Polymicrobial bloodstream infection caused by three carbapenemase-producing Enterobacterales species in a neutropenic cancer patient: Clinical and genomic characterization.

Carbapenemase-producing Enterobacterales (CPE) represent a major global health threat due to limited therapeutic options and high mortality. While isolates harboring a single carbapenemase are increasingly common, polymicrobial bloodstream infections involving multiple carbapenemase-producing species remain rare and pose substantial diagnostic and therapeutic challenges. We describe a case of polymicrobial bloodstream infection in a neutropenic patient with relapsed acute myeloid leukemia. Blood cultures yielded three distinct Enterobacterales species. Identification was performed by MALDI-TOF MS, antimicrobial susceptibility testing followed CLSI guidelines, and carbapenemase production was screened by immunochromatographic assay and PCR. Whole-genome sequencing was conducted for all isolates, with in silico multilocus sequence typing, resistome characterization, plasmid replicon analysis, and phylogenetic reconstruction. A literature review (2015-2025) was performed to contextualize this finding. Three carbapenem-resistant Enterobacterales were simultaneously isolated from blood cultures: Citrobacter freundii producing NDM-1, Klebsiella michiganensis producing IMP-16, and Enterobacter hormaechei producing KPC-2. One isolate harbored mcr-9 gene. The patient developed septic shock but was successfully treated with a targeted combination therapy of ceftazidime-avibactam plus aztreonam, supplemented with amikacin, alongside catheter removal and supportive care. Follow-up blood cultures were negative, and no secondary transmission was detected. We report a case of a polymicrobial bloodstream infection caused by three different carbapenemase-producing Enterobacterales species, each expressing a distinct carbapenemase. This case underscores the clinical value of rapid molecular diagnostics, highlights the need for strengthened surveillance and tailored antimicrobial strategies in high-risk patients facing extreme antimicrobial resistance scenarios.