Value of pharmacokinetic/pharmacodynamic in dose management of ceftazidime and imipeneme in ICUs

Abstract number: P1257

Coudrot M., Carricajo A., Guyomarc'h S., Morel J., Auboyer C., Zeni F., Aubert G.

Objectives: the purpose of our study was to assess the value of serum assay of ceftazidime (CAZ) and imipeneme (IMI) in patients in the intensive care unit (ICU) of the Saint-Etienne University Teaching Hospital and in other ICUs in the region with regard to optimisation of treatment management.

Methods: Between 01/11/05 and 31/10/07, in patients hospitalised in ICUs, not on dialysis and undergoing treatment with CAZ given in a continuous infusion or with IMI (non-continuous), serum assay of the respective antibiotics was performed 36 hours after the start treatment using a single serum sample for CAZ and determination of trough and peak concentrations for IMI. Assays were performed using the microbiology technique with results 18 hours after sample collection. CAZ 2 g was given systematically in a bolus at the start of treatment.

Results: assay was performed in 81 and 95 patients respectively for CAZ and IMI. Mean patient age was 66 years (19 to 89 years) and mean weight was 73 kg (33 to 122 kg). The dosage was between 1 g and 6 g/24 h for CAZ and between 500 mg and 6 g/24 h for IMI. The mean serum CAZ concentration was 47.6 mg/L (7.4 to 162.3 mg/L). Serum CAZ concentrations were as follows: 35 to 65 mg/L in 37% of patients, <35 mg/L in 43.2% and >65 mg/L in 19.8%. Infection was established in 61 patients, with 52 strains of P. aeruginosa detected. The serum concentration/MIC ratio was 5 for 84.4% of patients and >10 for 65.6% of patients. Trough concentrations of IMI were <0.5 mg/L for 14.7% of patients, between 0.5 and 2 mg/L for 43.2%, and >2 mg/L for 42.1%. The mean peak concentration of IMI was 19.9 mg/L (3 to 78 mg/L). Infection was recorded in 52 patients, including 22 Enterobacter spp. and 12 P. aeruginosa. Antibiotic dosage was adjusted respectively for CAZ and IMI in 19.8% and 28.4% of patients based on the initial assay results.

Conclusion: Our study shows that assays are needed in ICUs to confirm the efficacy of time-dependent antibiotics, to avoid treatment toxicity, to achieve efficacy as rapidly as possible and to avoid selection of resistant mutants, particularly in strains having limited susceptibility to antibiotics.