A multifaceted strategy to optimize pharmacokinetics of antimicrobial therapy in patients with hospital-acquired infections-a monocentre quality improvement project

Objective: We assessed the efficacy of a quality improvement programme to optimize the delivery of antimicrobial therapy in critically ill patients with hospital-acquired infections (HAI). Patients and methods: Before-after trial in a university hospital in France. Consecutive adults receiving systemic antimicrobial therapy for HAI were included. Patients received standard care during the pre-intervention period (June 2017 to November 2017). The quality improvement programme was implemented in December 2017. During the intervention period (January 2018 to June 2019), clinicians were trained to dose adjustment based on therapeutic drug monitoring and continuous infusion of beta-lactam antibiotics. The primary endpoint was the mortality rate at day 90. Results: A total of 198 patients were included (58 pre-intervention, 140 intervention). The compliance with the therapeutic drug monitoring-dose adaptation increased from 20.3% to 59.3% after the intervention (P < 0.0001). The 90-day mortality rate was 27.6% in the pre-intervention period and 17.3% in the intervention group (adjusted relative risk 0.53, 95%CI 0.27-1.07, P = 0.08). Treatment failures were observed in 22 (37.9%) patients before and 36 (25.7%) patients after the intervention (P = 0.07). Conclusions: Recommendations for therapeutic drug monitoring-dose adaptation and continuous infusion of beta-lactam antibiotics were not associated with a reduction in the 90-day mortality rate in patients with HAI.