Continuous infusion versus intermittent administration of cefepime in patients with Gram-negative bacilli bacteraemia

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Abstract
The objective of this study was to compare the pharmacokinetics of cefepime administered by continuous infusion and intermittent injection regimens. A prospective, randomized, cross-over study of ten patients with Gram-negative bacilli bacteraemia was conducted. All patients were randomized to receive cefepime either as a 4-g continuous infusion over 24 h for 48 h or a 2-g bolus administered intermittently intravenously every 12 h for 48 h. After 48 h the patients received the alternative dose regimen. Cefepime pharmacokinetic studies were carried out during hours 36–48 after the start of both regimens. All of the pathogens isolated from the blood in 7 patients had a minimum inhibitory concentration (MIC) < 1 μg mL−1. In both regimens, the serum cefepime concentrations at all time points were higher than the MIC for the pathogens isolated from this study. For the continuous infusion arm, the highest steady-state concentration was 49.80±18.40 μg mL−1 and the lowest steady-state concentration was 41.42±16.48 μg mL−1. The steady-state concentrations were greater than 4 times the MIC of 8 μg mL−1. For the intermittent injection regimen, the mean trough concentration was 4.74±3.99 μg mL−1. The mean serum cefepime concentration was above 8 μg mL−1 for 81.66% of the dosing interval. Therefore, we conclude that either continuous infusion or intermittent injection can be used as an effective mode of cefepime administration to achieve bactericidal activity.