Dalfino Lidia, Stufano Monica, Bavaro Davide Fiore, Diella Lucia, Belati Alessandra, Stolfa Stefania, Romanelli Federica, Ronga Luigi, Di Mussi Rosa, Murgolo Francesco, Loconsole Daniela, Chironna Maria, Mosca Adriana, Montagna Maria Teresa, Saracino Annalisa, Grasso Salvatore
Intensive Care Unit II, Department of Precision Medicine, Ionic Area, University of Bari "A. Moro", 70124 Bari, Italy.
Clinic of Infectious Diseases, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro", 70124 Bari, Italy.
Antibiotics (Basel). 2023 Jun 14;12(6):1048. doi: 10.3390/antibiotics12061048.
Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.
对于由耐碳青霉烯类鲍曼不动杆菌（CRAB）引起的呼吸机相关性肺炎（VAP），基于循证的标准抗生素治疗是重症监护病房（ICU）中尚未满足的一项重要临床需求。我们旨在评估使用旧的和新型的对CRAB有效的抗生素进行一线治疗对CRAB引起的单微生物VAP的有效性。在一个非新冠混合ICU中进行了一项前瞻性观察性研究。主要结局指标是一线靶向治疗后的临床失败情况。还通过Cox比例多变量分析研究了独立影响失败发生的特征。为了应对抗生素治疗分配的不平衡，采用了倾向评分分析和逆概率治疗加权方法。在90名入组患者中，34名（38%）出现临床失败。与VAP临床缓解的患者相比，临床失败的患者年龄更大（中位年龄71岁（四分位间距64 - 78岁）对62岁（四分位间距52 - 69岁）），合并症负担更重（中位查尔森合并症指数8（四分位间距6 - 8）对4（四分位间距2 - 6）），免疫抑制频率更高（44%对21%），且VAP发病时临床严重程度更高（中位序贯器官衰竭评估（SOFA）评分10（四分位间距9 - 11）对9（四分位间距7 - 11））。一线治疗失败的患者中，医院获得性肺炎快速分子诊断的使用率较低（8.8%对30.3%），及时给予对CRAB有效的治疗的比例较低（65%对89%），基于多粘菌素的靶向治疗比例较高（71%对46%）。总体而言，50例患者的基于CRAB有效的静脉用药方案以多粘菌素为基础，40例患者以头孢地尔为基础，两者均始终联合吸入多粘菌素。根据一线方案的主要药物，头孢地尔组的临床失败率低于多粘菌素组（分别为25%对48%）。在多变量Cox回归分析中，合并症负担独立预测临床失败的发生（查尔森指数校正风险比（aHR）= 1.21，95%置信区间（CI）= 1.04 - 1.42，P = 0.01），而及时的靶向抗生素治疗（aHR = 0.40，95% CI = 0.19 - 0.84，P = 0.01）和基于头孢地尔的一线方案（aHR = 0.38，95% CI = 0.17 - 0.85，P = 0.02）可显著降低失败风险。在由CRAB引起的VAP患者中，及时的有效治疗可改善感染结局，头孢地尔有望作为一线治疗选择。
