Cefepime in critically ill patients: continuous infusion versus intermittent regimen

Background

Beta-lactams have a time-dependent bactericidal activity and the time above MIC (T > MIC) is the best predictive factor of efficacy. The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters and the clinical efficacy of a continuous infusion of cefepime versus an intermittent regimen in critically ill adults patients with gram negative bacilli infection.

Methods

The prospective cross-over study was carried out in 34 patients with severe pneumonia (n = 26) or bacteriemia (n = 8). There were randomized to receive Cefepim 4 g per day either as a continuous infusion (Group 1, n = 17) or intermittent administration 2 g × 2 (Group 2, n = 17) in combination with amikacin 15 mg/kg/day in the two groups. Patients were significantly comparable in terms of age, sex, initial infection disease, IGS II score and MIC of gram negative bacilli isolated. Clinical outcomes: mechanical ventilation, ICU stay durations and clinical recovery were assessed along with pharmacokinetic (24-hour AUIC, 12-hour AUIC) and pharmacodynamic (T > MIC and T > 5 MICs) in both groups and compared (chi-squared and Mann–Whitney U-tests). Results with P < 0.05 were considered significant.

Results

Mechanical ventilation, clinical recovery (13 vs 11), bacteriologic eradication (12 vs 10) and duration of stay in ICU (35 vs 38 days) were better in Group 1 but did not significantly differ between the two group. Neither did 24-hour AUIC (569 vs 414) nor 12-hour AUIC (218 vs 202). However, T > MIC in Group 1 (23.8 ± 0.2) was significantly higher (P < 0.05) than in Group 2 (20.4 ± 3). T > 5 MICs in Group 1 (23.6 ± 0.6) was also very significantly higher (P < 0.01) than in Group 2 (16.7 ± 6).

Conclusion

Clinical outcome was similar but our results indicate that continuous infusion likely provides a better steady bactericidal effect with concentration above MIC than intermittent administration, especially if there is a high risk of cephalosporinase as with Enterobacter spp. Further studies including more patients are necessary to confirm the interest of continuous infusion and to assess the possibility of reducing the daily dosage.