The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Comparison of trajectories of self-monitored glucose levels by hypoglycemia status over 52 weeks of treatment with insulin glargine or exenatide once weekly.

BACKGROUND: Self-monitoring of blood glucose (SMBG) is used as a means to detect and prevent hypoglycemia in patients with diabetes. However, information on the longitudinal measures (trajectory) of SMBG-based pre- and postprandial glucose fluctuations over time in relation to hypoglycemia is limited. Among patients treated with exenatide once weekly (EQW) or insulin glargine (IG), this study compared SMBG profiles over 52 weeks between patients who did and did not experience hypoglycemia. METHODS: Pooled patient-level 52-week longitudinal data of treatment with EQW (n = 531) or IG (n = 219) from three controlled trials were analyzed. RESULTS: The proportion of patients with at least one episode of hypoglycemia in the EQW and IG groups was 23% and 54%, respectively. The preprandial glucose measures from SMBG were significantly lower among patients who experienced hypoglycemia in both treatment groups compared with those who did not. In patients who experienced hypoglycemia, the average preprandial glucose levels over 52 weeks were lower by 0.64 and 0.66 mmol/L in the EQW and IG groups, respectively (P < 0.01 in both cases) compared with those without hypoglycemia. The average postprandial levels were not significantly different between patients who did and did not experience hypoglycemia in both treatment groups. Among patients with hypoglycemia, the average prebreakfast glucose trajectory was higher by 0.48 mmol/L in the EQW compared with the IG group. CONCLUSIONS: This study has revealed differential trajectories of pre- and postprandial glucose profiles between patients with and without hypoglycemia. However, the SMBG trajectories were similar between patients treated with EQW and IG.