Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P = .262) in auto-HSCT and 50% versus 43% (P = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P = .405) in auto-HSCT and 31% versus 25% (P = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P = .142) in auto-HSCT and 23% versus 14% (P = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P < .001) and increased TRM (P < .001) and IRM (P < .001). During the first year after transplant, we collected 73 GNB bloodstream infectious (BSI) episodes in 54 patients, 42.4% of which sustained by a MDR-GNB. Rectal swabs positivity associated with the pathogen causing subsequent MDR-GNB BSI episodes in 13 of 31 (41.9%). Overall, OS at 4 months from MDR-GNB BSI episode onset was of 67.9%, with a 14-day attributed mortality of 12.9%, not being significantly different between carriers and noncarriers (P = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is started in case of neutropenic fever.

Impact of Preemptive Granulocyte Infusions During Febrile Neutropenia in Patients Colonized with Carbapenem-Resistant Gram-Negative Bacteria Undergoing Haploidentical Transplantation

“…The same has been highlighted in a multicenter study in non-HCT patients from New York as well, which is supposed to be the CRGNB epicenter of the United States [31]. Even though some studies have claimed success of early initiation of CRGNB-directed antibiotics [26], our experience has not been gratifying with a similar approach. This was primarily because the GNB species responsible for colonization and BSI were often sensitive to colistin alone or even pan-resistant.…”

The relationship between mortality and microbiological parameters in febrile neutropenic patients with hematological malignancies

“… 3 - 5 , 7 But we found that Gram-negative bacteria was the most frequent microorganisms and these data are consistent with the recently reported shift of prevalence from Gram-positive to Gram-negative bacteria in neutropenic patients malignancy. 1 , 2 , 11 Endogenous flora that contains mainly of enterobacteriaceae in the gastrointestinal tract can cause bacteremia episodes in patients with neutropenia due to a breakdown of mucosal barriers secondary to chemotherapy. 19 The reduction in the use of the central venous catheter and the reduced presence of severe mucositis may have contributed to a decreasing in Gram-positive bacteremia.…”

“…Nowadays, the development of intensive chemotherapy protocols and interventional procedures have resulted a serious increase in cure rates of the patients, while immunosuppression caused by these treatments also enhances incidence rates of infection. 1 , 2 The relationship between fever and infection in neutropenic patients was defined during the 1960s. Initially, this rarely encountered relationship was described as a serious clinical entity after more widespread and intensive use of cytotoxic drugs and its treatment was started thanks to developed guidelines.…”

Multidrug‐resistant bacterial infections in children undergoing haematopoietic stem cell transplantation over a 6‐year period: analysis of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation

“…Across the haematology and oncology population, especially in the transplanted patients, MDR infections has been linked to increased intensive care unit requirements and mortality (Haeusler and Levene ). Although previous studies suggest an important role of MDR Gram‐positive bacteria, such as VRE or MRS in transplant recipients, their incidence in our cohort was lower, making the scenario as largely being dominated by Gram‐negative pathogens and thus becoming the main focus of our study (Scheich et al ; Forcina et al ).…”