Bacteriemia and Pneumonia due to Pseudomonas aeruginosa
Conditions
Interventions
Trade Name: Colistimetato de Sodio
Product Name: Colistimetato de sodio
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: COLISTIN
CAS Number: 1066-17-7
Concentration unit: mg
Sponsors
Consorci Parc de Salut Mar de Barcelona
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Both gender, aged 18 years old patients at time of the screening visit. 2. Patients with bacteremia and /or pneumonia due to extremely resistant P. aeruginosa with reduced sensitivity to meropenem and colistin susceptible that require treatment with colistine at physician criterion. In the case of bacteremia it would be enough with one positive blood culture for that type of P. aeruginosa. Pneumonia is defined with the following diagnostic criteria: 2.1 Acute onset of at least 3 of the following signs and symptoms (new or worsening) a. Cough. b . Purulent sputum. c . Dyspnea. d . Chest pain due to pneumonia. 2.2 At least 1 of the following: a. Fever: defined as an axillary temperature superior or equal than 38 ° C b . Hypothermia is defined as an axillary temperature minor than 35 ° C c . Rales on lung auscultation and/or evidence of pulmonary consolidation (dullness to percussion , bronchial breath sounds or egophony) . 2.3 Presence of parenchymal infiltrates lobar, multilobar or compatible with an acute bacterial pneumonia in a lung study (example: chest radiography preferably posteroanterior and lateral, one plane is acceptable if it is conclusive; or computed tomography of chest) in the 48 hours prior to first dose of study drug. The researcher can interpret the imaging study to decide whether the patient is suitable for inclusion. Patients with ventilator-associated pneumonia may also be included. 3. Significant culture of respiratory samples will be considered as the presence of extremely resistant P. aeruginosa sputum culture of good quality (grade V: more than 25 polymorphonuclear leukocytes per field, and less than 10 epithelial cells or grade IV: over 25 polymorphonuclear leukocytes per field and 10-25 epithelial cells per field), or bronchial aspirate with more than 104 CFU/mL, or bronchoalveolar lavage with more than 103 CFU/mL or telescoping catheter culture with more than 103 CFU / mL. The presence of positive blood cultures for P. aeruginosa extremelyresistant in a patient with pneumonia it will be attributable to pneumonia in absence of other apparent source although cultures of respiratory samples are negative. 4. Patients able to understand study implications and demonstrate thus signing the informed consent voluntarily. The unconscious patients may participate in the trial whenever a family member or legal representative sign the informed consent designed for this purpose. 5. Patients of childbearing potential must have a negative pregnancy test. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1. Allergy to penicillin or colistin, or hypersensitivity to the active principle or any of drug study. 2. Epilepsy. 3.Pregnant or breast feeding. 4. Participation in any other clinical trial at 3 months prior to administration of the drug. 5. Colonization without infection. 6. Any other concomitant infection. 7. Polymicrobial bacteremia. 8. Las neumonías In: simultaneous cultivate for more germs. 9.In neumony: other not infectious Causes of pulmonary infiltration (heart failure, pulmonary thromboembolism, active pulmonary cancer). 9. Patient in terminal situation. 10. Renal failure that requieres substitutive treatment. 11. Antimicrobial active treatment active during more than 72 hours. 12. Women in fertile age and sexually active not able to use anticonceptive methods. 13. Any concomitant conditions that, in opinion of the investigator, could interfere at the study conduction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the superiority in efficacy of intravenous colistin combination with intravenous meropenem treatment for pneumonia or bacteremia due to extremely resistant Pseudomonas aeruginosa with reduced sensitivity to meropenem, as measured by clinical and microbiological cure at 5-7 days after completion of therapy (test of cure).;Secondary Objective: ? To compare mortality at 30 days and hospital stay ? To compare the incidence of toxicity ( safety ). ? Analyze the plasma levels of colistin, colistimethate sodium , meropenem and if , in the patients studied , at different times of the treatment cycle and correlate with clinical and microbiological response and toxicity. ? Study the MICs of colistin and meropenem in strains from patients. Relate these initial MICs with the final outcome ( clinical and microbiological cure and mortality ) . ? Analyze interactions in vitro of antibiotics used alone and in combination against isolates ( synergy test ) . ? Analyze the bactericidal power of the serum of the patients and correlate with clinical and microbiological response . ? Describe the molecular epidemiology and mechanisms of resistance of P. aeruginosa strains isolated from extremely resistant patients.;Timepoint(s) of evaluation of this end point: At 5-7 days after completion of therapy (test of cure ).;Primary end point(s): The primary endpoint is the rate of clinical and microbiological cure at 5-7 days after completion of therapy (test of cure ). Clinical cure it's defined as resolution of all symptoms of bacteremia and / or pneumonia who were present at the time of extraction of blood or respiratory cultures initial samples. Specifically bacteremia in clinical cure includes the resolution of fever (axillary temperature > 38 ° C ) if present, and the initial symptoms of the outbreak originating in bacteremia. In patients with clinical cure pneumonia include resolution of respiratory and systemic symptoms and the PaO2/FiO2 ratio is stable or | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -To compare mortality at 30 days and hospital stay. -To compare the incidence of toxicity (safety). -Analyze the plasma levels of colistin, colistimethate sodium, meropenem and where appropriate, at different times of the treatment cycle and correlate with clinical and microbiological response and toxicity. -Study the MICs of colistin and meropenem in strains from patients. Relate these initial MICs with the final outcome (clinical and microbiological cure and mortality). -Analyze interactions in vitro of antibiotics used alone and in combination against isolates (synergy test). - Analyze the serum bactericidal and correlate with clinical and microbiological response. -Describe the molecular epidemiology and mechanisms of resistance of strains of P. aeruginosa isolated extremely resistant. - Adverse events during treatment (nefrotoxicity/neurotoxicity/diarrhoea per Clostridium difficile).;Timepoint(s) of evaluation of this end point: At the first 30 days. | — |
Countries
Spain
Contacts
Public ContactServicio Enfermedades Infecciosas
Hospital del Mar
Outcome results
None listed