Cystic Fibrosis
Conditions
Keywords
Pulmonary exacerbation, Continuous infusion, Antipseudomonal beta-lactams
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.
Interventions
DRUGIntermittent, short infusion Ceftazidime
Ceftazidime 1g q8/24
DRUGContinuous infusion Ceftazidime
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
DRUGIntermittent, short infusion Meropenem
Meropenem 1g q8/24, infusion over 30 minutes
DRUGContinuous infusion Meropenem
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
DRUGIntermittent, short infusion Ticarcillin-clavulanate
Ticarcillin/clavulanate 3.1g q6/24
DRUGContinuous infusion Ticarcillin-clavulanate
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
DRUGIntermittent, short infusion Cefepime
Cefepime 1g q8/24
DRUGContinuous infusion Cefepime
Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24
DRUGContinuous infusion Piperacillin tazobactam
Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24
DRUGIntermittent, short infusion Piperacillin tazobactam
Piperacillin tazobactam 4.5g q6/24
Sponsors
The Alfred
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients \>= 18 years of age, 2. Pseudomonas aeruginosa isolated in sputum within the last 12 months, 3. 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
Exclusion criteria
1. patients \< 18 yrs of age, 2. patients that do not meet the criteria for an acute infective exacerbation, 3. concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure, 4. impaired renal function with an estimated creatinine clearance \< 60 mls/min, 5. patients allergic to ß-lactam antibiotics, 6. aminoglycoside contra-indicated, 7. intravenous antibiotics in the last 2 weeks, prior to this admission, 8. received more than 24 hours of intravenous antibiotics in this admission, 9. previous lung transplantation, 10. pregnancy or lactation, or 11. inability to consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score | Day 0 to Day 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lung function testing; Forced volume expired in one second (FEV1) | Day 0 to Day 7, Day 0 to Day 28 | — |
| C-reactive peptide (CRP) | Day 0 to Day 3 | — |
| Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa) | Day 0 to Day 3, Day 0 to Day 7 | Measured by PCR. |
| Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score | 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. |
| Time above minimum inhibitory concentration (MIC) | Day 3 | — |
Countries
Australia
Outcome results
None listed