부산대학교 도서관

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. [ABSTRACT FROM AUTHOR]