Article Text

Download PDFPDF

4CPS-031 Therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion: PK/PD target achievement and clinical outcomes
  1. D Fresan1,
  2. S Luque2,
  3. J Miedes2,
  4. C Bosch2,
  5. A Benítez-Cano3,
  6. L Sorlí4,
  7. M De-Antonio2,
  8. N Prim5,
  9. V Vega6,
  10. JP Horcajada4,
  11. S Grau2
  1. 1Hospital Universitario de Navarra, Pharmacy Service, Pamplona, Spain
  2. 2Hospital Del Mar, Pharmacy, Barcelona, Spain
  3. 3Hospital Del Mar, Anaesthesiology and Surgical Intensive Care, Barcelona, Spain
  4. 4Hospital Del Mar, Infectious Diseases, Barcelona, Spain
  5. 5Laboratori de Referència de Catalunya, Microbiology Department, Barcelona, Spain
  6. 6Laboratori de Referència de Catalunya, Analytical Department, Barcelona, Spain


Background and Importance Ceftazidime/avibactam (CAZ/AVI) is a novel betalactam antibiotic utilised for multi-drug resistant (MDR) gram-negative bacteria. Therapeutic drug monitoring (TDM) ensures that CAZ/AVI levels achieve the pharmacokinetic/pharmacodynamic (PK/PD) target. Continuous infusion (CI) has been used to optimise CAZ/AVI pharmacodynamics.

Aim and Objectives To analyse the correlation between PK/PD target attainment of CAZ/AVI administered by CI, clinical outcomes and toxicity.

Material and Methods Patients treated with CAZ/AVI administered by CI and undergoing TDM of the CAZ plasma concentrations were included. Definitions:

CAZ/AVI PK/PD target:

  • time that CAZ free concentrations remain 4 times above the minimum inhibitory concentration (MIC) of the causative pathogen (%fT>4xMIC).

  • Overexposure:%fT>10xMIC.

  • Clinical cure: disappearance of all signs and symptoms related to the infection and no requirement for additional antibiotic treatment initiation (except as part of de-escalation strategy) for the disease to be investigated within 48h after completion of the study drug.

  • Thirty-day all-cause mortality: death from any cause during the 30 days following the end of treatment.

When real MIC was not available, a MIC of 8 mg/L was assumed.

Results Thirty-one patients (28 males, median (range) age of 64 (37-78) years) infected with extensively drug-resistant Pseudomonas aeruginosa and extended-spectrum betalactamase-producing Klebsiella pneumoniae were included (26 directed treatments and 5 empirical).

Twenty-six (83.9%) achieved the PK/PD target, 15 of which presented overexposure. Only 4 (26.6%) overexposed patients presented adverse reactions (3 increased liver enzymes and 1 thrombocytopenia).

Twenty-one (67.7%) patients achieved clinical cure, 18 (85.7%) of which achieved the PK/PD target. There was a higher frequency of patients with a%fT>4xMIC that achieved clinical cure (18/26 (69.2%) in patients with clinical cure vs 2/5 (40%) with clinical failure, p= 0.686).

The 30-day all-cause mortality was 19.4% (6 patients). A lower mortality rate was observed in patients that did achieve a%fT>4xMIC (14.8%) in patients who survived vs 50% in those who died, p=0.096.

Conclusion and Relevance CI seems a useful strategy to reach the PK/PD target of CAZ/AVI. Few patients with overexposure presented adverse events. There seems to be a correlation between PK/PD target attainment, clinical cure and 30-day all-cause mortality but larger studies with bigger samples are needed.

Conflict of Interest No conflict of interest

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.