Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant.

Abstract

Importance:

Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).

Objective:

To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.

Design, Setting, and Participants:

A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16 875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11 768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018.

Main Outcomes and Measures:

Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.

Results:

Of the 16 875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13 686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]).

Conclusions and Relevance:

In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population.

• Authors: Christopher E Dandoy, Soyoung Kim, Min Chen, Kwang Woo Ahn, Monica I Ardura, Valerie Brown, Saurabh Chhabra, Miguel Angel Diaz, Christopher Dvorak, Nosha Farhadfar, Aron Flagg, Siddartha Ganguly, Gregory A Hale, Shahrukh K Hashmi, Peiman Hematti, Rodrigo Martino, Taiga Nishihori, Roomi Nusrat, Richard F Olsson, Seth J Rotz, Anthony D Sung, Miguel-Angel Perales, Caroline A Lindemans, Krishna V Komanduri, Marcie L Riches
• Journal: JAMA network open (JAMA Netw Open) Vol. 3 Issue 1 Pg. e1918668 (01 03 2020) ISSN: 2574-3805 [Electronic] United States
• PMID: 31913492 (Publication Type: Journal Article)

Topics

• Adult
• Bacteremia (blood, epidemiology)
• Catheter-Related Infections (epidemiology, microbiology)
• Cross Infection (epidemiology, microbiology)
• Female
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Incidence
• Male
• Middle Aged
• Mucous Membrane (injuries, microbiology)
• Retrospective Studies
• Risk Factors