Mazzitelli Maria, Gregori Dario, Sasset Lolita, Trevenzoli Marco, Scaglione Vincenzo, Lo Menzo Sara, Marinello Serena, Mengato Daniele, Venturini Francesca, Tiberio Ivo, Navalesi Paolo, Cattelan Annamaria
Infectious and Tropical Diseases Unit, Padua University Hospital, 35128 Padua, Italy.
Unit of Biostatistics, Epidemiology and Public Health, DCTVPH, University of Padova, 35128 Padua, Italy.
Microorganisms. 2023 Apr 10;11(4):984. doi: 10.3390/microorganisms11040984.
A large increase in multi-drug-resistant , especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant (CR-Ab), but to date, the guidelines and evidence available are conflicting.
We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted.
We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR).
Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.
在新冠疫情的头两年，多重耐药菌尤其是耐碳青霉烯类菌株大幅增加，给其治疗带来了重大挑战。头孢地尔似乎是治疗耐碳青霉烯类鲍曼不动杆菌（CR-Ab）的一个不错选择，但迄今为止，现有的指南和证据相互矛盾。
我们回顾性纳入了帕多瓦大学医院（2020年8月至2022年7月）一组感染CR-Ab的患者（接受以黏菌素或头孢地尔为基础的治疗方案），评估30天死亡率的预测因素以及微生物学和临床治疗的差异。为了评估结果的差异，考虑到抗生素治疗分配的不平衡，采用了倾向评分加权（PSW）方法。
我们纳入了111例患者，68%为男性，中位年龄69岁（四分位间距：59 - 78岁）。抗生素治疗的中位持续时间为13天（四分位间距：11 - 16天）。总共有60例（54.1%）和51例（45.9%）患者分别接受了以头孢地尔和黏菌素为基础的治疗。值得注意的是，53例（47.7%）患者发生血流感染，而58例（52.3%）患者发生肺炎。黏菌素分别与替加环素、美罗培南和磷霉素联合使用的病例比例为96.1%、80.4%和5.8%。头孢地尔分别与磷霉素、替加环素和美罗培南联合使用的病例比例为13.3%、30%和18.3%。在基线时，两个治疗组在年龄（接受黏菌素治疗的患者年龄显著更大）、糖尿病和肥胖的患病率（在接受黏菌素治疗的组中更常见）、住院时间（接受头孢地尔治疗的组更长）以及感染类型（血流感染在接受头孢地尔治疗的组中更常见）方面存在显著差异。黏菌素组发生急性肾损伤的患者比例显著更高。通过使用PSW，两组在死亡率或临床及微生物学治愈方面未出现统计学上的显著差异。未检测到医院死亡率或临床治愈的独立预测因素，而对于住院时间，唯一选定的预测因素是年龄，随着年龄增长（在四分位间距范围内计算），对住院时间延长的非线性效应（非线性P值为0.025）为0.25天（95%置信区间0.10 - 0.39）。
头孢地尔治疗在主要结局和安全性方面与基于黏菌素的治疗方案没有差异。需要更多纳入大量患者的前瞻性研究来证实我们的结果。
