Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis.

BACKGROUND: Doripenem is approved by the Food and Drug Administration for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections. While studies have described the pharmacokinetics/pharmacodynamics (PK/PD) of doripenem in the critically ill, no study has described the probability of target attainment profile among trauma patients with sepsis. PATIENTS AND METHODS: This study was a prospective, open-label, pharmacokinetic study in the surgical intensive care unit (SICU) at Grady Health System. Thirty trauma patients with sepsis admitted to the SICU received doripenem 1 g infused over 4 hours every 8 hours for three doses. Blood samples were taken just before and after the third dose. A two-compartment model was fit to the data using non-parametric population PK modeling software. Embedded with the final PK model, a Monte Carlo Simulations (MCS) was performed to determine the PK/PD profile of doripenem 1 g, infused over 4 hours, every 8 hours after administration of the first and fourth doses. RESULTS: Overall, the model fit the data well, and mean (standard deviation) clearance and volume of the central compartment were 16.9 (11.4) L/h and 28.5 (16.0) L, respectively. In the MCS analyses, doripenem 1 g, infused over 4 hours, administered every 8 hours, conferred >90% probabilities of achieving 30-50% time greater than the minimum inhibitory concentration (30-50% T>MIC) for MICs ≤2 mg/L after infusion of both the first and fourth doses. The MCS indicated that more intensive doripenem dosing schemes should be considered for organisms with MIC values in excess of 2 mg/L. CONCLUSIONS: This is the first study to describe the doripenem PK/PD in critically ill patients with trauma. Among these patients, the MCS analyses suggest that current dosing strategies may be ineffective when the MIC value for the infecting pathogen is expected to be above 2 mg/L.

Impact of a hyperglycemic crises protocol.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of an adult hyperglycemic crises protocol based upon the 2009 American Diabetes Association (ADA) consensus statement. METHODS: We performed a retrospective review of patients treated before and after protocol implementation at a university teaching hospital. A total of 256 adult patients met the criteria for diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) and were treated with an insulin infusion between February 2011 and February 2012 (nonprotocol n = 143, protocol n = 113). Protocol efficacy was evaluated by assessing time to resolution of DKA or HHS, length of stay (LOS) in the intensive care unit (ICU), and LOS in the hospital. Protocol safety was evaluated by assessing the numbers of patients with hypoglycemic and hypokalemic events. RESULTS: Patients on the hyperglycemic crises protocol experienced a 9.2 hour (95% confidence interval (CI): 4.70-13.70; P<.001) decrease in time to resolution, with nonprotocol patients (n = 143) resolving in 22.78 hours and protocol patients (n = 113) resolving in 13.58 hours. There was no difference in safety outcomes, including the number of patients with moderate hypoglycemia (blood glucose <70 mg/dL), severe hypoglycemia (blood glucose <50 mg/dL), or hypokalemia (K+ <3.3 mmol/L). CONCLUSION: Implementation of a hyperglycemic crises protocol decreased times to resolution of DKA and HHS without increasing the rate of hypoglycemia or hypokalemia.