Alterations of the oral microbiome and cumulative carbapenem exposure are associated with Stenotrophomonas maltophilia infection in patients with acute myeloid leukemia receiving chemotherapy.

BACKGROUND Stenotrophomonas maltophilia is increasingly common in patients with acute myeloid leukemia (AML). Relatively little is known about factors that drive S. maltophilia infection. We evaluated the utility of the microbiome and cumulative antibiotic use as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC). METHODS We performed a sub-analysis of a prospective, observational cohort of patients with AML receiving RIC between 9/2013 and 8/2015. Fecal and oral microbiome samples collected from the start of RIC until neutrophil recovery were assessed for the relative abundance of Stenotrophomonas via 16S rRNA gene quantitation. The primary outcome, microbiologically-proven S. maltophilia infection, was analyzed using a time-varying Cox proportional hazards model. RESULTS Of 90 included patients, 8 (9%) developed S. maltophilia infection (pneumonia, n=6; skin/soft-tissue, n=2). 4/8 (50%) patients were bacteremic. 7/8 (88%) patients with S. maltophilia infection had detectable levels of Stenotrophomonas vs 22/82 (27%) without infection (p < 0.01). An oral Stenotrophomonas relative abundance of 36% predicted infection (sensitivity: 96%, specificity 93%). No association of S. maltophilia infection with fecal relative abundance was found. Cumulative meropenem exposure was associated with increased infection risk (hazard ratio [HR] 1.17, 95% CI 1.01 - 1.35, p = 0.03). CONCLUSIONS Herein, we identify the oral microbiome as a potential source for S. maltophilia infection and highlight cumulative carbapenem use as a risk factor for S. maltophilia in leukemia patients. These data suggest that real-time molecular monitoring of the oral cavity might identify patients at high risk for S. maltophilia infection.