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Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles

  • Olivia Smibert
  • Michael J. Satlin
  • Anoma Nellore
  • Anton Y. PelegEmail author
Transplant and Oncology (M Ison, N Theodoropoulos and S Pergam, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Transplant and Oncology

Abstract

Purpose of Review

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.

Recent Findings

CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future.

Summary

As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.

Keywords

CRE CPE Transplant Treatment Gram-negative bacteria 

Notes

Acknowledgements

Anton Y. Peleg acknowledges support from an Australian National Health and Medical Research Council Practitioner Fellowship.

Compliance with Ethical Standards

Conflict of Interest

Olivia Smibert and Anoma Nellore declare that they have no conflict of interest.

Michael Satlin consulted for Shionogi and Achaogen and has received grant funding from Allergan and Merck. Anton Peleg has received research grant support through the investigator initiated research grant program from MSD.

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.

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Copyright information

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

Authors and Affiliations

  • Olivia Smibert
    • 1
    • 2
  • Michael J. Satlin
    • 3
  • Anoma Nellore
    • 4
  • Anton Y. Peleg
    • 1
    • 5
    Email author
  1. 1.Department of Infectious Diseases, The Alfred Hospital and Central Clinical SchoolMonash UniversityMelbourneAustralia
  2. 2.Transplant Infectious Disease and Compromised Host ProgramMassachusetts General HospitalBostonUSA
  3. 3.Division of Infectious DiseasesWeill Cornell MedicineNew YorkUSA
  4. 4.Division of Infectious DiseasesUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of MicrobiologyMonash UniversityClaytonAustralia

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