Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study.

PURPOSE: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. METHODS: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L. RESULTS: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. CONCLUSION: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.

[Therapeutic effects of aspiration with a directional soft tube and conservative treatment on mild hemorrhage in the basal ganglion].

OBJECTIVE: To compare the therapeutic effects of aspiration via a directional soft tube and conservative treatment in patients with mild hemorrhage in the basal ganglion. METHODS: Seventy-five patients with mild cerebral hemorrhage (10~30 ml) were randomly divided into two groups for aspiration treatment with minimally invasive directional soft tube placement (minimally invasive group, n=36) and conservative treatment (medication group, n=39). The patients in the two groups had comparable mean GCS scores of 11-15 on admission. The clinical outcomes of the patients were compared between the two groups. RESULTS: In the minimally invasive group, complete removal or absorption of the hematoma occurred within an average of 3.8 days, significantly shortened in comparison with the 24 days in the medication group. The short-term (1 month) follow-up of the patients showed good neurological recovery in 58% of the patients in the minimally invasive group, significantly greater than the rate of 29% in the medication group; 6 months after the treatment, good neurological recovery was achieved in 50% of the patients in the minimally invasive group, but only 16% in the medication. No death occurred in the minimally invasive group, and 2 patients died in the medication group. The cost of hospitalization averaged 5136.3 Yuan in the minimally invasive group and 11843.6 Yuan in the medication group. CONCLUSION: Compared with conservative treatment, the minimally invasive treatment with soft tube placement can significantly shorten the hospital stay, promote neurological function recovery, lower the mortality rate, and reduce the cost of hospitalization.