S. maltophilia infections are increasingly common in patients with acute myeloid leukemia (AML) and associated with high mortality. S. maltophilia is a frequent colonizer in AML patients but relatively little is known about factors that drive S. maltophilia infection. We sought to evaluate the utility of cumulative antibiotic use and the microbiome as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC).
We performed a subanalysis of a prospective, observational cohort study between September 2013 and August 2015 of adult patients with AML receiving RIC. In this study, fecal and oral microbiome samples collected every 96 hours from the start of RIC until neutrophil recovery were assessed for the relative abundance of S. maltophilia via 16s rRNA quantitation. The primary outcome, microbiologically proven S. maltophilia infection, was analyzed using a time-varying Cox proportional hazards model accounting for S. maltophilia relative abundance and cumulative antibiotic exposure. Patients were censored at neutrophil recovery or death.
90 patient were included; of whom, 8 (9%) developed S. maltophilia infection (pneumonia, n = 6; skin/soft-tissue infection, n = 2). 4/8 (50%) patients were bacteremic. 7/8 (88%) patients with S. maltophilia infection had detectable oral 16s oral reads mapping to S. maltophilia vs 22/82 (27%) without infection (P < 0.01). An oral S. maltophilia relative abundance of 36% predicted infection (sensitivity: 96%, specificity 93%, likelihood ratio +: 17.08). No association of S. maltophilia infection with the fecal relative abundance was seen. Cumulative meropenem exposure was associated with increased infection risk (hazard ratio [HR] 1.17, 95% CI 1.01 1.35, P = 0.03), while levofloxacin was associated with decreased infection risk (HR 0.83, 95% CI 0.66 1.04, P = 0.10).
The oral microbiome may play an important role in S. maltophilia pathogenesis in AML patients. Cumulative antibiotic exposure likely modifies S. maltophilia infection risk. These data suggest that real-time molecular monitoring of the oral cavity for S. maltophilia in AML patients could identify patients at high risk for S. maltophilia infection and improve targeted therapy.
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.