Continuous Infusion, Therapeutic Drug Monitoring and Outpatient Parenteral Antimicrobial Therapy with Ceftazidime-Avibactam: a Retrospective Cohort Study.

ABSTRACT Background Based on recent PK/PD evidence, continuous infusion (CI) of β-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 q8h. 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 5g q12h and dosages were adjusted according to therapeutic drug monitoring of ceftazidime with a therapeutic goal ≥ 4-5 X MIC in plasma and/or at the site of infection. Results CAZ/AVI was administered through CI in 10 patients whose infections were mainly caused by MDR Pseudomonas aeruginosa (54.5%) and Klebsiella pneumoniae (36.4%). Bacteremia 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. 30-day mortality after CAZ/AVI treatment onset was 10%. The therapeutic goals ≥ 4-5 X MIC in plasma and/or at the site of infection were achieved in 100% and 87.5% of cases, respectively, without adverse events. Conclusions Despite a limited number of patients, CAZ/AVI in CI provided promising results after optimization of PK/PD parameters both in plasma and at the site of infection.