Effect of targeted, strong antibiotic therapy and duration of therapy on the development of resistance of bacteria against antibiotics during the treatment of in-patients with pneumonia which need mechanical ventilatio

• Conditions: Pneumonia; MedDRA version: 14.1Level: PTClassification code 10060946Term: Pneumonia bacterialSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2012-003483-46-ES
• Lead Sponsor: niversity of Florida Board of Trustees

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10-18
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

1. Provision of written informed consent by the subject or subject's legal representative.
2. Hospitalized males or females, 18 years or older, with respiratory failure requiring mechanical ventilation and clinical suspicion of HABP, HCAP or VABP.
3. Onset or exacerbation of pneumonia at least 72 hours after admission to an acute care facility or onset of pneumonia in a nursing home or rehabilitation facility with subsequent transfer to an acute care facility (HCAP definition: and as defined in Inclusion criteria 6, 7, and 8).
4. Women of childbearing potential may be entered if their pregnancy test (urine or serum) is negative, and they are instructed to abstain from sexual intercourse for the duration of the study, or contraceptive measures are used until all follow-up procedures are complete. Medically acceptable contraceptives include: (1) surgical sterilization, (2) approved hormonal contraceptives as advised by your study doctor (such as birth control pills, Depo-Provera, or Lupron Depot), (3) two barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD).
5. Subjects who have received previous antibacterial therapy within 14 days of pre-treatment bronchoscopy entry may be entered only if the subject has not responded clinically (as defined in Inclusion Criteria 6, 7, and 8).
6. Patients should have the following clinical findings that support a diagnosis of HABP/VABP/HCAP:
-Documented fever, defined as an oral or tympanic temperature greater than or equal to 38.0 degrees Celsius (100.4 degrees Fahrenheit), or a core temperature greater than or equal to 38.3 degrees Celsius (101 degrees Fahrenheit) or hypothermia, defined as a core body temperature of less than 35 degrees Celsius (95.2 degrees Fahrenheit); axillary temperatures are not recommended.
-An elevated total peripheral white blood cell (WBC) count (WBC greater than 10000/mm3); or greater than 15 percent immature neutrophils (bands), regardless of total peripheral WBC count; or leukopenia with total WBC less than 4500/mm3.
-New onset of expectorated or suctioned respiratory secretions characterized by purulent appearance indicative of bacterial pneumonia.
In addition, patients with HABP should have at least one of the following present at enrollment:
-A new onset of cough (or worsening of baseline cough) during 48 or more hours of hospitalization or within 7 days after discharge from a hospital.
-Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (e.g., dullness on percussion, bronchial breath sounds, or egophony).
-Dyspnea, tachypnea, or respiratory rate greater than 30/minute, particularly if any or all of these signs or symptoms are progressive in nature:
-Hypoxemia (e.g., a partial pressure of oxygen less than 60 mm Hg while the patient is breathing on room air as determined by arterial blood gas or oxygen saturation less than 90 percent while the patient is breathing on room air as determined by pulse oximetry, or worsening of the ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2), respiratory failure requiring mechanical ventilation).
7. Radiographic Findings: Within 48 hours before starting empiric therapy a subject's chest radiograph should show the presence of a NEW or progressive infiltrate, cavitation, or effusion suggestive of pneumonia.
8. Microbiologic Findings: Within 24 hours before the start of empiric study th

Exclusion Criteria

1. Subjects with pneumonia caused by pathogens resistant to meropenem (MIC >16?g/ml) or a prior meropenem therapy failure.
2. Subjects with contra-indications to ANY study medication, in particular with known or suspected allergy or hypersensitivity. This is inclusive of type I hypersensitivity (e.g., anaphylaxis) to cephalosporins, penicillins, monobactams, or carbapenems, and to vancomycin or linezolid.
3. Women who are pregnant or lactating.
4. Subjects taking anticonvulsant medications for a known seizure disorder.
5. Subjects with known or suspected community acquired bacterial pneumonia (CABP) or viral pneumonia; or Subjects with acute exacerbation of chronic bronchitis without evidence of pneumonia.
6. Subjects with primary lung cancer or another malignancy metastatic to the lungs.
7. Subjects who were previously enrolled in this study.
8. Subjects who have had an investigational drug or have used an investigational device within 30 days prior to entering the study.
9. Subjects with another focus of infection requiring concurrent antibiotics (e.g. other broad spectrum agents or those agents providing gram negative coverage) that would interfere with evaluation of the response to study drug.
10. Subjects with cystic fibrosis, acquired immune deficiency syndrome (AIDS) with a CD4 lymphocyte count <200 cells/µl, neutropenia (absolute neutrophil count <500 cells/ml), known or suspected active tuberculosis.
11. Subjects with little chance of survival for the duration of study therapy (7-14 days) because of antecedent illness or underlying comorbidities.
12. Subjects with an APACHE II score >35.
13. Subjects with underlying condition(s) which would make it difficult to interpret response to the study drugs.
14. Subjects with hypotension (systolic BP of < 85mmHg) or acidosis (arterial pH <7.25 or serum bicarbonate <15 mg/dl) despite attempts at fluid resuscitation. Subjects requiring ongoing treatment with vasopressors will be eligible for the study if their hypotension is controlled and acidosis has resolved. Subjects with intractable septic shock are not eligible for enrollment.
15. Subjects who have undergone bone marrow transplantation.
16. Subjects with profound hypoxia as defined by a PaO2/FiO2 ratio <100.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified