Infectious Diseases Unit, Raymond-Poincaré University Hospital, Assistance Publique-Hôpitaux de Paris (APHP) Paris Saclay University, Garches, France.
Epidemiology and Modeling of Bacterial Evasion to Antibacterials Unit, Institut Pasteur, Paris, France.
JAMA Netw Open. 2021 Oct 1;4(10):e2129566. doi: 10.1001/jamanetworkopen.2021.29566.
Failure of treatment is the most serious complication in community-acquired pneumonia (CAP).
To assess the potential risk factors for treatment failure in clinically stable patients with CAP.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population.
Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive β-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days.
The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of β-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions.
Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis.
In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.
治疗失败是社区获得性肺炎（CAP）最严重的并发症。
评估 CAP 临床稳定患者治疗失败的潜在危险因素。
设计、地点和参与者：这项二次分析评估了 2013 年 12 月 19 日至 2018 年 2 月 1 日进行的 CAP 随机临床试验（肺炎短期治疗[PTC]试验）的数据。数据分析于 2019 年 7 月 18 日至 2020 年 2 月 15 日进行。在法国的 16 个中心之一住院的中度严重 CAP 患者，在抗生素治疗第 3 天临床稳定时，符合 PTC 试验纳入标准并在符合方案人群中进行分析。
在抗生素治疗第 3 天，患者被随机（1:1）分为接受β-内酰胺（阿莫西林-克拉维酸[1g/125mg]，每日 3 次）或安慰剂治疗 5 天。
主要结局是首次抗生素摄入后 15 天的治疗失败，定义为体温大于 37.9°C 和/或呼吸道症状无缓解或改善和/或因任何原因再次使用抗生素治疗。通过单变量和多变量逻辑回归评估符合方案试验人群中人口统计学特征、基线临床和生物学变量（即在开始使用β-内酰胺治疗的第 1 天）与 15 天治疗失败之间的关系。
共有 310 名患者纳入研究，其中 291 名患者（174 名[59.8%]男性；平均[标准差]年龄 69.6[18.5]岁）进行了二次分析。失败率为 26.8%。男性（比值比[OR]，1.74；95%可信区间[CI]，1.01-3.07）、年龄每增加 1 岁（OR，1.03；95%CI，1.01-1.05）、肺炎严重指数评分（OR，1.01；95%CI，1.00-1.02）、慢性肺部疾病（OR，1.85；95%CI，1.03-3.30）和肌酐清除率（OR，0.99；95%CI，0.98-1.00）与单变量分析中的失败显著相关。当在回归模型中排除肺炎严重指数评分以避免与年龄和性别之间的共线性时，仅男性（OR，1.92；95%CI，1.08-3.49）和年龄（OR，1.02；95%CI，1.00-1.05）与治疗失败相关。
在这项随机临床试验的二次分析中，在 CAP 患者接受 3 天抗生素治疗后达到临床稳定的患者中，只有男性和年龄与治疗失败的风险增加有关，与抗生素治疗持续时间和生物标志物水平无关。需要进行另一项随机临床试验来评估在治疗失败风险较高的人群中治疗持续时间的影响。
