗生素管理措施,但在没有抗生素管理(ASP)的情况下可能无法导致临床获益。在干预组,尽管808名患者中的746名(92.3%)初始降钙素原水平提示无需使用抗生素,但仍有34.1%和57.0%的患者在急诊科及第30天内使用抗生素。这一结果提示,在降钙素原检测结果解读及停用抗生素的决策方面,ASP仍大有可为。尽管我们也赞同ProHOSP研究中观察到的方案依从性在真实世界中无法实现,但我们仍然相信,积极的ASP(包括前瞻性审核与反馈)具有可行性,我们采取这一策略也获得了成功。因此,研究结论不应当是降钙素原没有意义,而应当是在没有ASP的支持下使用降钙素原可能无法实现预期结果。

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

TO THE EDITOR

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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