Gatti Milo, Rinaldi Matteo, Cojutti Pier Giorgio, Bonazzetti Cecilia, Siniscalchi Antonio, Tonetti Tommaso, Ambretti Simone, Tedeschi Sara, Giannella Maddalena, Viale Pierluigi, Pea Federico
Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Antimicrob Agents Chemother. 2025 Jul 2;69(7):e0048825. doi: 10.1128/aac.00488-25. Epub 2025 Jun 6.
To assess the impact of a multidisciplinary approach aimed at attaining aggressive joint pharmacokinetic/pharmacodynamic (PK/PD) target with ceftazidime/avibactam on treatment outcome of KPC- (Kp) infections and prevention of ceftazidime/avibactam resistance development, a pre-post quasi-experimental study on adult patients with documented KPC-Kp who were treated with ceftazidime/avibactam according to a multidisciplinary approach in the period 1 March 2021-31 October 2024 and patients receiving standard management with ceftazidime/avibactam in the period 1 January 2018-28 February 2021 was performed. Multivariate analysis was performed to identify variables associated with microbiological failure and 90-day resistance development to ceftazidime/avibactam in both pre- and post-intervention phases. A total of 116 and 102 patients in pre- and post-intervention phases were included. A significantly lower microbiological eradication rate (53.0% vs. 81.0%; < 0.001), a lower clinical cure rate (48.3% vs. 70.6%; < 0.001), and a higher rate of 90-day resistance development (15.5% vs. 5.9%; = 0.02) were found in the pre-intervention phase. Continuous renal replacement therapy (odds ratio [OR] 5.20; 95% confidence interval [CI] 1.21-22.34) and a ceftazidime/avibactam MIC value ≥ 4 mg/L (OR 3.08; 95% CI 1.10-8.64) emerged as independent predictors of microbiological failure in the pre-intervention phase. Conversely, attaining aggressive joint PK/PD target (OR 0.03; 95% CI 0.005-0.20) and bloodstream infections (OR 0.09; 95% CI 0.02-0.53) resulted in protection against microbiological failure in the post-intervention phase. Attaining aggressive joint PK/PD targets resulted in protection against 90-day resistance development in the post-intervention phase (OR 0.07; 95% CI 0.01-0.69). Implementing a multidisciplinary approach for maximizing the attainment of aggressive joint PK/PD targets of ceftazidime/avibactam could represent an effective strategy for preventing resistance development to ceftazidime/avibactam in KPC-Kp infections.
为评估旨在通过头孢他啶/阿维巴坦实现积极的联合药代动力学/药效学（PK/PD）目标的多学科方法对KPC-（Kp）感染治疗结果及预防头孢他啶/阿维巴坦耐药性产生的影响，我们对2021年3月1日至2024年10月31日期间按照多学科方法接受头孢他啶/阿维巴坦治疗的有记录的KPC-Kp成年患者，以及2018年1月1日至2021年2月28日期间接受头孢他啶/阿维巴坦标准治疗的患者进行了一项前后对照的准实验研究。进行多变量分析以确定干预前和干预后阶段与微生物学治疗失败及对头孢他啶/阿维巴坦90天耐药性产生相关的变量。干预前和干预后阶段分别纳入了116例和102例患者。干预前阶段发现微生物清除率显著更低（53.0%对81.0%；<0.001）、临床治愈率更低（48.3%对70.6%；<0.001）以及90天耐药性产生率更高（15.5%对5.9%；=0.02）。连续性肾脏替代治疗（优势比[OR]5.20；95%置信区间[CI]1.21 - 22.34）和头孢他啶/阿维巴坦最低抑菌浓度（MIC）值≥4 mg/L（OR 3.08；95% CI 1.10 - 8.64）成为干预前阶段微生物学治疗失败的独立预测因素。相反，实现积极的联合PK/PD目标（OR 0.03；95% CI 0.005 - 0.20）和血流感染（OR 0.09；95% CI 0.02 - 0.53）在干预后阶段可预防微生物学治疗失败。实现积极的联合PK/PD目标在干预后阶段可预防90天耐药性产生（OR 0.07；95% CI 0.01 - 0.69）。实施多学科方法以最大程度实现头孢他啶/阿维巴坦积极的联合PK/PD目标可能是预防KPC-Kp感染中对头孢他啶/阿维巴坦耐药性产生的有效策略。
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