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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically

Thomas P Lodise1, Scott Van Wart2, Zoe M Sund3

  • 1Albany College of Pharmacy and Health Sciences, Albany, New York, USA Thomas.Lodise@acphs.edu.

Antimicrobial Agents and Chemotherapy
|November 10, 2020
PubMed

Insights

Intravenous minocycline dosing may be suboptimal for treating multidrug-resistant Acinetobacter baumannii infections. This study found current regimens may not achieve pharmacokinetic-pharmacodynamic targets, suggesting a need for clinical confirmation and potential dose adjustments.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Intravenous (i.v.) minocycline is increasingly used for multidrug-resistant (MDR) Acinetobacter baumannii infections.
  • Limited published data exist on the pharmacokinetic (PK) profile of i.v. minocycline.
  • Understanding PK and pharmacokinetic-pharmacodynamic (PK-PD) targets is crucial for optimizing antimicrobial therapy.

Purpose of the Study:

  • To examine the PK profile of i.v. minocycline in critically ill patients.
  • To evaluate the probability of PK-PD target attainment for i.v. minocycline against Gram-negative bacteria.
  • To assess the PK-PD targets associated with stasis and 1-log killing in an animal model of A. baumannii pneumonia.

Main Methods:

  • A multicenter study involving 55 critically ill patients receiving a single 200-mg i.v. dose of minocycline.
  • Plasma samples were collected at multiple time points to determine total and unbound minocycline concentrations.
  • A two-compartment population PK model was developed, incorporating body surface area and albumin as covariates.

Main Results:

  • The PK data were best characterized by a two-compartment model with body surface area and albumin influencing distribution and unbound fraction.
  • Minocycline 200 mg i.v. every 12 hours (Q12H) was predicted to yield suboptimal PK-PD target attainment for A. baumannii infections with MIC >1 mg/liter.
  • The free area under the curve above the minimum inhibitory concentration (fAUC:MIC) targets of 12 (stasis) and 18 (1-log killing) were evaluated.

Conclusions:

  • Current i.v. minocycline dosing regimens (200 mg Q12H) may be suboptimal for treating A. baumannii infections, particularly with elevated MICs.
  • The study highlights the need for clinical validation of these PK-PD findings.
  • Further research may be warranted to optimize minocycline dosing strategies in critically ill patients with MDR Gram-negative infections.
Keywords:
Acinetobacterminocyclinepharmacodynamicspharmacokineticspopulation pharmacokinetics

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