Continuous infusion versus intermittent infusion of ceftazidime for the treatment of pneumonia caused by Pseudomonas aeruginosa

Objective

Beta-lactamics antibiotics exhibit concentration-independent bactericidal activity. Several studies have found that ceftazidime by continuous infusion appears to optimise the pharmacodynamic profile by constantly providing concentrations in excess of the minimum inhibitory concentration of susceptible organisms over the course of therapy. Limited data exist on clinical efficacy by continuous infusion of ceftazidime. The purpose of this study was to evaluate the clinical efficacy associated with the administration of continuous infusion of ceftazidime (CI) and intermittent infusion of ceftazidime (II) for the treatment of ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa.

Methods

An historic control group (1 July 2000–20 June 2002) with VAP caused by P. aeruginosa who received initial empiric antibiotic therapy with ceftazidime by II (n = 32) was compared with a prospective cohort of patients (1 July 2002–30 June 2003) treated with ceftazidime by CI (n = 15), at a university hospital medical–surgical ICU. Patients were treated during 14 days with ceftazidime, by CI (4 g/day) or II (2 g/8 hours), plus tobramycin. Exclusion criteria was creatinine clearance < 60 ml/mn. Antibiotic clinical effect was categorized as cure or failure. Differences between groups were tested by means of Student's t test and exact chi-square by permutation, using Statxact Software 5.0.

Results

Significant differences were not found between both groups of patients (eight with CI and 12 with II) in sex, age, APACHE II score, diagnosis and organ dysfunction severity assessed by the Sepsis-related Organ Failure Assessment score. The CI group showed greater clinical cure rate than the II group (8 of 8 [100%] versus 4 of 12 [33.33%], P = 0.004) and smaller atributable mortality to VAP (0 of 8 [0%] versus 6 of 12 [50%], P = 0.024). In addition, CI patients received one-third less daily dose than those treated by II.

Conclusions

These data suggest that ceftazidime administration by continuous infusion may have more clinical efficacy that intermittent infusion, in treatment of VAP caused by P. aeruginosa.