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Mid-dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill

Jing Wang1, Yuanchen Li2, Siqi Huang3

  • 1Department of Pharmacy, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

CPT: Pharmacometrics & Systems Pharmacology
|September 1, 2023
PubMed

Insights

White blood cell count and polymyxin B (PMB) exposure, measured by area under the concentration-time curve (AUC), are key risk factors for acute kidney injury (AKI) in critically ill patients. Therapeutic drug monitoring can guide PMB dosing.

Area of Science:

  • Pharmacology
  • Nephrology
  • Critical Care Medicine

Background:

  • Polymyxin B (PMB) is crucial for treating multidrug-resistant Gram-negative infections.
  • Acute kidney injury (AKI) is a significant complication associated with PMB therapy.
  • Identifying risk factors for PMB-induced AKI is essential for patient safety.

Purpose of the Study:

  • To investigate the association between PMB exposure and AKI in critically ill patients.
  • To identify independent risk factors contributing to PMB-induced AKI.
  • To establish predictive thresholds for AKI risk.

Main Methods:

  • Plasma PMB concentrations were measured using ultra-performance liquid chromatography-tandem mass spectrometry.
  • Univariate and multivariate analyses identified risk factors for AKI.
  • Receiver operating characteristic (ROC) curve analysis determined the predictive power and cutoff values.

Main Results:

  • White blood cell count and estimated area under the concentration-time curve (AUC) of PMB were independent risk factors for AKI.
  • The final predictive model achieved an area under the ROC curve of 0.805.
  • A C1/2t threshold of 3.47 μg/ml demonstrated favorable differentiation for AKI risk.

Conclusions:

  • White blood cell count and PMB AUC are significant predictors of AKI in critically ill patients.
  • Therapeutic drug monitoring of PMB, particularly C1/2t, can aid in optimizing dosing and mitigating AKI risk.
  • These findings support the clinical implementation of PMB therapeutic drug monitoring to improve patient outcomes.

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