Pharmacokinetics of High-dose Tigecycline in Critically Ill Patients

Study Overview
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Brief Summary
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The objective of this study is to describe the pharmacokinetics of tigecycline in critically ill patients receiving continuous venovenous haemodialysis (CVVHD) and to evaluate the frequency of pharmacokinetic/pharmacodynamic target attainment with high dosing strategy (200 mg loading dose and 100 mg/12h).

Detailed Description
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This is a prospective observational study performed on critically ill patients. Inclusion criteria are: severe sepsis on admission requiring broad-spectrum antibiotics. Both medical and surgical patients will be included. Any type of infections will be included (pulmonary, abdominal, urinary tract, etc.) Antibiotics regimen includes: tigecycline (200 mg every 12 hours intravenously), meropenem (2 grams every 8 hours intravenously). Blood samples (3 mL) will be collected 2, 4, 8 and 12 hours after each dose of tigecycline for 3 consecutive days. The standard arterial canula will be used to obtain samples. In each case CVVHD will be started and continued for at least 3 days' period. 30 minutes after a collection each sample will be centrifuged for 10 minutes at 3,000 rpms. Subsequently, supernatant will be collected and frozen. Serum tigecycline concentration will be measured with high performance liquid chromatography. Each patient's hemodynamics parameters will be recorded with the use of transpulmonary thermodilution technique (PICCO). Other therapies i.e.: ventilatory support, sedation, an antifungal agent will be given as required.

Official Title
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Pharmacokinetics of High-dose Tigecycline in Critically Ill Patients: an Observational, Prospective Study

Conditions
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Septic Shock, Antibiotic Resistant Infection, Critical Illness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who require ICU treatment due to severe sepsis age 18-80 years CVVHD treatment an eligible consent obtained from the patient or his/her attendant Exclusion Criteria: allergy to tigecycline or meropenem contraindication to CVVHD lack of consent to participate in the study age of patients below 18 or above 80 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| tigecycline<br>Each patient will receive: tigecycline (200 mg q 12 hours i.v.), meropenem (2 g q 8 hours i.v). In each case CVVHD will be started. Blood samples (3 mL) will be collected 2, 4, 8 and 12 hours after each dose of tigecycline for 3 consecutive days. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of tigecycline | Samples obtain from ICU patients 2, 4, 8 12 hours after each dose of tigecycline for 3 days. | 72 hours for each patient from the tigecycline treatment initiation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tigecycline, pharmacokinetics