Can a Simple Stool Swab Predict Bacteremia in High-Risk Hematopoietic Cell Transplant Recipients?

(See the Major Article by Satlin et al on pages 1257–65.)

Hematopoietic cell transplant (HCT) recipients are at high risk for blood stream infections (BSI) due to chemotherapy-related mucositis, microbiome disruptions, immunosuppression, and the development of graft-versus-host disease (GVHD). Infections remain one of the most common causes of nonrelapse mortality among those undergoing allogeneic HCT [1]. To deal with such risks, transplant programs have modified regimens to limit toxicities, infection prevention has improved, and GVHD prevention has evolved, leading to declines the rate of gram-negative (GNR) BSI [2]. However, even in the modern era of improved outcomes, GNR BSI are associated with significant morbidity and mortality in this population [3].

For this reason, fluoroquinolone (FQ) prophylaxis has for years been the most frequently employed method to limit bacterial complications in the early pre-engraftment phase of HCT. There is also recognition that FQ use has downsides and limitations. The development of resistance is problematic [4], and despite lowering BSI, mortality benefits with FQ prophylaxis are debatable if present at all [5]. Although some within the transplant community are re-examining or have abandoned universal FQ prophylaxis entirely [6], most guidelines remain supportive of this approach.

The paper by Satlin and colleagues [7] demonstrates new findings that challenge the one-size-fits-all prophylactic dogma. In this observational study, HCT recipients on FQ prophylaxis had stool swabs collected on admission and weekly until neutropenia recovery to screen for FQ-resistant Enterobacteriaceae (FQRE). Nearly one quarter of patients were colonized with a FQRE pre-HCT; minority of patients acquired FQRE colonization post-HCT. Notably, post-transplant BSIs were significantly higher among FQRE colonized patients (31%) compared to those without evidence of gut colonization (1.1%). Using sequencing analyses, they found clear links between the development of FQRE BSI in 43% of patients colonized with FQRE. Importantly, there was no molecular evidence suggesting transmission of FQRE between patients.

The striking difference in bacteremia risk of FQRE colonized patients suggests a unique opportunity pretransplant for predicting and potentially preventing BSI post-HCT and questions the value of FQ prophylaxis in this group. For a long time many centers have screened for other resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) as a method to prevent transmission, but using screening as a tool to predict outcomes could shift our thinking when considering prophylaxis. In addition, the finding that FQRE colonizers were often resistant to other antibiotics suggests that screening could also modify how we empirically treat HCT recipients with neutropenic fever. Finally, screening could help to develop more targeted individual approaches for patients that could support antibiotic stewardship programs.

This work doesn’t help us understand predictors pre-HCT for FQRE colonization or the role of varied and often prolonged antibiotic exposures that patients receive prior to reaching HCT. Furthermore, it isn’t clear if these patients hadn’t received prophylaxis if outcomes would have been the same regardless. Unfortunately, the study does not address if FQ prophylaxis in FQRE colonized patients reduced gut microbiome diversity leading to FQRE dominance and thus higher risk for BSI with these resistant pathogens.

However, this study does again ask about the “elephant” in the room—should we continue to use FQ prophylaxis for patients with hematologic malignancies and/or HCT? Or more specifically, when do the risks of FQ prophylaxis outweigh the benefits? Although this study cannot definitively answer such questions, it suggests that individualized prophylaxis might be a future direction. Screening for FRQE could be the first stage toward the development of more patient-specific antibiotic plans and a pivot away from universal FQ prophylaxis especially in FQRE colonized patients. Such an approach focused on antibiotic precision could be a gargantuan step toward protecting these high-risk patients.

Notes

Potential conflicts of interest. S. A. P. receives grant/research support from Global Life Technologies, Inc. and has participated in research trials with Chimerix, Inc, and Merck & Co (paid to the institution). He has participated in a clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (U01-AI132004); vaccines for this trial were provided by Sanofi-Aventis. He has received payment/honoraria from Pall Medical None are involved in the development of this manuscript. S. S. D. receives research support from Merck, Allovir, KARIUS, Ansun Biopharma, Takeda/ Shire (paid to institution), and is on speaker’s bureau for/receives honoraria from Merck and Astellas. He is consultant for/receives consulting fees from Merck, Allovir, and Aseptiscope. He receives stock/stock options from Aseptiscope. None are involved in the development of this manuscript. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.