A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: Intermittent, short infusion Ticarcillin-clavulanateDrug: Continuous infusion Ticarcillin-clavulanateDrug: Intermittent, short infusion Cefepime
- Registration Number
- NCT01667094
- Lead Sponsor
- The Alfred
- Brief Summary
Cystic fibrosis (CF) is an inherited disorder which results in increased thickness of secretions, especially in the lungs. By adulthood, the majority of patients with CF will have a bacteria living in their lungs, called Pseudomonas aeruginosa which can cause lung infections. This usually results in worsening respiratory symptoms and often an acute deterioration in their lung function. They are usually treated with antibiotics that target the Pseudomonas aeruginosa. These antibiotics are typically given as short intravenous infusions several times a day. This study aims to compare the standard method of giving these antibiotics with a different strategy of giving these antibiotics to see if this can improve the outcomes of treatment of these infections and reduce the amount of Pseudomonas aeruginosa in the lungs of these patients. This strategy consists of giving the same antibiotics continuously, to ensure there is always enough antibiotic in the bloodstream and the lung to be able to kill the bacteria.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
-
Patients >= 18 years of age,
-
Pseudomonas aeruginosa isolated in sputum within the last 12 months,
-
has an acute infective exacerbation, defined by international standards of 2 or more of the following in the last 2 weeks:
- change sputum volume or colour,
- increased cough,
- increased dyspnoea,
- increased malaise, fatigue or lethargy,
- anorexia or weight loss,
- decrease in pulmonary function by 10% or more, or
- new radiographic changes
- patients < 18 yrs of age,
- patients that do not meet the criteria for an acute infective exacerbation,
- concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
- impaired renal function with an estimated creatinine clearance < 60 mls/min,
- patients allergic to ß-lactam antibiotics,
- aminoglycoside contra-indicated,
- intravenous antibiotics in the last 2 weeks, prior to this admission,
- received more than 24 hours of intravenous antibiotics in this admission,
- previous lung transplantation,
- pregnancy or lactation, or
- inability to consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Intermittent, short infusion Intermittent, short infusion Ceftazidime Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician Intermittent, short infusion Intermittent, short infusion Ticarcillin-clavulanate Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician Intermittent, short infusion Intermittent, short infusion Cefepime Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician Intermittent, short infusion Intermittent, short infusion Piperacillin tazobactam Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician Continuous infusion Continuous infusion Ceftazidime Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician Continuous infusion Continuous infusion Ticarcillin-clavulanate Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician Continuous infusion Continuous infusion Meropenem Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician Continuous infusion Continuous infusion Cefepime Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician Continuous infusion Continuous infusion Piperacillin tazobactam Continuous infusion of either: Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g Antibiotic chosen by treating physician Intermittent, short infusion Intermittent, short infusion Meropenem Infusion over 30 minutes of either: Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24 Antibiotic chosen by treating physician
- Primary Outcome Measures
Name Time Method Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score Day 0 to Day 14
- Secondary Outcome Measures
Name Time Method Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa) Day 0 to Day 3, Day 0 to Day 7 Measured by PCR.
C-reactive peptide (CRP) Day 0 to Day 3 Time above minimum inhibitory concentration (MIC) Day 3 Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score Day 0 to Day 7, Day 0 to Day 28 Lung function testing; Forced volume expired in one second (FEV1) Day 0 to Day 7, Day 0 to Day 28 Antibiotic stability Day 3 For ceftazidime and meropenem, antibiotic levels will be measured from the infusion bag at the beginning and end of the infusion to determine the amount of degradation of these antibiotics.
The temperature of the infusion bags will be monitored continuously during this time.Pseudomonas aeruginosa virulence gene determinants Day 0 to Day 3 and Day 0 to Day 7 A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.
Trial Locations
- Locations (1)
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia