瑞士日内瓦大学医院Angela Huttner团队探讨了C反应蛋白指导的抗生素用药时间、连续7天或14天治疗单纯革兰氏阴性菌血症患者的疗效。该成果于2020年6月2日发表在《美国医学会杂志》上。

抗生素过度使用会导致抗生素耐药性。革兰阴性菌血症感染常使用大量抗生素。

为了比较C反应蛋白（CRP）指导抗生素用药时间、连续治疗7天、14天，在初始治疗30天、60天和90天后的临床效果，2017年4月至2019年5月，研究组在瑞士3所三级医院进行了一项多中心、非劣效、即时检验的随机临床试验，招募革兰氏阴性菌血症住院的成人，并随访至2019年8月。若成人患者在没有复杂感染（如脓肿）或严重免疫抑制迹象的情况下发烧24小时，则可进行革兰氏阴性菌血液培养。

最终共招募了504名符合条件的患者，以1：1：1的比例进行随机分组，其中170例接受以个性化CRP指导的抗生素治疗，一旦CRP从峰值下降75％则停药；169例接受抗生素连续治疗7天；165例接受抗生素连续治疗14天。主要结局是第30天的临床失败率。其中临床失败定义为复发性菌血症、局部化脓性并发症、远处并发症、因临床恶化而重新开始革兰阴性导向抗生素治疗、或全因死亡。

504例患者的中位年龄为79岁，61％为女性，493例（98％）完成了30天的随访，448例（89％）完成了90天的随访。CRP组抗生素治疗的中位持续时间为7天，在完成30天随访的164例患者中，有34例（21％）违反了治疗分组相关规定。CRP组中有2.4％的患者第30天发生临床失败，7天组为6.6％，14天组为5.5%，其中CRP组和14天组均显著低于7天组。第90天时，CRP组中有7.0%的患者发生临床失败，7天组为10.6%，14天组为10.5%。

总之，对于非复杂的革兰氏阴性菌血症的成年人，CRP指导的抗生素治疗持续时间和连续7天治疗，其30天临床失败率不逊于连续14天治疗。

附：英文原文

Title: Effect of C-Reactive Protein–Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial

Author: Elodie von Dach, Werner C. Albrich, Anne-Sophie Brunel, Virginie Prendki, Clémence Cuvelier, Domenica Flury, Angèle Gayet-Ageron, Benedikt Huttner, Philipp Kohler, Eva Lemmenmeier, Shawna McCallin, Anne Rossel, Stephan Harbarth, Laurent Kaiser, Pierre-Yves Bochud, Angela Huttner

Issue&Volume: 2020/06/02

Abstract: Importance  Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use.

Objective  To compare the clinical effectiveness of C-reactive protein (CRP)–guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation.

Design, Setting, and Participants  Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019. Patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged ≥18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression.

Intervention  Randomization in a 1:1:1 ratio to an individualized CRP-guided antibiotic treatment duration (discontinuation once CRP declined by 75% from peak; n=170), fixed 7-day treatment duration (n=169), or fixed 14-day treatment duration (n=165).

Main Outcomes and Measures  The primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative–directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up.

Results  Among 504 patients randomized (median [interquartile range] age, 79 [68-86] years; 306 of 503 [61%] were women), 493 (98%) completed 30-day follow-up and 448 (89%) completed 90-day follow-up. Median antibiotic duration in the CRP group was 7 (interquartile range, 6-10; range, 5-28) days; 34 of the 164 patients (21%) who completed the 30-day follow-up had protocol violations related to treatment assignment. The primary outcome occurred in 4 of 164 (2.4%) patients in the CRP group, 11 of 166 (6.6%) in the 7-day group, and 9 of 163 (5.5%) in the 14-day group (difference in CRP vs 14-day group, 3.1% [1-sided 97.5% CI, ∞ to 1.1]; P<.001; difference in 7-day vs 14-day group, 1.1% [1-sided 97.5% CI, ∞ to 6.3]; P<.001). By day 90, clinical failure occurred in 10 of 143 patients (7.0%) in the CRP group, 16 of 151 (10.6%) in the 7-day group, and 16 of 153 (10.5%) in the 14-day group.

Conclusions and Relevance  Among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with the low observed event rate, as well as low adherence and wide range of treatment durations in the CRP-guided group.

DOI: 10.1001/jama.2020.6348

Source: https://jamanetwork.com/journals/jama/article-abstract/2766635