Pharmacodynamics Study of Imipenem in Patients With Ventilator Associated Pneumonia

The Pharmacodynamics of Imipenem in Critically Ill Patients With Ventilator-associated Pneumonia Following Administration by 4 h or 0.5 h Infusion

Imipenem is a carbapenem antibacterial agent with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. This agent is often used as the last line of therapy for highly resistant Gram negative bacilli nosocomial infections. In common with other beta-lactamase inhibitor, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with the therapeutic efficacy is the time that concentrations in the tissue and serum are above the MIC and administration by continuous infusion is the preferred mode of administration to maximize this parameter. However, in tropical countries, the stability of carbapenem antibiotics is an important consideration when considering continuous infusion. Therefore, prolonged infusion may be a useful mode of administration to maximize bactericidal activity. This study will demonstrate the stability of imipenem in clinical use at room temperature in tropical countries.

Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 0.5 hr infusion of 0.5 g every 6 hr of imipenem at room temperature

Each patient will receive a loading dose of 0.5 g 3 min infusion followed by 4 hr infusion of 1 g every 8 hr of imipenem at room temperature

- To determine plasma Imipenem PK/PD parameters (the PK/PD index (T>MIC), the probability of target attainment (PTA) at 40% (T>MIC), the cumulative fraction of response (CFR))after 4 hr infusion of 1 gm every 8 hr compared to 0.5 hr infusion of 0.5 gm every 6 hr. Conventional arm: after first dose, blood samples will be obtained by direct venepuncture at: time 0, 0.5, 6, 6.5, 12, 12.5, 18, 18.25, 18.5, 18.75, 20, 21, 22 and 24 hr Extended infusion arm: after first dose, blood samples will be obtained by direct venepuncture at: time 0, 4, 8, 12, 16, 16.5, 17, 18, 20, 20.5, 21, 22, and 24 hr

Inclusion Criteria: Patients aged > or = 20 years Patients who have VAP with Gram negative bacilli infections which are sensitive to imipenem by the disk diffusion Exclusion Criteria: Patients who have documented hypersensitivity to imipenem or other carbapenems Patients who have an estimated creatinine clearance of < or = 60 ml/min Patients who are in circulatory shock Patients who are pregnant

Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine, Prince of Songkla University