To Compare Safety and Efficacy of Doripenem Versus Imipenem-Cilastatin in Patients With Ventilator-Associated Pneumonia

• Clinical Cure Rate at the End-of-treatment (EOT) Visit [ Time Frame: End-of-treatment (Day 10 or Day 11) ] [ Designated as safety issue: Yes ]
  The number of patients who achieved clinical cure at the EOT visit on Day 10. The patient's were classified as clinical cure if they had resolution of signs and symptoms and objective findings of pneumonia to such an extent that no further antimicrobial therapy was necessary.
  
  

• Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom a Qualifying P. Aeruginosa Was Isolated at Baseline [ Time Frame: End-of-treatment (Day 10 or Day 11) ] [ Designated as safety issue: Yes ]
  The clinical cure rate at the EOT visit in patients, whose bronchoalveolar lavage (BAL) or mini-BAL culture results yielded qualifying pneumonia pathogen P. aeruginosa at baseline.
  
  
• Clinical Cure Rate at the End-of-treatment (EOT) Visit in Patients From Whom at Least 1 of the Gram-negative Qualifying Pneumonia Pathogens (Enterobacteriaceae, P. Aeruginosa, and Acinetobacter Spp) Was Isolated at Baseline [ Time Frame: End-of-treatment (Day 10 or Day 11) ] [ Designated as safety issue: Yes ]
  The clinical cure rate at the EOT visit in patients whose BAL or mini-BAL culture results yielded at least 1 of the following Gram-negative qualifying pneumonia pathogens was isolated at baseline: any Enterobacteriaceae, P. aeruginosa, and Acinetobacter Spp.
  
  
• Number of Patients Who Had Emergence of P. Aeruginosa Resistance [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
  Number of patients who had P. aeruginosa isolates with a 4 fold or greater increase in minimum inhibitory concentration (MIC) at anytime during the study (after the study medication is received) from baseline
  
  
• 28-day All-cause Mortality Rate [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  Number of deaths which occured up to 28 days of the study period due to all causes
  
  

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), active-controlled (agent that is compared with a study medication to test whether the study medication has a real effect in a clinical study), double-dummy (placebo [inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study] is administered to maintain the blind when the comparator medication cannot be made identical to the study medication), parallel-group (each group of patients will be treated at the same time), multicenter study to assess the effectiveness and safety of 7 day course of doripenem, compared with 10 day course of imipenem-cilastatin in patients with ventilator-associated pneumonia. This study will consists of 3 phases: (1) a pretreatment phase with a maximum of 24 hours for the screening/baseline visit, (2) a double blind, double dummy, treatment phase of 10 days (Day 1 to Day 10) and an end-of-treatment (EOT) assessment within 24 hours after the last dose of study medication therapy administered on Day 10 or at the time of early withdrawal from study medication, and (3) a post treatment (follow-up) phase consisting of an early follow-up (EFU) visit within 7 to 14 days after the last dose of study medication, and last follow-up (LFU) visit within 28 to 35 days after the last dose of study medication for all patients including those who discontinued study medication early. Two hundred and seventy four patients will be randomly assigned to receive either doripenem or imipenem with placebo of the other medication given simultaneously to maintain the blind (eg, 1 group will receive blinded doripenem from Days 1 to 7 and imipenem placebo Days 1 to 10, other group will receive blinded imipenem Days 1 to 10 and doripenem placebo Days 1 to 7). A sample of secretions from the lower respiratory tract will be obtained by bronchoalveolar lavage (BAL) or mini-BAL within 36 hours prior to administration of study medication from the enrolled patients and sent for culture. Patients, whose baseline BAL or mini-BAL culture results will yield at least 1 qualifying pneumonia pathogen will continue to receive study medication therapy and patients, whose baseline BAL or mini-BAL culture results did not yield at least 1 qualifying pneumonia pathogen will be discontinued from study medication therapy but will remain enroll in the study and will be followed for safety. Safety evaluations including adverse events, clinical laboratory evaluations, vital signs and physical examinations will be monitored throughout the study period. The total duration of an individual patient's participation in the study will be approximately 5 to 6 weeks.