Abstract: TH-PO120
AKI Is Not an Independent Risk Factor for Low Probability of Target Attainment (PTA) of Piperacillin
Session Information
- AKI: Biomarkers, Drugs, Onco-Nephrology
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Fissell, William Henry, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Evans, Rachel C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Verhoven, Sylvia M., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Creech, C. Buddy, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Vincz, Andrew J., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Patel, Pratish C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Shotwell, Matthew S., Vanderbilt University, Nashville, Tennessee, United States
Background
Infection is the leading cause of death in patients with acute kidney injury (AKI). Most antibiotics are renally cleared. Dose adjustments are based on imperfect estimates of renal function. We have shown that patients with severe AKI (e.g., continuous dialysis) are often underdosed. We hypothesize that piperacillin is underdosed in less severe AKI as well.
Methods
In a prospective study, patients admitted to the intensive care unit (ICU) had piperacillin concentrations measured in residual blood samples (RBS). Concentration-time curves for each patient were estimated from RBS values using nonlinear mixed-effects methods and a two-compartment model in NONMEM and R. AKI was assessed on each day of ICU admission based on modified KDIGO criteria. Patients were grouped according to the most severe AKI observed during their admission. Piperacillin PTA for patients with KDIGO classes 0,1,2, or 3 were estimated from concentration-time curves during the dosing period in which the first RBS was collected. PTA frequencies were compared using Pearson chi-square test. For this analysis, an MIC of 16μg/ml piperacillin was used, as it is the CLSI susceptibility breakpoint for clinical isolates of Enterobacteriaceae. PTZ was infused over 4 hours, per institutional protocol, to optimize pharmacodynamics.
Results
We measured piperacillin levels of 386 patients, of whom 86 were excluded due to incomplete data (74) or RRT for non-renal indications (12). Of the remaining patients, 113 met KDIGO 1-3 AKI criteria and 187 had no AKI. There were no significant differences in age, weight, or gender between groups. Most patients received 3.375 gm PTZ q8h; 28% of the AKI group received 3.375 gm q12h. 93% of the AKI group and 77% of the non-AKI group achieved a of fT>MIC > 50% (P < 0.001). These percentages decreased to 48% and 41% respectively for fT > MIC = 100% (P = 0.226).
Conclusion
ICU patients with AKI are not at increased risk of failing to achieve a commonly accepted PK target for piperacillin compared to patients without AKI. The biosample collection may not be synchronized to the AKI occurrence. However, given that fewer than 50% of critically ill patients attain a conservative target of ft > MIC = 100%, strategies to improve dosing and measure variation in exposure are urgently needed.
Funding
- Commercial Support – Baxter Healthcare