Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Phase II Study of High Dose Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation

Inclusion of patients undergoing mechanical ventilation and presenting a pneumonia in order to determine serum pharmacokinetics of nebulized amikacin. The primary aim is to determine the dose of amikacin to be nebulized in order to observe amikacin serum concentrations close to but inferior to those observed after standart intravenous amikacin infusion.

After inclusion, patients undergo intravenous infusion of 20 mg/Kg of amikacin with amikacin serum concentrations being monitored over the following 24 hours.

Randomization occures after this first amikacin infusion. Patients are randomized to group nebulized amikacin or intravenous amikacin. The three next days of the study patients recieve nebulized amikacin (or nebulized placebo) during mechanical ventilation and a placebo infusion (amikacin infusion in case of placebo nebulization) using a air driven jet nebulizer. Amikacin serum concentrations are monitored over 24 hours after each nebulization.

Patients are followed up during 10 days for safety and efficacy. The dose of amikacin to be nebulized is 60 mg/Kg for the first 6 patients (phase A), 80 mg/Kg for the next 6 patients (phase B) and 100 mg/Kg for the last 6 patients (phase C). Each phase is started after review of the results of the preceeding phase by an idependent safety and monitoring board.

Inclusion Criteria:

• Patients admitted to intensive care unit.
• Patients undergoing mechanical ventilation for more than 48H.
• Suspicion of ventilator associated pneumonia.

Exclusion Criteria:

• Allergy to amikacin or any compound of the medication.
• Body mass index > 30 kg/m2.
• Myasthenia gravis.
• Acute or chronic renal failure.
• Vestibulo-cochlear disease.
• Pregnancy.
• Brain death.