Background: Beta-lactam antibiotics are reported to exhibit time-dependent bactericidal activity. However, there are limited data on the clinical efficacy of ceftazidime administered by continuous infusion.
Objective: The objective of this study was to compare the clinical efficacy of ceftazidime administered by continuous infusion and by intermittent infusion in the treatment of ventilator-associated pneumonia (VAP) caused by gram-negative bacteria.
Methods: This was a retrospective chart review of patients with VAP caused by gram-negative bacteria who were treated with initial empiric ceftazidime therapy in the intensive care unit (ICU) over a 5-year period (from June 2002 to June 2007). The intermittent-infusion group received ceftazidime 2 g infused over 30 minutes every 12 hours; the continuous-infusion group received a ceftazidime loading dose of 1 g over 30 minutes, followed by 2 g infused over 720 minutes every 12 hours. Data extracted from patients' charts included sex, age, severity of the patient's condition at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II] score), diagnosis group, weight, creatinine clearance, MIC of the organism responsible for VAP, and severity of organ dysfunction at the time VAP was suspected (Sepsis-related Organ Failure Assessment [SOFA] score). Each clinical history was reviewed by a group of 6 staff intensivists who were blinded to whether the patient received ceftazidime by continuous or intermittent infusion. The clinical effect of treatment was categorized as cure (complete resolution of all clinical signs and symptoms of pneumonia) or failure (persistence or progression of any sign or symptom of pneumonia).
Results: The final sample consisted of 121 patients, of whom 88 (72.7%) were males. The mean (SD) age of the population was 62.87 (9.35) years. The mean APACHE II score on admission to the ICU was 16.08 (2.17), the SOFA score at suspicion of VAP was 8.80 (2.06), and the MIC of the organism responsible for VAP was 2.77 (2.24) microg/mL. There were no significant differences in these and other characteristics at baseline between those who received ceftazidime by continuous infusion (n = 56) and those who received ceftazidime by intermittent infusion (n = 65). On logistic regression analysis, continuous infusion was associated with a greater clinical cure rate than intermittent infusion (50/56 [89.3%] vs 34/65 [52.3%], respectively; odds ratio [OR] = 12.2; 95% CI, 3.47-43.21; P < 0.001). Patients with VAP caused by organisms with an MIC of 8 microg/mL had lower cure rates compared with those with VAP caused by organisms with an MIC < or =2 microg/mL (OR = 0.2; 95% CI, 0.04-0.71; P = 0.02) but not compared with those with an MIC of 4 microg/mL. No significant interaction was found between the type of ceftazidime infusion and the MIC of the causative organism.
Conclusion: In this small, selected population of adult patients with VAP caused by gram-negative bacteria who were treated in a nonrandomized, open-label manner, ceftazidime administered by continuous infusion had greater clinical efficacy than ceftazidime administered by intermittent infusion.