Continuous versus intermittent cefepime infusion in critical care patients. Preliminary findings.

The bactericidal activity of p-lactams is time-dependent, and the time spen t above the MIC (T > MIC) is the best predictor of efficacy. A prospective, randomized open-label study was conducted in intensive care unit (ICU) pat ients with gram-negative rod infections to compare the efficacy of cefepime given as a continuous versus an intermittent infusion. Of the 18 patients included to date, 14 had severe pneumonia and four bacteremia. All patients received amikacin, 15 mg/kg/d and cefepime, 4 g/d. Patients were randomize d to cefepime administration as a continuous infusion (Group 1, n = 9) or a s an intermittent infusion (Group 2, n = 9, 2 g every 12 h). No significant differences were found between the two groups for age, sex, initial infect ion, IGS II score (46 vs 48, NS) or the MIC of the gram-negative organism. Mechanical ventilation and hospital stay durations, recovery rates, and pha rmacokinetic parameters (24-h AUIC, 12-h AUIC, T > MIC, and T > 5 MIC) were compared in the two groups using the chi-square and Mann-Whitney tests. P values <0.05 were considered statistically significant. There were no signi ficant differences for mechanical ventilation duration, recovery rate, hosp ital stay duration (34 vs 36 days, NS), 24-h AUIC (624 vs 473, NS), or the 12-h AUIC (235 vs 238, NS). There were two interesting findings: T > MIC wa s significantly (P < 0.05) higher in Group 1 (23.84+/-0.2) than in Group 2 (20.7+/-3), and T >5 x MIC was also significantly (P < 0.01) higher in Grou p 1 (23.61+/-0.6) than in Group 2 (16.6+/-6). Although clinical outcomes we re similar in the two groups, it is reasonable to assume that the longer ti me spent with a cefepime level above the MIC in the continuous infusion gro up was associated with a more stable bactericidal effect.