Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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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
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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).

Official Title
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Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pharmacokinetics Piperacillin<br>Patients with cystic fibrosis , treated with Piperacillin/Tazobactam, given as continuous infusion for a period of two weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Patients will be followed for the duration of treatment, which is approximately 2 weeks. | 
| 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. | Sputum sample was collected 3 to 7 days before treatment initiation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Continuous infusion, Pharmacokinetics