Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Placebo-controlled Parallel Group, Phase II Dose-Ranging Study of Nebulized Amikacin Delivered Via the Pulmonary Drug Delivery System (PDDS) in Ventilated Patients With Nosocomial Pneumonia Due to Gram Negative Organisms
Brief Summary: This study is part of a research program too see if amikacin delivered as an aerosol directly to the lungs in combination with IV antibiotic therapy can help intubated patients with gram-negative pneumonia get better faster than when given intravenous antibiotics alone. The primary purpose of this study is to determine the correct dose of amikacin which is delivered directly to the lungs as an aerosol via an investigational device called the Pulmonary Delivery Device System (PDDS).


Options:
A: Inclusion Criteria:

1. Patients with clinically suspected or microbiologically confirmed bacterial sepsis
2. Informed consent

Exclusion Criteria:

1. Patients with microbiologically documented infections caused by the following microorganisms: Listeria spp, Legionella pneumophilia, Mycobacterium tuberculosis, Staphylococcus aureus
2. Patients with fungal infections
3. Patients with severe infections due to viruses or parasites (e.g. hemorrhagic fever, malaria)
4. Patients with suspected or confirmed bacterial meningitis or endocarditis
5. Patients with localized, deep-seated abscesses (e.g. brain abscess) without systemic sepsis
6. Patients with chronic, localized infections (e.g. chronic osteomyelitis) without systemic sepsis
7. Neutropenic and other severely immuno-compromised patients (patients infected with human immunodeficiency virus and a CD4 count \< 200; patients on immuno-suppressive therapy after solid organ transplantation; patients with cystic fibrosis)
8. Withholding of life-support
9. Early discharge or death (\< 24 hours after admission)
10. Complete absence of antimicrobial treatment despite suspicion of sepsis
B: Inclusion Criteria:

* Male and female patients 18 years of age or older with a clinical diagnosis of VAP, HAP or HCAP who are expected to be on mechanical ventilation for at least 3 days

Exclusion Criteria:

* Patients with compromised of suppressed immune systems, severe hypoxemia, PEEP\>15cm H2O, creatinine\>2 mg/dL, or who are pregnant
C: Inclusion Criteria:

* Patient hospitalised in the ICU
* Bacterial infection suspected
* At ICU admission the patient do not receive antibiotics or receive antibiotics for less than 24hours and an interval between admission and inclusion \< 12 hours
* During ICU stay, provided that the interval between the start of suspected infection and inclusion is \< 12hours
* Written inform consent from the patient or relatives. The consent may be obtained after the enrollment if the patient is not able to give consent and if there is no relatives

Exclusion Criteria:

* Age \< 18 years
* Pregnancy
* Patient expected to remain hospitalised in the ICU for less than 3 days
* Neutropenia
* Infection or presumed infection requiring prolonged antibiotic therapy (endocarditis,osteo-articular infection, mediastinitis, deep abscess, tuberculosis, pneumocystis pneumonia, toxoplasmosis).
* Simplified Acute Physiology Score II at ICU admission (calculated during the first 12h)
* Attending physician declining to use full life support.
D: Inclusion Criteria:

* Patients must have new or worsening radiographic infiltrates consistent with ventilator-associated pneumonia that was not related to cardiac or other disease processes
* Have at least 1 of the following: fever (core body temperature greater than 39.0°C); hypothermia (core body temperature of less than 35.0°C); leukocytosis (increased WBC count); and leukopenia (decreased WBC count)
* Have developed ventilator-associated pneumonia and have been on mechanical ventilation for more than or equal to 48 hours and on mechanical ventilation at the time that study medication is assigned
* Have been hospitalized or been in a chronic care facility for consecutive 5 days or more within the last 90 days
* Have a baseline Clinical Pulmonary Infection Score (CPIS) more than or equal to 6 and an Acute Physiology and Chronic Health Evaluation (APACHE) II score more than 8 and less than 35

Exclusion Criteria:

* Have received antibiotics for this episode of ventilator-associated pneumonia for more than 24 hours before study medication administration
* Known presence at baseline of only methicillin-resistant Staphylococcus aureus or Stenotrophomonas infection
* Acute respiratory distress syndrome
* Has any of the following conditions: chest trauma with severe lung bruising or loss of stability of the thoracic cage following a fracture of the sternum, ribs, or both, increased amounts of fluid in the lung cavities requiring drainage or pus in the cavity
* Has active seizure disorder within the last 2 years or brain injury such that imipenem cilastatin would not be administered to the patient in usual practice
* Has lung cancer within the last 2 years, chronic bronchitis with an increase in severity within the last 30 days, chronic enlargement of the bronchi or bronchioles related to inflammatory disease or obstruction, lung abscess(s), anatomical bronchial obstruction, respiratory tuberculosis on treatment, suspected atypical pneumonia, chemical pneumonitis, cystic fibrosis, congestive heart failure, severe burns to greater than 15% of the body, evidence of severe and chronic liver disease

Answer: B