Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

•We studied effect of antibiotic exposure on respiratory virus disease post-transplant.•Antibiotic exposure pre- and post-transplant was common before viral onset.•Cumulative antibiotic exposure was a risk factor for respiratory disease progression. Cumulative incidence of lower respiratory tract disease stratified by antibiotic exposure before respiratory viral infection. Recent publications note an association between antibiotic exposure and respiratory viral infections (RVIs). Antibiotics affect microbiota and impair immune response against RVIs in mice, and low microbiome diversity is associated with pulmonary complications including viral lower respiratory tract disease (LRTD) in hematopoietic cell transplantation (HCT) recipients. In this study, we examined whether antibiotic exposure was associated with increased risk of disease progression in RVIs post-transplantation. We analyzed patients who underwent allogeneic HCT (June 2008 to February 2016) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV), or human metapneumovirus (MPV) during the initial 100 days post-transplantation. Antibiotic exposure in the 3 weeks before RVI onset was defined as (1) use of specific antibiotics versus none of these antibiotics and (2) number of antibiotic-days. Cox proportional hazards models were used to examine associations between antibiotic exposures and risk of viral disease progression to proven/probable/possible LRTD. Ninety HCT recipients (84 adults, 6 children) fulfilled study criteria; 33 progressed to LRTD. The number of antibiotic-days was associated with progression to LRTD after adjusting for neutropenia, steroid use, and either lymphopenia (hazard ratio, 1.41 [95% confidence interval, 1.04 to 1.92], P = .027) or monocytopenia (hazard ratio, 1.46 [95% confidence interval, 1.11 to 1.91], P = .006). Specific antibiotic classes was not associated with the outcome. Cumulative antibiotic exposure immediately before RVI onset is a risk factor for disease progression following PIV, RSV, and MPV infections post-transplantation. Larger cohort studies are needed to determine the impact of specific antibiotics or antibiotic classes on disease severity.