A pre-post quasi-experimental study of antimicrobial stewardship exploring the impact of a multidisciplinary approach aimed at attaining an aggressive joint pharmacokinetic/pharmacodynamic target with ceftazidime/avibactam on treatment outcome of KPC-producing <i>Klebsiella pneumoniae</i> infections and on ceftazidime/avibactam resistance development
Milo Gatti, Matteo Rinaldi, Pier Giorgio Cojutti, Cecilia Bonazzetti, Antonio Daniele Pinna, Tommaso Tonetti, Simone Ambretti, Sara Tedeschi, Maddalena Giannella, Pierluigi Viale, Federico Pea
Abstract
ABSTRACT 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- Klebsiella pneumoniae (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%; P < 0.001), a lower clinical cure rate (48.3% vs. 70.6%; P < 0.001), and a higher rate of 90-day resistance development (15.5% vs. 5.9%; P = 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.