The mortality in patients with sepsis and severe acute kidney injury requiring continuous renal replacement therapy (CRRT) remains high. Antibiotic therapy is a key treatment of these patients and in recent years new antibiotics have been licensed. However, data is lacking to determine the optimal dosing regimens of these antibiotics for high (Australia and other countries) and low intensity (Japan) of CRRT. Aim To establish the appropriate dosing regimens of newly available antibiotics during CRRT can applied globally.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
120
Arterial blood samples will be collected just before the commencement of continuous venovenous haemofiltration (CVVHF) and 1 h after the termination of CVVHF. Prefilter and post-filter venous blood samples and filtered fluid will be collected 1 and 3 h after the commencement of CVVHF and at the end of CVVHF.
Plasma new antibiotics concentration during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.
New drugs are Tedizolid, Daptomycin (anti-MRSA), Tazobactam/ Ceftolozane (anti-gram negative), Metronidazole (Anti-anaerobic). Plasma antibiotics concentrations will be measured at 5 time-points and prefilter and postfilter plasma and filtered-fluid antibiotics levels will be measured at 3 time-points during CVVHF.
Time frame: 72 hours
Calculated clearances of new antibiotics during continuous venovenous haemofiltration (CVVHF) in critically ill patients receiving infusion of these drugs.
New drugs are Tedizolid, Daptomycin (anti-MRSA), Tazobactam/ Ceftolozane (anti-gram negative), Metronidazole (Anti-anaerobic). Total clearance by CVVHF: (Cltotal) = (Cpre - Cpost / Cpre) × Blood flow (ml/min), Clearance by filtration: (Clfil) = (Clfil / Cpre)× replacement volume (ml/min), Clearance by absorption of the filter: (Clab) = (Cltotal) - (Clfil) (ml/min).
Time frame: 72 hours
Concentration of serum creatinine
Concentration of serum creatinine
Time frame: through study completion, an average of 1 year
length of stay in the hospital
length of stay in the hospital
Time frame: up to 30 days, length of stay in the hospital will be calculated using the earliest of date that the subject is medically ready for discharge when captured, the date of discharge
ICU Mortality
Mortality at ICU discharge
Time frame: at ICU discharge assessed up to 30 days
Hospital Mortality
Mortality at hospital discharge
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Time frame: at hospital discharge assessed up to 30 days