Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Continuous infusion, Pharmacokinetics
Brief summary
At the Department of Infectious Diseases, Aarhus University Hospital, continuous infusion with piperacillin/tazobactam for a period of 2 weeks, has been used for several years in patients with cystic fibrosis, suffering from acute pulmonary exacerbations (APE). It is an outpatient treatment. To assess the efficacy and quality of the treatment, a blood test every 3rd day is taken to determine the concentration of Piperacillin in blood-plasma.
Detailed description
Patients with cystic fibrosis (CF) are often colonized with multidrug-resistant microorganisms, which increases the risk of suboptimal dosing of antibiotics as the time above the minimum inhibitory concentration (T\>MIC) is suboptimal. Continuous infusion of beta-lactam antibiotics is more likely to optimize T\>MIC than intermittent infusion. At the Department of Infectious Diseases, Aarhus University Hospital, continuous infusion with piperacillin/tazobactam for a period of 2 weeks, has been used for several years in patients with CF, suffering from acute pulmonary exacerbations (APE). It is an outpatient treatment, and the patients are given 16 g of piperacillin per 24 hours. To assess the efficacy and quality of the treatment, a blood test every 3rd day will be required to monitor the blood-plasma concentration of piperacillin, as well as C-reactive protein (CRP) and white blood cell count (WBC).
Interventions
None listed
Sponsors
University of Aarhus
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patients with Cystic Fibrosis, suffering from acute pulmonary exacerbations, treated with continuous infusion of Piperacillin/Tazobactam for a period of two weeks.
Exclusion criteria
* Age under 18
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood-plasma Concentration of Piperacillin | Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatment | The free, non-protein bound fraction of plasma piperacillin for each patient was determined using Ultra High Performance Liquid Chromatography. The concentration was compared to the MIC-value (Minimal Inhibitory Concentration) of the pathogen isolated in a sputum sample collected prior to initiation of antibiotic treatment. Infusion pumps with 16 g of piperacillin per 24 hours were initially used and five patients had piperacillin plasma-concentrations monitored during this treatment regimen. However, in three of these patients, the piperacillin plasma concentrations were unexpectedly low and dropped to a level below the MIC. This was found to be due to antibiotic crystallization within the infusion pumps as a result of the antibiotic concentration being too high. Consequently, infusion pumps with 12 g of piperacillin per 24 hours were used in stead. The median piperaillin concentrations reported below are derived from all measurements within the two weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Time Above the Minimum Inhibitory Concentration (T>MIC) | Patients will be followed for the duration of treatment, which is approximately 2 weeks. | The time, expressed in percentage, for which the plasma concentration of Piperacillin lies above the minimum inhibitory concentration for the pathogen,during the treatment. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%. MIC for the pathogen in sputum was not reported in patient 5. Therefore,T\>MIC for this patient could not be estimated. Patient 1-5 were treated with piperacillin 16g/day. Patient 6-10 were treated with piperacillin 12g/day. |
| MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | Sputum sample was collected 3 to 7 days before treatment initiation. | MIC to piperacillin/tazobactam was obtained by using E-tests (AB Biodisk, Solna, Sweden) on Mueller-Hinton agar plates incubated at 35 ± 2 degrees Celcius with inoculum, incubation time and atmosphere in accordance to the E-test application guide. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pharmacokinetics Piperacillin Patients with cystic fibrosis and pulmonary exacerbation, treated with Piperacillin/Tazobactam, given as continuous infusion for a period of two weeks. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Pharmacokinetics Piperacillin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Blood-plasma Concentration of Piperacillin
The free, non-protein bound fraction of plasma piperacillin for each patient was determined using Ultra High Performance Liquid Chromatography. The concentration was compared to the MIC-value (Minimal Inhibitory Concentration) of the pathogen isolated in a sputum sample collected prior to initiation of antibiotic treatment. Infusion pumps with 16 g of piperacillin per 24 hours were initially used and five patients had piperacillin plasma-concentrations monitored during this treatment regimen. However, in three of these patients, the piperacillin plasma concentrations were unexpectedly low and dropped to a level below the MIC. This was found to be due to antibiotic crystallization within the infusion pumps as a result of the antibiotic concentration being too high. Consequently, infusion pumps with 12 g of piperacillin per 24 hours were used in stead. The median piperaillin concentrations reported below are derived from all measurements within the two weeks of treatment.
Time frame: Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pharmacokinetics Piperacillin 16g/Day | Blood-plasma Concentration of Piperacillin | 21 mg/L |
| Pharmacokinetics Piperacillin 12g/Day | Blood-plasma Concentration of Piperacillin | 21 mg/L |
Secondary
MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment.
MIC to piperacillin/tazobactam was obtained by using E-tests (AB Biodisk, Solna, Sweden) on Mueller-Hinton agar plates incubated at 35 ± 2 degrees Celcius with inoculum, incubation time and atmosphere in accordance to the E-test application guide.
Time frame: Sputum sample was collected 3 to 7 days before treatment initiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pharmacokinetics Piperacillin 16g/Day | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 3 mg/L |
| Pharmacokinetics Piperacillin 12g/Day | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 8 mg/L |
| T>MIC 16g/Day, Patient 3 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 16 mg/L |
| T>MIC 16g/Day, Patient 4 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 3 mg/L |
| T>MIC12g/Day, Patient 6 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 0.5 mg/L |
| T>MIC 12g/Day, Patient 7 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 3 mg/L |
| T>MIC 12g/Day, Patient 8 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 3 mg/L |
| T>MIC 12g/Day, Patient 9 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 0.75 mg/L |
| T>MIC 12g/Day, Patient 10 | MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment. | 2 mg/L |
Secondary
The Time Above the Minimum Inhibitory Concentration (T>MIC)
The time, expressed in percentage, for which the plasma concentration of Piperacillin lies above the minimum inhibitory concentration for the pathogen,during the treatment. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%. MIC for the pathogen in sputum was not reported in patient 5. Therefore,T\>MIC for this patient could not be estimated. Patient 1-5 were treated with piperacillin 16g/day. Patient 6-10 were treated with piperacillin 12g/day.
Time frame: Patients will be followed for the duration of treatment, which is approximately 2 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pharmacokinetics Piperacillin 16g/Day | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| Pharmacokinetics Piperacillin 12g/Day | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| T>MIC 16g/Day, Patient 3 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 75 % of time above the MIC |
| T>MIC 16g/Day, Patient 4 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 75 % of time above the MIC |
| T>MIC12g/Day, Patient 6 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| T>MIC 12g/Day, Patient 7 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| T>MIC 12g/Day, Patient 8 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| T>MIC 12g/Day, Patient 9 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |
| T>MIC 12g/Day, Patient 10 | The Time Above the Minimum Inhibitory Concentration (T>MIC) | 100 % of time above the MIC |