Continuous infusion, therapeutic drug monitoring and outpatient parenteral antimicrobial therapy with ceftazidime/avibactam: a retrospective cohort study

Abstract

Objectives: Based on recent pharmacokinetic/pharmacodynamic (PK/PD) evidence, continuous-infusion (CI) β-lactam administration is increasingly recommended for serious infections. Since 2016, the combination ceftazidime/avibactam (CAZ/AVI) is administered as per the manufacturer's instructions as an intermittent infusion of 2.5 g every 8 h. Thus, CI has not yet been evaluated in clinical trials.

Methods: We aimed to evaluate the use of CI of CAZ/AVI in a retrospective case series from December 2016 to October 2019. All isolates displayed in vitro susceptibility to CAZ/AVI according to EUCAST definitions. Patients were initially given CAZ/AVI as CI of 5 g every 12 h, and dosages were adjusted according to therapeutic drug monitoring of ceftazidime with a therapeutic goal of ≥4-5 × MIC in plasma and/or at the site of infection.

Results: CAZ/AVI was administered by CI in 10 patients with infections mainly caused by multidrug-resistant Pseudomonas aeruginosa (54.5%) and Klebsiella pneumoniae (36.4%). Bacteraemia occurred in 30% of cases. Sepsis or septic shock was present in 20% of cases. CAZ/AVI was used as monotherapy in 60% of cases. Clinical cure and microbiological eradication were achieved in 80% and 90% of cases, respectively. The 30-day mortality after CAZ/AVI treatment onset was 10%. The therapeutic goals of ≥4-5 × MIC in plasma and/or at the site of infection were achieved in 100% and 87.5% of cases, respectively, without adverse events.

Conclusion: Despite a limited number of patients, CI of CAZ/AVI provided promising results after optimisation of PK/PD parameters both in plasma and at the site of infection.

Keywords: Ceftazidime/avibactam; Continuous infusion; Multidrug-resistant infection; Outpatient parenteral antimicrobial therapy; Therapeutic drug monitoring.