Prospective determination of plasma imipenem concentrations in critically ill children

Abstract

Plasma imipenem concentrations were measured in 19 critically ill children (median age, 0.8 year; range, 0.02 to 12.9 years). Wide interindividual variations (2 to 4x at peak and >10x at trough concentrations) resulted in unpredictable plasma levels in several children. To avoid subtherapeutic drug levels, we recommend treatment with at least 100 mg/kg of body weight/day of imipenem-cilastatin for critically ill children requiring such therapy.

FIG. 1.

Imipenem concentrations in the plasmas of 19 critically children. All children received the same nominal dose of 100 mg/kg/day, given in either three separate infusions (q8h, open triangles) or four separate infusions (q6h, closed circles). The drug (50-mg vials) was dissolved in 100 ml of 0.9% NaCl, according to the manufacturer's recommendations, and infused over a period of 30 min via an infusion pump (BD Pilote C; Becton Dickinson). Five blood samples were collected for each series of dosages. For q8h regimens, samples were collected just before and 30, 120, 270, and 480 min after the infusion onset. For q6h regimens, samples were collected just before and 30, 90, 210, and 360 min after the infusion onset. Panel A presents the concentration profiles for all the children included in the study. The open diamonds (right panel) indicate the imipenem plasma concentrations for a child who received a dose of 60 mg/kg/day (q8h) and failed to respond to therapy. Wide interindividual variations were observed. Panel B presents the concentration-time profiles for children who were <1 year old. Arrows in the right panel indicate children who were <1 month old. In spite of a decreased rate of imipenem elimination in very young children (1, 4, 21, 22), the concentration-time profiles were not markedly different from those for other children. Panel C depicts the concentration profiles of imipenem in a subset of children with impaired renal function, defined by creatinine clearance (ml/min × 1.73 m²) of <2 standard deviations for the age group (no cases requiring dialysis were included). Dotted lines represent approximations in a few cases where the last dosage was below the limit of quantification (i.e., 0.5 mg/liter). Note that since only a few points were taken during the first hour following administration, a precise distribution phase cannot be deduced from the figure.

FIG. 2.

Correlation between age or height and the volume of distribution at steady state (V_SS) in the study population. Each data point represents a single patient. Closed circles indicate patients who were <1 year old or had <70 cm in height. Open circles represent children with values above these respective cutoffs. There was a fracture between the two correlation curves at 1 year and/or 70 cm. Caution is warranted for data below these values, because both age and size are inversely correlated with V.