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Abstract: SA-PO254

Piperacillin/Tazobactam Dosing Recommendation in Critically Ill Patients Receiving Tablo Kidney Replacement Therapy

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Lewis, Susan J., University of Findlay, Findlay, Ohio, United States
  • Mueller, Bruce A., University of Michigan, Ann Arbor, Michigan, United States
Background

Tablo kidney replacement therapy (KRT) machines provide flexibility in treatment duration, frequency, and effluent rates to treat ICU patients with AKI. These KRT options may clear piperacillin/tazobactam (PIP/TAZ) differently than conventional KRTs. This study’s purpose was to predict PIP/TAZ doses likely to attain the efficacy targets in critically ill patients receiving Tablo KRT, using Monte Carlo simulation (MCS).

Methods

Pharmacokinetic models were developed using pertinent demographic & pharmacokinetic parameters to predict PIP/TAZ exposure in 5,000 virtual, anuric patients receiving 5 different KRT regimens (Table 1). PIP/TAZ doses with 0.5 or 4 hour infusions were simulated to assess the probability of target attainment (PTA). The 3 PIP efficacy targets used were 1) free plasma concentrations above the MIC for ≥50% of the dosing interval (≥50% fT>MIC), 2) free concentrations for ≥50% of the dosing interval ≥4 times above the MIC (≥50% fT >4xMIC), or 3) 100% fT >MIC. Breakpoint MIC used was 16 mg/L for P. aeruginosa. TAZ target was ≥50% fT> threshold concentration of 4 mg/L. The toxicity risk of each PIP dose was predicted with using a safety threshold (157 mg/L). The smallest doses attaining PTA≥90% during 1-week of therapy were considered optimal.

Results

PIP/TAZ doses attaining the different efficacy targets in the 5 KRT settings are shown in Table.

Conclusion

MCS predicted the same PIP/TAZ doses for 3x/wk HD, daily HD, sequential HD/UF, and PIKRT while higher doses are necessitated for extended therapy. Higher doses were required for aggressive efficacy targets, but these were likely to increase the toxicity risk. These findings need clinical validation.

Funding

  • Commercial Support – Outset Medical