Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome

Abstract

Objective Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. Design Prospective before-after study. Settings Intensive-care unit of a French teaching hospital and sickle cell disease referral center. Patients Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. Interventions Patients were treated with intermittent administration during the first period (April 2016 –April 2018) and with continuous infusion during the second period (May 2018 –August 2019). Measurements and main results We included 60 episodes of acute chest syndrome in 58 patients (29 [25–34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48–88] vs. 61 [57–64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4–13.3] vs. 0 [0–0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. Conclusion As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.