Pharmacokinetics of Colistin in Critically-ill Patients With AKI Who Receive SLED
Condition: Bacterial Infections
MeSH terms: Bacterial Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      Colistin was developed in the 1960s and preliminary pharmacokinetic studies were performed at
      that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed
      in the drug's product information. However, there are no optimal dosing recommendations for
      patients with acute kidney injury who receive sustained low-efficiency dialysis. Furthermore,
      the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the
      1960s and it is quite possible that the dosing recommendations listed in the product
      information are not optimal. Furthermore, even though physicians refer to "colistin"
      administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS
      is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic
      and antimicrobial activities. For this reason, we, the investigators at the Mahidol
      university, are performing a pharmacokinetic study of the intravenous CMS/colistin in
      patients requiring sustained low-efficiency dialysis. Plasma concentrations will be
      determined around a CMS/colistin dose once the drug has reached steady state. Microbiologic
      and clinical endpoints will be determined and will be correlated with these concentrations.
      The measurement of CMS and colistin levels will be determined by a laboratory in Australia.
    

Detailed description: 
      At baseline (upon signing informed consent), the following information will be collected:
      Demographic data - age, sex, height, weight, state of birth, underlying illnesses, underlying
      infection, immunosuppression, antibiotic use, laboratory results, current medication use, any
      other prior medical problems/history and clinical outcomes.

      The research coordinator will contact the patient on days 14, 28 and 90 days after the
      infection to determine clinical outcome. If the patient is still an inpatient the research
      coordinator will visit the patient in their hospital room to evaluate the patient's health
      status. This visit will take about 10 minutes. If the patient has been discharged from the
      hospital, the patient will be contacted by telephone by the research coordinator to determine
      the health status, if no recent electronic medical record exists. This telephone contact will
      take about 10 minutes.

      Blood work and microbiologic samples to be collected:

      Collection of ten samples of 4 mL blood each day during two days of colistin treatment (the
      dialysis day and non-dialysis day) of colistin therapy will occur. These samples will be
      collected:

      immediately pre-dose, at the end of the colistin infusion, 60 minutes after the end of the
      colistin infusion, 2 hours after the end of the colistin infusion, 5 hours after the end of
      the colistin infusion, 8 hours after the end of the colistin infusion, 12 hours after the end
      of the colistin infusion (or immediately prior to the next dose if the drug is being given
      every 12 hours).

      13 hours after the end of the colistin infusion, 16 hours after the end of the colistin
      infusion, 20 hours after the end of the colistin infusion, 24 hours after the end of the
      colistin infusion, Indwelling venous and arterial access lines, if already in place, will be
      utilized for the pharmacological study's blood draws.

      On dialysis day, collection of dialysate fluid will also occur.

      60 minutes after the end of the colistin infusion, 3 hours after the end of the colistin
      infusion, 5 hours after the end of the colistin infusion, 7 hours after the end of the
      colistin infusion

      Rationale: The samples will be utilized for quantification of plasma levels of colistin.

      Collection of microbiologic samples within 48-96 hours of the initiation of colistin therapy.
      These samples are two sets of blood cultures if the patient had bacteremia, a sputum culture
      if the patient had pneumonia.

      Rationale: These samples will be used to determine if there has been rapid bacteriologic
      clearance of infection.

      The blood samples will be processed and stored in a -80° C freezer in a secured laboratory
      under the supervision of the principal investigator. These samples will then be sent to the
      laboratory of Drs Jian Li and Roger Nation in Melbourne, Australia, to determine the amount
      of colistin and CMS that reached the participant's blood following dose administration. All
      samples will be sent de-identified.

      All samples will be analyzed to obtain the amount of colistin and CMS found in the blood. The
      biologic samples will be under the control of the principal investigator of this research
      project. To protect confidentiality, all personal identifiers (i.e., name, social security
      number, and birth date) will be removed (de-identified) and replaced with a specific code
      number. The information linking these code numbers to the corresponding subjects' identities
      will be kept in a separate, secure location.

      Other items to be collected for study purposes:

      An unopened vial of colistin from the same batch as used for the patient will be collected
      for analysis, so the actual dose of colistin can be calculated.
    

Intervention name(s): Colistin Sulfomethate
Intervention type(s): Drug
Intervention description(s): The patients receive colistin 150 mg intravenous once daily on non-dialysis day and receive colistin 150 mg intravenous every 12 hours on dialysis day
Other intervention name(s): Colistin
Intervention MeSH terms: Colistin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: colistin