Ceftazidime administered by continuous perfusion can improve the prognosis of ventilator-associated pneumonia

Objective

Ceftazidime is used for the treatment of ventilator-associated pneumonia (VAP) due to its recognized antipseudomonal activity. Standard ceftazidime treatment is by intermittent perfusion (IP); however, continuous perfusion (CP) may be advantageous since its antibacterial activity depends on exposure time at concentrations above the minimum inhibitory concentration. However, evidence of its clinical efficacy in the treatment of VAP as compared with IP is limited and controversial. Thus, the aim of the present study was to determine whether ceftazidime by CP represents an optimization of the VAP standard treatment.

Methods

We compared a prospective cohort of patients (n = 13) that received 4 g/day intravenous (IV) ceftzadime by CP with a historic control group (n = 32) that received 2 g/8 hours IV ceftazidime by IP. VAP were treated during 14 days with two antibiotics: ceftazidime plus another (aminoglycoside or quinolone). VAP was defined according to the following criteria: a chest radiographic examination showing new or progressive infiltrate; new onset of purulent sputum; significant quantitative culture of pathogen from respiratory secretions (tracheal aspirate > 10⁶ cfu/ml, bronchoalveolar lavage > 10⁴ cfu/ml or protected bronchial brush catheter > 10³ cfu/ml). Differences between groups were tested by means of the Student's t test and exact chi-square test by permutation, using the Statxact Software 5.0. A significant diference was defined as P < 0.05.

Results

There were no significant differences in age, sex, diagnosis, APACHE II score, etiologic agents, bacteremia, organ dysfunction and antimicrobial therapy between groups. The CP group showed significantly lower clinical failure (CP, 0/13 vs IP, 15/32 [46.87%], P = 0.001) and significantly lower mortality attributable to VAP (CP, 0/13 [0%] vs IP, 8/32 [25%], P = 0.049). In addition, CP patients received one-third less daily dose than those treated intermittently.

Conclusions

We conclude that ceftazidime administered by continuous perfusion, for the treatment of ventilator-associated pneumonia, may significantly improve the clinical efficacy compared with intermittent administration and reduce the antibiotic dosage.