Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: a multicenter case-control study in China

Objective: To investigate clinical characteristics of hematological malignancy (HM) patients with carbapenem-resistant gram-negative organism (CRO) bloodstream infections (BSI) in China, and to elucidate the prognostic risk factors of CRO BSI.

Methods: We conducted a multicenter case-control study of 201 HM patients with CRO BSI between 2018-2020. Antimicrobial susceptibility testing and whole genome sequencing were performed for CRO isolates. Independent risk factors for 28-day crude mortality of were analyzed using Cox proportional hazards regression models. The subgroups of major species were also evaluated.

Results: The pathogens responsible for CRO BSI in HM patients dominated by ST11 CRKP, ST167 CREC and ST463 CRPA. Most isolates produced carbapenemases with KPC and NDM being the main. CRO isolates had resistance rates to conventional antimicrobials ranging from 55%-100% and poor susceptibility to novel antimicrobials related to carbapenemases and species. The 28-day crude mortality was 24.2%. Non-Hodgkin lymphoma, heart disease, bla_KPC-2 positive, empirical antibiotic therapy with linezolid, Pitt bacteremia score >3.5 were risk factors for 28-day mortality and appropriate definitive antibiotic therapy, tigecycline-containing therapy and aminoglycoside-containing therapy were protective factors. bla_KPC-2 positive in CRKP and ST463 in CRPA were associated with Pitt bacteremia score > 3.5. Solid tumor and other site infections before BSI were risk factors for ST463 CRPA BSI and Pulmonary infection before BSI was risk factor for KPC-KP BSI.

Conclusions: The antimicrobial resistance of CRO isolates for BSI in HM patients is critical. HM patients with CRO BSI should be treated with appropriate definitive antibiotic therapy based on early clarification of pathology and their antimicrobial susceptibility.