TY - JOUR
T1 - Alterations of the Oral Microbiome and Cumulative Carbapenem Exposure Are Associated With Stenotrophomonas maltophilia Infection in Patients With Acute Myeloid Leukemia Receiving Chemotherapy
AU - Aitken, Samuel L.
AU - Sahasrabhojane, Pranoti V.
AU - Kontoyiannis, Dimitrios P.
AU - Savidge, Tor C.
AU - Arias, Cesar A.
AU - Ajami, Nadim J.
AU - Shelburne, Samuel A.
AU - Galloway-Peña, Jessica R.
N1 - Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH; R01 AI134637, R21 AI143229, and K24 AI121296 to C. A. A.; U01 AI124290 to T. C. S.; K01 AI143881-01 to J. G. P.), the National Institute of Diabetes and Digestive and Kidney Disease at the NIH (P30 DK56338) to T. C. S., the MD Anderson Odyssey Fellowship Program (to J. G. P.), the CFP Foundation (to J. G. P.), the UTHealth Presidential Award (to C. A. A.), the University of Texas STARS Award (to C. A. A.), and the Texas Medical Center Health Policy Institute Funding Program (to C. A. A.).
Funding Information:
support. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH; R01 AI134637, R21 AI143229, and K24 AI121296 to C. A. A.; U01 AI124290 to T. C. S.; K01 AI143881-01 to J. G. P.), the National Institute of Diabetes and Digestive and Kidney Disease at the NIH (P30 DK56338) to T. C. S., the MD Anderson Odyssey Fellowship Program (to J. G. P.), the CFP Foundation (to J. G. P.), the UTHealth Presidential Award (to C. A. A.), the University of Texas STARS Award (to C. A. A.), and the Texas Medical Center Health Policy Institute Funding Program (to C. A. A.).
Publisher Copyright:
© 2020 The Author(s) 2020.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2021/5/1
Y1 - 2021/5/1
N2 - BACKGROUND: Stenotrophomonas maltophilia is increasingly common in patients with acute myeloid leukemia (AML). Little is known about factors that drive S. maltophilia infection. We evaluated the microbiome and cumulative antibiotic use as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC).METHODS: Subanalysis of a prospective, observational cohort of patients with AML receiving RIC between September 2013 and August 2015 was performed. Fecal and oral microbiome samples collected from initiation 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; and 7/8 (88%) patients with S. maltophilia infection had detectable levels of Stenotrophomonas vs 22/82 (27%) without infection (P < .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, 1.17; 95% confidence interval, 1.01-1.35; P = .03).CONCLUSIONS: Here, 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 monitoring of the oral cavity might identify patients at risk for S. maltophilia infection.
AB - BACKGROUND: Stenotrophomonas maltophilia is increasingly common in patients with acute myeloid leukemia (AML). Little is known about factors that drive S. maltophilia infection. We evaluated the microbiome and cumulative antibiotic use as predictors of S. maltophilia infection in AML patients receiving remission induction chemotherapy (RIC).METHODS: Subanalysis of a prospective, observational cohort of patients with AML receiving RIC between September 2013 and August 2015 was performed. Fecal and oral microbiome samples collected from initiation 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; and 7/8 (88%) patients with S. maltophilia infection had detectable levels of Stenotrophomonas vs 22/82 (27%) without infection (P < .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, 1.17; 95% confidence interval, 1.01-1.35; P = .03).CONCLUSIONS: Here, 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 monitoring of the oral cavity might identify patients at risk for S. maltophilia infection.
KW - bacteremia
KW - colonization
KW - meropenem
KW - pneumonia
KW - risk factors
KW - Stenotrophomonas maltophilia
KW - Prospective Studies
KW - Carbapenems/therapeutic use
KW - Humans
KW - RNA, Ribosomal, 16S/genetics
KW - Gram-Negative Bacterial Infections/epidemiology
KW - Microbiota
KW - Leukemia, Myeloid, Acute/complications
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U2 - 10.1093/cid/ciaa778
DO - 10.1093/cid/ciaa778
M3 - Article
C2 - 32544947
AN - SCOPUS:85097461855
SN - 1058-4838
VL - 72
SP - 1507
EP - 1513
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 9
ER -