Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection

Inclusion Criteria: 1. Males and non-pregnant, non-lactating females, 18 years of age or older 2. Currently intubated and mechanically-ventilated subjects in the ICU 3. Suspicion of lower respiratory tract infection 4. Presence of Gram-negative organism(s) by Gram stain OR by culture of pre-therapy respiratory specimen (eg, endotracheal aspirate \[ETA\], bronchoalveolar lavage \[BAL\], or mini-BAL) OR previous colonization 48 h before screening. 5. Initial empiric antimicrobial meropenem regimen 6. At least two risk factors for multidrug-resistant organisms 7. Provision of written informed consent by the subject or a family member or a close relative or waiver of consent. Exclusion Criteria: 1. Subjects who have received antibiotic therapy for Gram-negative LRT infection for ≥ 36 hours at the time of randomization 2. Subjects with known or suspected type 1 hypersensitivity to beta-lactam and/or cephalosporin 3. Subjects taking valproic acid for a seizure disorder 4. Subjects who have had a left hemisphere stroke within five days and there is an increased risk of fatal brain oedema 5. Subjects who have cystic fibrosis, human immunodeficiency virus (HIV) infection with CD4 count \<100 cell/mm3 or invasive fungal infection of the lung 6. Neutropenia (ANC \< 103 neutrophils/mm3) 7. Bone marrow transplant. 8. Subjects who have been on mechanical ventilation for \>28 days