Rifaximin use favoured micafungin-resistant Candida spp. infections in recipients of allogeneic hematopoietic cell transplantation

Ann Hematol. 2021 Sep;100(9):2375-2380. doi: 10.1007/s00277-021-04569-x. Epub 2021 Jun 28.

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.

Keywords: Candida; Echinocandin; Hematopoietic stem cell transplantation; Microbiome; Prophylaxis; Rifaximin.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antifungal Agents / therapeutic use*
  • Candida / drug effects*
  • Candidiasis / drug therapy*
  • Drug Resistance, Fungal
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Micafungin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Rifaximin / adverse effects
  • Rifaximin / therapeutic use*
  • Risk Factors
  • Transplantation, Homologous / adverse effects

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Rifaximin
  • Micafungin