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

Abstract

Background. The clinical outcomes associated with, and risk factors for, carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) in solid organ transplant (SOT) recipients remain ill-defined. Methods. A multicenter retrospective cohort study was performed, including SOT recipients with an Enterobacterales BSI between 2005 and 2018. Exposed subjects were those with a CRE BSI. Unexposed subjects were those with a non-CRE BSI. A multivariable survival analysis was performed to determine the association between CRE BSI and risk of all-cause mortality within 60 d. Multivariable logistic regression analysis was performed to determine independent risk factors for CRE BSI. Results. Of 897 cases of Enterobacterales BSI in SOT recipients, 70 (8%) were due to CRE. On multivariable analysis, CRE BSI was associated with a significantly increased hazard of all-cause mortality (adjusted hazard ratio, 2.85; 95% confidence interval [CI], 1.68-4.84; P < 0.001). Independent risk factors for CRE BSI included prior CRE colonization or infection (adjusted odds ratio [aOR] 9.86; 95% CI, 4.88-19.93; P < 0.001)‚ liver transplantation (aOR, 2.64; 95% CI, 1.23-5.65; P = 0.012)‚ lung transplantation (aOR, 3.76; 95% CI, 1.40-10.09; P = 0.009)‚ and exposure to a third-generation cephalosporin (aOR, 2.21; 95% CI, 1.17-4.17; P = 0.015) or carbapenem (aOR, 2.80; 95% CI, 1.54-5.10; P = 0.001) in the prior 6 months. Conclusions. CRE BSI is associated with significantly worse outcomes than more antibiotic-susceptible Enterobacterales BSI in SOT recipients.

Clinical Outcomes and Risk Factors for Death following Carbapenem-Resistant Klebsiella pneumoniae Infection in Solid Organ Transplant Recipients

“…Patients with septic shock often present with massive proinflammatory cytokine-driven hyperinflammatory at the early phase; hence, intense levels of immunosuppression during the early post-transplant phase could limit excessive inflammation and protect these patients from entering an overwhelming hyperinflammatory phase, which substantially prevents disease progression and improves sepsis mortality ( 33 , 34 ). Another possible explanation is the fact that allograft function declines progressively over time ( 35 , 36 ), which is one important independent factor for death after infection ( 37 ). We found that 28.6% of infections (4 of 14) occurred in the 4- to 12-year period after transplant; therefore, it is possible that chronic allograft damage associated with the late post-transplant period could be attributed to the high mortality rate ( 37 ).…”

“…Another possible explanation is the fact that allograft function declines progressively over time ( 35 , 36 ), which is one important independent factor for death after infection ( 37 ). We found that 28.6% of infections (4 of 14) occurred in the 4- to 12-year period after transplant; therefore, it is possible that chronic allograft damage associated with the late post-transplant period could be attributed to the high mortality rate ( 37 ). This hypothesis is supported by our finding that we observed a trend toward high mortality in kidney transplant (47.6%) compared with lung transplant (35.0%) or liver transplant (35.8%).…”

Bloodstream infections after solid organ transplantation: clinical epidemiology and antimicrobial resistance (2016–21)

“… 28 , 29 CRE specifically made up 6.2% of all isolates and 12.9% of Enterobacterales, similar to proportions reported in a recent multicentre study. 30 The fact that kidney transplant recipients had a higher proportion of Enterobacterales (60.9%) than liver transplant recipients (36.1%) but no CRE may further reflect the selective pressure from peri-operative critical illness (and associated antibiotic exposure) among liver transplant patients. Interestingly, although CRE infection has been linked to high mortality, 30 , 31 there were no deaths among patients with CRE BSIs in our cohort.…”

“… 30 The fact that kidney transplant recipients had a higher proportion of Enterobacterales (60.9%) than liver transplant recipients (36.1%) but no CRE may further reflect the selective pressure from peri-operative critical illness (and associated antibiotic exposure) among liver transplant patients. Interestingly, although CRE infection has been linked to high mortality, 30 , 31 there were no deaths among patients with CRE BSIs in our cohort. Whether novel β-lactam/β-lactamase inhibitor combinations, which were introduced during our study period, may have contributed to this low mortality deserves further study.…”

The intricate interplay of immunosuppression and outcomes following Gram‐negative bloodstream infection in solid organ transplantation

“…The final observation of note from this study is that within the SOT population with GNB BSI, the number of immunosuppressants was inversely related to outcomes, in that the hazard of death decreased among those on three or more immunosuppressants as compared to those on one or fewer immunosuppressants. The authors postulate that this is due to a more controlled immune response to the GNB BSI, but there are other potential explanations as well, including (1) being on ≤1 immunosuppressant may be a marker of graft failure prior to the GNB BSI, which is a known risk factor for poor outcomes following GNB BSI 9 ; (2) those SOT recipients on ≥3 immunosuppressants may be a group who have had fewer prior infectious complications, since immunosuppression is often reduced in the setting of infection, and thus the higher number of immunosuppressants may be a marker of a less complicated posttransplant course; (3) as highlighted by the authors, the number of immunosuppressants is not a comprehensive measure of type or depth of immunosuppression, so may not be measuring the association that was intended. Thus, while it is a compelling finding, further study will be needed to better delineate the relationship between immunosuppression and outcomes with bacterial BSI.…”