Continuous infusion and outpatient parenteral antimicrobial therapy with ceftazidime-avibactam: evaluation of efficacy based on therapeutic drug monitoring

Based on recent PK/PD evidence, continuous infusion (CI) of beta-lactam administration is increasingly recommended for serious infections. Since 2016, the combination of ceftazidime and avibactam (CAZ/AVI) is administered per manufacturer prescription as an intermittent infusion of 2,5g every 8 hours thus CI has not yet been evaluated in clinical trials. 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 in agreement with EUCAST breakpoint. Patients were initially given CAZ/AVI as CI of 5g q12h. CAZ/AVI dosages were adjusted according to therapeutic drug monitoring (TDM) of ceftazidime with a therapeutic goal of 4-5xT> MIC in the plasma and/or at the site of infection. The latter was extrapolated from plasma concentrations and literature data CAZ/AVI was administered as CI in ten of thirty-three infectious episodes in twenty-seven patients treated with CAZ/ AVI in our hospital. These infections were mainly caused by Pseudomonas aeruginosa (54,5%). Bacteremia occurred in 30% of cases and septic shock was only present in one patient. CAZ/AVI was used as monotherapy in 60% of cases. Clinical cure or improvement was achieved in 70 % of cases and microbiological cure was achieved in 6/7 (86%) evaluable cases (Table 1). Thirty days after the CAZ/AVI treatment onset, two patients (20%) had died, with death possibly related to uncontrolled infection in one case. Three patients were discharged home with an outpatient parenteral antimicrobial therapy (OPAT). Based on repeated TDM (3,5 samples/patient), therapeutic goals were achieved in 100% of cases in plasma and 88% of cases at the site of infection (8/10 evaluable), CAZ/AVI looked stable for 12-hour infusions and no drug-related adverse events were noted. Although the sample size was limited, our case series shows promising clinical results for CI of CAZ/AVI, including for OPAT. Based on repeated TDM, therapeutic goals were achieved in 100% of cases in plasma. CAZ/AVI looked stable for 12-hour infusions and no drug-related adverse events were noted.