Castón Juan José, Cano Angela, Pérez-Camacho Inés, Aguado Jose M, Carratalá Jordi, Ramasco Fernando, Soriano Alex, Pintado Vicente, Castelo-Corral Laura, Sousa Adrian, Fariñas María Carmen, Muñoz Patricia, Abril López De Medrano Vicente, Sanz-Peláez Óscar, Los-Arcos Ibai, Gracia-Ahufinger Irene, Pérez-Nadales Elena, Vidal Elisa, Doblas Antonio, Natera Clara, Martínez-Martínez Luis, Torre-Cisneros Julian
Infectious Diseases Unit, Hospital Universitario Reina Sofía, Cordoba, Spain.
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
J Antimicrob Chemother. 2022 Apr 27;77(5):1452-1460. doi: 10.1093/jac/dkac049.
Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown.
We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis.
The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02).
Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.
在头孢他啶/阿维巴坦的关键试验中，产碳青霉烯酶肠杆菌科细菌（CPE）引起的感染未得到充分体现。治疗这些感染的最佳策略尚不清楚。
我们对接受≥48小时头孢他啶/阿维巴坦或最佳可用治疗（BAT）以治疗确诊的CPE感染的患者进行了一项多中心回顾性观察研究。主要结局是30天粗死亡率。次要结局是21天临床反应和微生物学反应。使用多变量逻辑回归模型确定预测30天粗死亡率的因素。在分析中，将接受头孢他啶/阿维巴坦治疗的倾向评分用作协变量。
该队列包括339例CPE感染患者。189例（55.8%）患者使用了头孢他啶/阿维巴坦治疗，150例（44.2%）患者在感染诊断后中位数2天接受了BAT治疗。在多变量分析中，头孢他啶/阿维巴坦治疗与生存相关（比值比0.41，95%置信区间0.20 - 0.80；P = 0.01），而INCREMENT - CPE评分>7分（比值比2.57，95%置信区间1.18 - 1.5.58；P = 0.01）和序贯器官衰竭评估（SOFA）评分（比值比1.20，95%置信区间1.08 - 1.34；P = 0.001）与较高死亡率相关。在INCREMENT - CPE评分>7分的患者中，与BAT相比，头孢他啶/阿维巴坦治疗与较低死亡率相关（16/73，21.9%对23/49，46.9%；P = 0.004）。头孢他啶/阿维巴坦也是21天临床反应（比值比2.43，95%置信区间1.16 - 5.12；P = 0.02）和微生物清除（比值比0.40，95%置信区间0.18 - 0.85；P = 0.02）的独立因素。
头孢他啶/阿维巴坦是治疗CPE感染的有效替代方案,尤其是在INCREMENT - CPE评分>7分的患者中。一项随机对照试验应证实这些发现。
