Efficacy and safety of a colistin loading dose, population pharmacokinetic-pharmacodynamic profiles and bacterial clearance rate in critically ill patients with extensively drug-resistant Acinetobacter baumanii (XDRAb) infections
In critically ill patients infected with extensively drug resistant Acinetobacter baumanii (XDRAb), does the use of colistin loading dose compared to the normal maintenance of colistin has better 30 day mortality outcome?
Helmi B Sulaiman
100 participants
Aug 15, 2013
Interventional
Conditions
Summary
We aim to evaluate prospectively the efficacy and safety of a colistin loading dose, to determine the population pharmacokinetic/pharmacodynamic (PK/PD) profiles and the effect of initial rate of bacterial clearance on in-hospital in patients with infections of the lungs, blood, or CSF, caused by extensively drug-resistant Acinetobacter baumanii (XDRAb). Objectives The objectives of this study include: 1. To determine, the effect of a loading dose and initial rate of bacterial clearance on 30-day mortality in patients with XDRAb infections 2. To assess the changes in renal function of patients receiving a loading dose of collision 3. To estimate the pharmacokinetic parameters (such as clearance and volume of distribution) and pharmacodynamic parameters (such as ratios of Cmax/MIC, AUC/MIC or T greater than MIC) of colistin in patients with XDRAb infections in critically ill patients. 4. To evaluate whether the initial rate of bacterial clearance can be used to predict mortality. Hypotheses to be investigated 1) A colistin loading dose is no superior to no loading in 30-day mortality in critically ill patients having infections caused by XDRAb. 2) A colistin loading dose is not associated with an increased risk of nephrotoxicity
Eligibility
Inclusion Criteria4
- Age 18 and above
- Patients with a first episode of culture proven XDRAb from blood, CSF, sputum and tracheal aspirate samples.
- Receive colistin treatment for more than 72 hours
- Fulfill diagnostic criteria for ventilator-related pneumonia, hospital-acquired pneumonia, bacteremia (catheter- and non catheter-related), and meningitis or CSF infections, as defined in accordance with IDSA guidelines
Exclusion Criteria4
- Pregnant
- Breastfeeding
- ALT/AST more than 8 times upper limit of normal
- Allergy to colistin or its prodrug
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
Colistin in this study will be given intravenously to all the patients. The loading dose of colistin will be used in selected patient who will be randomised using a computer generated block. Colistin is a parenteral drug in the form of prodrug called colistimethate sodium (CMS). The generic drug is named colomycin. We will use the Garonzik et. al. calculation method that was published in 2011, a study on colistin population PKPD. The maintenance will also be calculated using the formula from the paper that is dependent on the creatinine clearance. We will provide the physicians and the investigators with the study protocol to ensure that there will be a systemic and planned review of each participants. The loading dose is calculated based on weight in which the formula used will be, 2 x 2 x ideal body weight. The dose will be in colistin based activity (CBA) in which the loading dose is given irrespective of the creatinine clearance This loading dose will be given only once pre maintenance amongst subjects randomized into the the loading dose arm The maintenance as per the formula will be calculated based on creatinine clearance. We will use the online CKD EPI calculator for the calculation of creatinine clearance. The formula will be, 2 (1.5 x creatinine clearance + 30). The sum will be expressed in CBA too. The subjects will be maintained on the maintenance dose for at 10 to 14 days depending on the clinical response and the type of infections. The subjects will be followed up till 30 days post commencement of antibiotic or till he/she is discharged (whichever comes first)
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12613000862741