Pharmacokinetic and Pharmacodynamic Considerations of Antibiotics of Last Resort in Treating Gram-Negative Infections in Adult Critically Ill Patients

  • Mojdeh S. Heavner
  • Kimberly C. Claeys
  • Anne M. Masich
  • Jeffrey P. Gonzales
Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Healthcare Associated Infections


Purpose of Review

We provide an overview of antimicrobials that are considered last resort for the treatment of resistant gram-negative infections in adult critically ill patients. The role in therapy, pharmacodynamic (PD) goals, and pharmacokinetic (PK) changes in critical illness for aminoglycosides, polymyxins, tigecycline, fosfomycin, and fluoroquinolones are summarized.

Recent Findings

Altered PK in septic patients in the intensive care unit (ICU) is observed with many of our agents of last resort. Based on the available literature, dosage adjustments may be required to optimize PK parameters and meet PD targets for most effective bacterial killing. Data is limited, studies are conducted in heterogeneous patient populations, and conclusions are frequently conflicting. Strategic dosing regimens such as high-dose extended interval dosing of aminoglycosides or loading doses with colistin and polymyxin B are examples of ways to optimize antibiotic PK in critically ill patients. Benefits of these strategies must be balanced with risks of increased toxicity.


Patients with resistant gram-negative infections may present with septic shock in the ICU. Sepsis can significantly alter the PK of antibiotics and require dosage adjustments to attain optimal drug levels. An understanding of PK and PD properties of these agents of last resort will help to maximize therapeutic efficacy while minimizing toxic effects.


Aminoglycosides Polymyxins Tigecycline Fosfomycin Fluoroquinolones ICU 


Compliance with Ethical Standards

Conflict of Interest

Anne M. Masich, Mojdeh S. Heavner, Jeffrey P. Gonzales, and Kimberly C. Claeys declare they have no conflicts of interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mojdeh S. Heavner
    • 1
  • Kimberly C. Claeys
    • 1
  • Anne M. Masich
    • 1
  • Jeffrey P. Gonzales
    • 1
  1. 1.Department of Pharmacy Practice and ScienceUniversity of Maryland School of PharmacyBaltimoreUSA

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