Recognizing and Overcoming Resistance to New Beta-Lactam/Beta-Lactamase Inhibitor Combinations

  • Stephanie Ho
  • Lynn Nguyen
  • Trang Trinh
  • Conan MacDougallEmail author
Antimicrobial Development and Drug Resistance (K Claeys and A Vega, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Antimicrobial Development and Drug Resistance


Purpose of Review

To describe the mechanisms and clinical relevance of emergent resistance to three recently introduced beta-lactamase inhibitor combinations (BLICs) active against resistant Gram-negative organisms: ceftolozane-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam.

Recent Findings

Despite their recent introduction into practice, clinical reports of resistance to BLICs among typically susceptible organisms have already emerged, in some cases associated with therapeutic failure. The resistance mechanisms vary by agent, including mutations in beta-lactamase active sites, upregulation of efflux pumps, and alterations in the structure or expression of porin channels. These changes may confer cross-resistance or, rarely, increased susceptibility to related agents. Clinicians need to be aware of the potential for initial or emergent resistance to BLICs and ensure appropriate antimicrobial susceptibility testing is performed. Dose optimization and novel combinations of agents may play a role in preventing and managing resistance.


Recently approved BLICs have provided important new therapeutic options against resistant Gram-negative organisms, but are already coming up against emergent resistance. Awareness of the potential for resistance, early detection, and dose optimization may be important in preserving the utility of these agents.


Antimicrobial resistance Ceftazidime-avibactam Ceftolozane-tazobactam Meropenem-vaborbactam Pseudomonas aeruginosa Carbapenem-resistant Enterobacteriaceae 


Compliance with Ethical Standards

Conflict of Interest

Stephanie Ho, Lynn Nguyen, and Trang Trinh declare no conflicts of interest.Conan MacDougall has received honoraria from Shionogi Pharmaceuticals and has served on an advisory board for Paratek Pharmaceuticals.

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 •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Stephanie Ho
    • 1
  • Lynn Nguyen
    • 2
  • Trang Trinh
    • 1
  • Conan MacDougall
    • 1
    Email author
  1. 1.University of California San Francisco School of PharmacySan FranciscoUSA
  2. 2.University of California San Francisco Medical CenterSan FranciscoUSA

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