Abstract
Damage to gut mucosa following conditioning regimens may favour bacterial infections that can trigger graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Rifaximin, an oral and non-absorbable antibiotic, has been recently proposed as effective prophylaxis to reduce bacterial infections in the gut and consequently acute GvHD in this setting. The present study evaluated safety and outcomes of HSCT patients that were treated with rifaximin prophylaxis at Perugia University Hospital. Rifaximin prophylaxis was introduced as standard of care in HSCT patients in May 2018. We retrieved data from 118 consecutive transplants, and we compared the outcomes of rifaximin-treated patients with historical controls that did not receive antibiotic prophylaxis. While incidences of neutropenic fever, documented bacterial infections, and aGvHD were similar in the two groups, we found an increased frequency of invasive candidiasis and clinically relevant Candida spp. infections in rifaximin-treated patients (5 patients vs 1 patient, 25% [± 0.99%] vs 1% [± 0.01%], p < .0001). Three rifaximin-treated patients experienced life-threating candidemia (2 C. krusei, 1 C. orthopsilosis). Rifaximin was the only factor that increased the risk of Candida spp. infections. Rifaximin could have contributed to microbiome disruption which favoured an outbreak of life-threatening Candida infections. This important complication forced us to halt its use. Larger, prospective studies are needed to assess the impact of rifaximin prophylaxis on incidence of bacterial infections, aGvHD, and survival of HSCT patients.
Highlights
Bacterial infections are common complications during neutropenia that follows allogeneic hematopoietic stem cell transplantation (HSCT), but there is no general consensusOn November 19th, 2020, the study was registered at the local (Umbria Italian region) ethical committee (IRB) with registration number 01/2020 in CER (Comitato Etico Regionale) registry (N.: 3865/19).Recent studies show that intestinal microbiota regulates immune homeostasis
The present study shows rifaximin prophylaxis could favour Candida spp. infections in patients who undergo allogeneic HSCT and are treated with echinocandin-based antifungal prophylaxis
The low number of patients that were treated with rifaximin prophylaxis at our institution does not allow us to evaluate its efficacy in preventing bacterial infections and, its possible impact on incidence of acute graft-versus-host disease (aGvHD)
Summary
Bacterial infections are common complications during neutropenia that follows allogeneic hematopoietic stem cell transplantation (HSCT), but there is no general consensusOn November 19th, 2020, the study was registered at the local (Umbria Italian region) ethical committee (IRB) with registration number 01/2020 in CER (Comitato Etico Regionale) registry (N.: 3865/19).Recent studies show that intestinal microbiota regulates immune homeostasis. Loss of microbiota diversity and prevalence of enterococci have been linked to the onset of acute graft-versus-host disease (aGvHD), an immune-mediated and potentially life-threatening complication of HSCT [4, 5]. A. Annals of Hematology (2021) 100:2375–2380 single-centre retrospective study by Weber et al suggested that antibiotic prophylaxis with rifaximin could reduce incidence of aGvHD and improve overall survival of transplanted patients if compared to fluoroquinolone plus metronidazole prophylaxis [6]. Our group historically chose to avoid antibiotic prophylaxis for HSCT patients because of high prevalence of fluoroquinolone-resistant bacterial infections. Following the study by Weber et al, we recently changed this policy and introduced antibiotic prophylaxis with rifaximin to reduce such infections and, possibly, incidence of aGvHD. We report incidence of infections and outcomes of patients that received rifaximin prophylaxis at our institution
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