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).

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.

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

Patients admitted to ICU due to severer sepsis recognition. Both medical and surgical patients will be included. Any site of infection will be treated in the manner.

In each case CVVHD will be initiated and continued. Each patient will receive 200 mg tigecycline q 12h, 2 g meropenem q 8 h. Other treatment as required.