Colonization with extended-spectrum and AmpC β-lactamase-producing Enterobacterales and bacteremia risk in patients with acute leukemia who receive induction chemotherapy without fluoroquinolone prophylaxis

ABSTRACT Neutropenic patients colonized with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) frequently develop ESBL-E bacteremia while receiving fluoroquinolone prophylaxis. However, the impact of colonization with ESBL-E and AmpC β-lactamase-producing Enterobacterales (AmpC-E) in neutropenic patients who do not receive fluoroquinolone prophylaxis is unclear. To investigate this, we conducted a prospective study of patients with acute leukemia or myelodysplastic syndrome (MDS) receiving induction chemotherapy without antibacterial prophylaxis between November 2015 and January 2020. Stool or perianal swab specimens were collected from study participants within 5 days of initiating chemotherapy and underwent culture for ESBL-E and AmpC-E. Isolated organisms were identified and subjected to antimicrobial susceptibility testing and whole-genome sequencing. Bacteremia risk during neutropenia was compared between ESBL-E-colonized, AmpC-E-colonized, and non-colonized patients. We enrolled 159 patients, of whom 15 (9%) were colonized with ESBL-E and 17 (11%) with AmpC-E. Fourteen (93%) of 15 colonizing ESBL-E isolates were cefepime resistant, compared to 2 (12%) of 17 AmpC-E isolates. Three (20%) of 15 ESBL-E-colonized patients developed ESBL-E bacteremia (colonizing and bloodstream isolates were genetically identical for each patient), compared to 1 (1%) of 144 patients without ESBL-E colonization ( P = 0.001). ESBL-E-colonized patients were also more likely to develop bacteremia due to ceftriaxone-susceptible Enterobacterales than non-colonized patients. AmpC-E-colonized patients did not have an increased risk of gram-negative bacteremia. In patients with acute leukemia or MDS who receive induction chemotherapy without fluoroquinolone prophylaxis, ESBL-E colonization is associated with increased risk of gram-negative bacteremia due to ESBL-E and ceftriaxone-susceptible organisms. Screening for ESBL-E colonization in this population could optimize empirical antibacterial therapy.