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

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 de...

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Veröffentlicht in:Surgical infections Jg. 17; H. 6; S. 675
Hauptverfasser: Rahbar, Aryan J, Lodise, Thomas P, Abraham, Prasad, Lockwood, Alissa, Pai, Manjunath P, Patka, John, Rabinovich, Marina, Curzio, Karen, Chester, Katleen, Williams, Brian, Morse, Bryan, Chaar, Mitchell, Huang, Vanthida, Salomone, Jeffrey
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.12.2016
Schlagworte:
Adult
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Carbapenems - pharmacokinetics
Carbapenems - pharmacology
Carbapenems - therapeutic use
Critical Illness
Female
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Prospective Studies
Sepsis - complications
Sepsis - drug therapy
Wounds and Injuries - complications
trauma
pharmacokinetics
carbapenem
doripenem
pharmacodynamics
sepsis
ISSN:1557-8674, 1557-8674
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Zusammenfassung: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. 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. 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. 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.
Bibliographie:ObjectType-Article-1
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content type line 23
ISSN:1557-8674
1557-8674
DOI:10.1089/sur.2015.113