The microbiome in hematopoietic stem cell transplant recipients and cancer patients: Opportunities for clinical advances that reduce infection

Why do cancer and stem cell transplant patients develop invasive bacterial and fungal infections?In the 1960s, combination chemotherapy (using cytotoxic agents with different mechanisms of action) was adopted to treat cancer patients, resulting in much higher cure rates.During this time, however, a substantial proportion of cancer patients developed bacterial bloodstream infections, predominantly with gram-negative organisms such as Pseudomonas aeruginosa and Escherichia coli, and the morbidity and mortality associated with these infections was striking.Ironically, these pathogens originated from the patient's own gastrointestinal (GI) tract, based originally on autopsy results and later using molecular studies [1, 2].In particular, those patients with severe neutropenia (absolute neutrophil count <100 cells/mm 3 ) and fever were found to be at highest risk for developing bacterial and fungal bloodstream infections.These findings led to sweeping changes in clinical practice whereby initiation of empiric antibiotics for cancer patients with fever and neutropenia became and continues to be standard of care and had a remarkable effect on decreasing the morbidity and mortality associated with these infections [3].These patients are often admitted for inpatient hospitalization and maintained on antibiotics until the fever has resolved and the neutrophil count has recovered (>500 cells/mm 3 ).While treating febrile and neutropenic patients with antibiotics is standard of care, the choice of which antibiotic(s) to use is still largely institution dependent, as a number of antibiotics have been shown to be efficacious in this setting.Thus, cancer and stem cell transplant (SCT) patients often receive multiple antibiotics for long durations of time, and many patients never have a laboratory-documented infection.Cessation of empiric antibiotics before neutrophil recovery, however, is associated with an increased risk of infection [4].While countless lives have been saved by this practice, clinicians are now facing an increasing number of antibiotic-resistant bacteria in these patients [5].Furthermore, recent studies have now shown that cancer and SCT patients with significant disruptions in gut microbiota communities are at increased risk for developing invasive infections [2] and the posttransplant complication known as graft-versus-host disease (GVHD) [6][7][8].In fact, specific antibiotic therapies, particularly those that destroy specific anaerobic commensal communities, appear to be linked to the development of these complications [5,[8][9][10].These data suggest that new, antibiotic-independent approaches to prevent or treat invasive microbial infections in these patients are needed.