Extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

Abstract

Background: Infections caused by multidrug-resistant gram-negative bacilli (MDR GNB), in particular extended-spectrum β-lactamase-producing (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), pose a major threat in solid organ transplantation (SOT). Outcome prediction and therapy are challenging due to the scarcity of randomized clinical trials (RCTs) or well-designed observational studies focused on this population.

Methods: Narrative review with a focus on the contributions provided by the ongoing multinational INCREMENT-SOT consortium (ClinicalTrials identifier NCT02852902) in the fields of epidemiology and clinical management.

Results: The Spanish Society of Transplantation (SET), the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC), and the Spanish Network for Research in Infectious Diseases (REIPI) recently published their recommendations for the management of MDR GNB infections in SOT recipients. We revisit the SET/GESITRA-SEIMC/REIPI document taking into consideration new evidence that emerged on the molecular epidemiology, prognostic stratification, and treatment of post-transplant ESBL-E and CRE infections. Results derived from the INCREMENT-SOT consortium may support the therapeutic approach to post-transplant bloodstream infection (BSI). The initiatives devoted to sparing the use of carbapenems in low-risk ESBL-E BSI or to repurposing existing non-β-lactam antibiotics for CRE in both non-transplant and transplant patients are reviewed, as well as the eventual positioning in the specific SOT setting of recently approved antibiotics.

Conclusion: Due to the clinical complexity and relative rarity of ESBL-E and CRE infections in SOT recipients, multinational cooperative efforts such as the INCREMENT-SOT Project should be encouraged. In addition, RCTs focused on post-transplant serious infection remain urgently needed.

Keywords: INCREMENT-SOT Project; antibiotics; carbapenem-resistant Enterobacterales; extended-spectrum β-lactamase-producing Enterobacterales; solid organ transplantation; treatment.