Predicting and preventing antimicrobial resistance utilizing pharmacodynamics: part II Gram-negative bacteria

ABSTRACT

Introduction: Antimicrobial resistance is a serious health threat worldwide. Better understanding of exposure targets that could suppress resistance amplification is necessary to guide the dosing of currently available agents as well as new therapies in the drug development process.

Areas covered: This review will discuss studies that focused on predicting development of resistance using the pharmacokinetic-pharmacodynamic approach and how to design dosing regimens that can successfully suppress resistance emergence in Gram-negative bacteria.

Expert opinion: Pharmacokinetic-pharmacodynamic targets could provide useful insights to guide antimicrobial dosing to prevent resistance emergence. Exposure targets required for resistance suppression are higher than those for efficacy and might not be clinically feasible. Combination therapy is a possible approach to improve the efficacy and minimize the resistance emergence for difficult-to-treat infections.

KEYWORDS:

• Β-lactams
• fluoroquinolones
• MPC
• PK/PD
• polymyxins
• resistance

Article highlights

• Using pharmacokinetics and pharmacodynamics principles could help to design antimicrobial regimens that suppress emergence of resistance.

• Exposure targets to suppress resistance to fluoroquinolones among Gram-negative bacteria have been extensively investigated.

• %T>MPC might be a useful parameter for suppression of resistance to β-lactams.

• Current recommended doses of fluoroquinolones, β-lactams and polymyxins might not be sufficient to suppress resistance.

• Combination therapy might be a suitable approach to increase antimicrobial activity and minimize emergence of resistance.

This box summarizes key points contained in the article.

Declaration of interest

M Nailor has received research grants from Merck and has acted as consultant for Astellas. D Nicolau has been a speaker, received research grants and has consulted for Merck, Bayer, Pfizer and Cepheid. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded