Infectious Diseases Unit, Department of Medical and Clinical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Institute of Infectious Diseases, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.
Int J Antimicrob Agents. 2018 Feb;51(2):244-248. doi: 10.1016/j.ijantimicag.2017.08.019. Epub 2017 Aug 24.
To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI).
Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model.
595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20-1.43, P <0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19-4.50, P <0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02-2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25-0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43-0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L.
In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.
评估高剂量（HD）碳青霉烯类联合治疗对单一致病菌耐碳青霉烯类肺炎克雷伯菌（CR-KP）血流感染（BSI）患者临床结局的影响。
对六家意大利大型教学医院六年来收治的使用联合抗生素治疗方案的所有 CR-KP BSI 成年患者进行了回顾性分析。为了控制 HD 碳青霉烯类联合治疗对 14 天死亡率的混杂影响，进行了多变量 Cox 回归分析。由于患者之间存在不平衡，因此在模型中加入了接受 HD 碳青霉烯类的倾向评分。
共分析了 595 例 CR-KP BSI 患者，77%的分离株显示碳青霉烯类 MIC≥16mg/L，428 例（71.9%）接受了 HD 碳青霉烯类联合治疗。总体而言，127 例患者（21.3%）在 BSI 发病后 14 天内死亡。多变量分析显示，Charlson 合并症指数（HR 1.31，95%CI 1.20-1.43，P<0.001）、BSI 发病时感染性休克（HR 3.14，95%CI 2.19-4.50，P<0.001）和多粘菌素耐药株（HR 1.52，95%CI 1.02-2.24，P=0.03）与 14 天死亡率独立相关，而入住外科病房（HR 0.44，95%CI 0.25-0.78，P=0.005）和 HD 碳青霉烯类的使用（HR 0.69，95%CI 0.47-1.00，P=0.05）是保护性因素。当调整倾向评分后，HD 碳青霉烯类的使用显示出更大的保护作用（HR 0.64，95%CI 0.43-0.95，P=0.03）。对碳青霉烯类 MIC 进行分层后，在碳青霉烯类 MIC≥16mg/L 的菌株中也观察到了 HD 碳青霉烯类的获益。
在接受 CR-KP BSI 联合治疗的患者中，使用 HD 碳青霉烯类似乎与更好的结局相关，即使存在高水平的碳青霉烯类耐药性。
