Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles

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-totreat and highly morbid infections in transplant recipients.

Dissemination of Carbapenemases (OXA-48, NDM and VIM) Producing Enterobacteriaceae Isolated from the Mohamed VI University Hospital in Marrakech, Morocco

“…Over the past few years, carbapenem-resistant Enterobacteriaceae (CRE), the most frequent pathogens responsible for nosocomial infections, have emerged and rapidly spread all over the world, posing great challenges to human health [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Conventionally, carbapenem antibiotics have been considered the most effective among available antibacterial agents for the treatment of infections caused by Enterobacteriaceae (e.g., E. coli and Klebsiella pneumoniae ), and are still being used as the antibiotics of last-resort to date [ 8 , 9 ].…”

A Review on Bacterial Resistance to Carbapenems: epidemiology, Detection and Treatment Options

“…Novel β-lactamase inhibitors, such as vaborbactam, avibactam and relebactam, are capable of counteracting the effect of KPC and ESBLs [128]. Lately, new β-lactam/β-lactamase inhibitor combinations, namely meropenem/vaborbactam, ceftazidime/avibactam and imipenem/cilastatin/relebactam were approved by the US FDA (MD, USA) for the treatment of infections caused by CRE [118,129,130].…”

Clinical Outcomes and Risk Factors for Carbapenem-resistant Enterobacterales Bloodstream Infection in Solid Organ Transplant Recipients

“…[6][7][8] This is likely driven by SOT recipients' multicomorbidity, frequent healthcare and antibiotic exposures, frequent procedures, and chronic indwelling medical devices. [9][10][11][12] Notably, however, several studies have identified transplant status as an independent risk factor for CRE infection, even after adjusting for other risk factors, 7 suggesting there may be issues unique to transplantation that increase the risk for CRE infection. 12 Furthermore, prior studies have indicated that outcomes following CRE infection in SOT recipients are poor, with rates of graft failure and death ranging between 12% and 66%, depending on the transplant cohort, the type of CRE infection studied, and the duration of follow-up.…”